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Sample records for natural autoantibody encoded

  1. A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes

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    Miller, D.J.; Rodriguez, M. [Mayo Clinic and Foundation, Rochester, MN (United States)

    1995-03-01

    Antibodies directed against self-Ags are frequently considered detrimental, and have been shown to play a pathogenic role in certain autoimmune diseases. However, the presence of autoreactive Abs in normal individuals suggests that some autoantibodies could participate in normal physiology. Our previous studies demonstrated that monoclonal autoantibodies SCH94.03 and SCH94.32, generated from the splenocytes of uninfected SJL/J mice injected with normal homogenized spinal cord, promote central nervous system remyelination when passively transferred into syngeneic mice chronically infected with Theiler`s murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we show that these two monoclonal autoantibodies are identical, and have phenotypic characteristics of natural autoantibodies. By using a solid phase assay system, SCH94.03 and SCH94.32 showed reactivity toward several protein Ags and chemical haptens, with prominent reactivity toward spectrin, (4-hydroxy-3-nitrophenyl) acetyl, and fluorescein. Sequence analysis showed that both SCH94.03 and SCH94.32 were encoded by identical germline Ig light chain V{sub K}10/J{sub K}l and heavy chain V23/DFL16.1/J{sub H}2 genes, with no definitive somatic mutations. These results indicate that a natural autoantibody participates in a beneficial physiologic response to central nervous system injury. 60 refs., 7 figs.

  2. Immunoregulation by naturally occurring and disease-associated autoantibodies

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Bendtzen, Klaus

    2012-01-01

    The role of naturally occurring autoantibodies (NAbs) in homeostasis and in disease manifestations is poorly understood. In the present chapter, we review how NAbs may interfere with the cytokine network and how NAbs, through formation of complement-activating immune complexes with soluble self......-receptors on antigen-presenting cells and thereby regulate T-cell activity. Knowledge of the influence of NAbs against cytokines on immune homeostasis is likely to have wide-ranging implications both in understanding pathogenesis and in treatment of many immunoinflammatory disorders, including a number of autoimmune......-stimulating factor, interferon (IFN)-α, IFN-β, IFN-γ, macrophage chemotactic protein-1 and IL-21. NAbs against a variety of other self-antigens have also been reported, and using thyroglobulin as an example we discuss how NAbs are capable of promoting uptake of immune complexes via complement receptors and Fc...

  3. Can natural selection encode Bayesian priors?

    Science.gov (United States)

    Ramírez, Juan Camilo; Marshall, James A R

    2017-08-07

    The evolutionary success of many organisms depends on their ability to make decisions based on estimates of the state of their environment (e.g., predation risk) from uncertain information. These decision problems have optimal solutions and individuals in nature are expected to evolve the behavioural mechanisms to make decisions as if using the optimal solutions. Bayesian inference is the optimal method to produce estimates from uncertain data, thus natural selection is expected to favour individuals with the behavioural mechanisms to make decisions as if they were computing Bayesian estimates in typically-experienced environments, although this does not necessarily imply that favoured decision-makers do perform Bayesian computations exactly. Each individual should evolve to behave as if updating a prior estimate of the unknown environment variable to a posterior estimate as it collects evidence. The prior estimate represents the decision-maker's default belief regarding the environment variable, i.e., the individual's default 'worldview' of the environment. This default belief has been hypothesised to be shaped by natural selection and represent the environment experienced by the individual's ancestors. We present an evolutionary model to explore how accurately Bayesian prior estimates can be encoded genetically and shaped by natural selection when decision-makers learn from uncertain information. The model simulates the evolution of a population of individuals that are required to estimate the probability of an event. Every individual has a prior estimate of this probability and collects noisy cues from the environment in order to update its prior belief to a Bayesian posterior estimate with the evidence gained. The prior is inherited and passed on to offspring. Fitness increases with the accuracy of the posterior estimates produced. Simulations show that prior estimates become accurate over evolutionary time. In addition to these 'Bayesian' individuals, we also

  4. The immune system, natural autoantibodies and general homeostasis in health and disease.

    Science.gov (United States)

    Poletaev, A; Boura, P

    2011-10-01

    It is generally accepted that the destination of the immune system is not only to discriminate between self and non-self but also to mount responses against non-self. During the last decades, it became evident that weak self-reactivity is a necessary condition for immune homeostasis. Natural self reactivity and the internal image created by autoantibodies, participate greatly to the maintenance of homeostasis. Under conditions of increased or altered antigenic pressure, the homeostatic status is disrupted and the organism becomes vulnerable to the emergence of diseases. "Immunculus" is the self-reactive and interconnected entity of the immune system, provided by a complicated network of natural autoantibobies of different specificity, as a mosaic picture. Quantitative changes in each part of the image are related to variations of expression of relative antigens. The immune system takes in account image information from the continuous screening of the antigenic status and compares between presented state and the desired (optimal) one. Substantial and prolonged deviations from the optimal state, triggers the induction of compensatory and reparative processes, aiming to restore molecular and functional homeostasis. So, natural autoimmunity through the ability of natural a-Abs to induce mechanisms of natural and acquired immunity, aims to prevent pathogenic processes and maintain or restore health status.

  5. Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome

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    Fattal, Ittai; Shental, Noam; Ben-Dor, Shifra; Molad, Yair; Gabrielli, Armando; Pokroy-Shapira, Elisheva; Oren, Shirly; Livneh, Avi; Langevitz, Pnina; Zandman-Goddard, Gisele; Sarig, Ofer; Margalit, Raanan; Gafter, Uzi; Domany, Eytan; Cohen, Irun R

    2015-01-01

    In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170 000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome. PMID:26227667

  6. Autoantibodies from patients with systemic lupus erythematosus bind a shared sequence of SmD and Epstein-Barr virus-encoded nuclear antigen EBNA I.

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    Sabbatini, A; Bombardieri, S; Migliorini, P

    1993-05-01

    SmD is one of the small nuclear ribonucleoproteins frequently targeted by autoantibodies in systemic lupus erythematosus. We isolated and characterized the antibodies present in lupus sera that are specific for the C-terminal region of SmD (sequence 95-119). This region is highly homologous to sequence 35-58 of the EBNA I antigen, one of the nuclear antigens induced by infection with Epstein-Barr virus. Antibodies affinity purified over a peptide 95-119 column were able to recognize this sequence in the context of the whole SmD molecule, as they reacted with blotted recombinant SmD. Anti-SmD 95-119 antibodies bound also the EBNA I 35-58 peptide and detected the EBNA I molecule in a total cell extract from Epstein-Barr virus-infected lines. A population of anti-SmD antibodies is, therefore, able to bind an epitope shared by the autoantigen and the viral antigen EBNA I. To investigate the involvement of this shared epitope in the generation of anti-SmD antibodies, we immunized mice with the EBNA I 35-58 peptide. Sera from immunized animals displayed the same pattern of reactivity of spontaneously produced anti-SmD antibodies. They reacted in fact with the EBNA peptide as well as with SmD 95-119 and recombinant SmD. These data suggest that molecular mimicry may play a role in the induction of anti-SmD autoantibodies.

  7. Natural biased coin encoded in the genome determines cell strategy.

    Science.gov (United States)

    Dorri, Faezeh; Mahini, Hamid; Sharifi-Zarchi, Ali; Totonchi, Mehdi; Tusserkani, Ruzbeh; Pezeshk, Hamid; Sadeghi, Mehdi

    2014-01-01

    Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

  8. Nucleases Encoded by Integraded Elements CJIE2 and CJIE4 Inhibit Natural Transformation of Campylobacter Jejuni

    NARCIS (Netherlands)

    Gaasbeek, E.J.; Wagenaar, J.A.; Guilhabert, M.R.; Putten, van J.P.; Parker, C.T.; Wal, van der F.J.

    2010-01-01

    The species Campylobacter jejuni is naturally competent for DNA uptake; nevertheless, nonnaturally transformable strains do exist. For a subset of strains we previously showed that a periplasmic DNase, encoded by dns, inhibits natural transformation in C. jejuni. In the present study, genetic

  9. [Autoantibodies as biomarkers].

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    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

  10. Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4(+) T cells in healthy individuals

    DEFF Research Database (Denmark)

    Nielsen, C H; Leslie, R G; Jepsen, B S

    2001-01-01

    Serum from normal individuals contains substantial amounts of natural antibodies (NA) capable of recognizing self antigens. However, the physiological implications of this autoreactivity remain unclear. We have examined the role of self-reactive NA and complement in mediating the uptake of human...... cells are prerequisites for the proliferation of Tg-reactive CD4(+) T cells, suggesting a novel role for natural autoantibodies and complement in the regulation of autoreactivity under physiological conditions....

  11. Characterization and potential clinical applications of autoantibodies against cytokines

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Hansen, Morten Bagge

    2009-01-01

    Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodo....... There are many ways in which the autoantibodies could be naturally induced, and they have been experimentally induced with ease. Therefore, a new therapeutic concept of inducing cytokine autoantibodies via anti-cytokine vaccination is currently rapidly emerging....

  12. Autoantibodies in Neuropsychiatric Disorders

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    Carolin Hoffmann

    2016-04-01

    Full Text Available Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-d-aspartate receptor (NMDA-R, which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition. In recent years, a wide range of neuropsychiatric diseases and autoantibodies targeting ion-channels or neuronal receptors including NMDA-R, voltage gated potassium channel complex (VGKC complex, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R, γ-aminobutyric acid receptor (GABA-R and dopamine receptor (DR were studied and conflicting reports have been published regarding the seroprevalence of these autoantibodies. A clear causative role of autoantibodies on psychiatric symptoms has as yet only been shown for the NMDA-R. Several other autoantibodies have been related to the presence of certain symptoms and antibody effector mechanisms have been proposed. However, extensive clinical studies with large multicenter efforts to standardize diagnostic procedures for autoimmune etiology and animal studies are needed to confirm the pathogenicity of these autoantibodies. In this review, we discuss the current knowledge of neuronal autoantibodies in the major neuropsychiatric disorders: psychotic, major depression, autism spectrum, obsessive-compulsive and attention-deficit/hyperactivity disorders.

  13. Encoding of natural sounds at multiple spectral and temporal resolutions in the human auditory cortex.

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    Roberta Santoro

    2014-01-01

    Full Text Available Functional neuroimaging research provides detailed observations of the response patterns that natural sounds (e.g. human voices and speech, animal cries, environmental sounds evoke in the human brain. The computational and representational mechanisms underlying these observations, however, remain largely unknown. Here we combine high spatial resolution (3 and 7 Tesla functional magnetic resonance imaging (fMRI with computational modeling to reveal how natural sounds are represented in the human brain. We compare competing models of sound representations and select the model that most accurately predicts fMRI response patterns to natural sounds. Our results show that the cortical encoding of natural sounds entails the formation of multiple representations of sound spectrograms with different degrees of spectral and temporal resolution. The cortex derives these multi-resolution representations through frequency-specific neural processing channels and through the combined analysis of the spectral and temporal modulations in the spectrogram. Furthermore, our findings suggest that a spectral-temporal resolution trade-off may govern the modulation tuning of neuronal populations throughout the auditory cortex. Specifically, our fMRI results suggest that neuronal populations in posterior/dorsal auditory regions preferably encode coarse spectral information with high temporal precision. Vice-versa, neuronal populations in anterior/ventral auditory regions preferably encode fine-grained spectral information with low temporal precision. We propose that such a multi-resolution analysis may be crucially relevant for flexible and behaviorally-relevant sound processing and may constitute one of the computational underpinnings of functional specialization in auditory cortex.

  14. Neural Encoding and Decoding with Deep Learning for Dynamic Natural Vision.

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    Wen, Haiguang; Shi, Junxing; Zhang, Yizhen; Lu, Kun-Han; Cao, Jiayue; Liu, Zhongming

    2017-10-20

    Convolutional neural network (CNN) driven by image recognition has been shown to be able to explain cortical responses to static pictures at ventral-stream areas. Here, we further showed that such CNN could reliably predict and decode functional magnetic resonance imaging data from humans watching natural movies, despite its lack of any mechanism to account for temporal dynamics or feedback processing. Using separate data, encoding and decoding models were developed and evaluated for describing the bi-directional relationships between the CNN and the brain. Through the encoding models, the CNN-predicted areas covered not only the ventral stream, but also the dorsal stream, albeit to a lesser degree; single-voxel response was visualized as the specific pixel pattern that drove the response, revealing the distinct representation of individual cortical location; cortical activation was synthesized from natural images with high-throughput to map category representation, contrast, and selectivity. Through the decoding models, fMRI signals were directly decoded to estimate the feature representations in both visual and semantic spaces, for direct visual reconstruction and semantic categorization, respectively. These results corroborate, generalize, and extend previous findings, and highlight the value of using deep learning, as an all-in-one model of the visual cortex, to understand and decode natural vision. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  16. Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4(+) T cells in healthy individuals

    DEFF Research Database (Denmark)

    Nielsen, C H; Leslie, R G; Jepsen, B S

    2001-01-01

    Serum from normal individuals contains substantial amounts of natural antibodies (NA) capable of recognizing self antigens. However, the physiological implications of this autoreactivity remain unclear. We have examined the role of self-reactive NA and complement in mediating the uptake of human...... thyroglobulin (Tg) by human peripheral B cells in reconstituted whole blood. Significant binding of fluorescein isothiocyanate-conjugated-Tg to B cells was observed, and absorption of Tg-reactive antibodies from serum markedly reduced this uptake, as did inactivation of serum complement or blockade...... cells are prerequisites for the proliferation of Tg-reactive CD4(+) T cells, suggesting a novel role for natural autoantibodies and complement in the regulation of autoreactivity under physiological conditions....

  17. Autoantibodies in cryptogenic fibrosing alveolitis

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    du Bois Ron

    2001-02-01

    Full Text Available Abstract The pathogenesis of cryptogenic fibrosing alveolitis (CFA involves injury, an immune/inflammatory response and fibrosis. The cause of the injury is unknown, but the identification of serum autoantibodies makes an autoimmune aetiology attractive. The core study on which this commentary is based used novel cloning and serum screening technologies in order to identify new public and private autoantibodies in sera from 12 patients with CFA. Largely negative conclusions were drawn from that study. However, we suggest that the prevalence of autoantibodies may have been underestimated, that the study was timely and that this approach is worth pursuing further.

  18. Pemphigus vulgaris autoantibody profiling by proteomic technique.

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    Mina Kalantari-Dehaghi

    Full Text Available Pemphigus vulgaris (PV is a mucocutaneous blistering disease characterized by IgG autoantibodies against the stratified squamous epithelium. Current understanding of PV pathophysiology does not explain the mechanism of acantholysis in patients lacking desmoglein antibodies, which justifies a search for novel targets of pemphigus autoimmunity. We tested 264 pemphigus and 138 normal control sera on the multiplexed protein array platform containing 701 human genes encompassing many known keratinocyte cell-surface molecules and members of protein families targeted by organ-non-specific PV antibodies. The top 10 antigens recognized by the majority of test patients' sera were proteins encoded by the DSC1, DSC3, ATP2C1, PKP3, CHRM3, COL21A1, ANXA8L1, CD88 and CHRNE genes. The most common combinations of target antigens included at least one of the adhesion molecules DSC1, DSC3 or PKP3 and/or the acetylcholine receptor CHRM3 or CHRNE with or without the MHC class II antigen DRA. To identify the PV antibodies most specific to the disease process, we sorted the data based on the ratio of patient to control frequencies of antigen recognition. The frequency of antigen recognition by patients that exceeded that of control by 10 and more times were the molecules encoded by the CD33, GP1BA, CHRND, SLC36A4, CD1B, CD32, CDH8, CDH9, PMP22 and HLA-E genes as well as mitochondrial proteins encoded by the NDUFS1, CYB5B, SOD2, PDHA1 and FH genes. The highest specificity to PV showed combinations of autoantibodies to the calcium pump encoded by ATP2C1 with C5a receptor plus DSC1 or DSC3 or HLA-DRA. The results identified new targets of pemphigus autoimmunity. Novel autoantibody signatures may help explain individual variations in disease severity and treatment response, and serve as sensitive and specific biomarkers for new diagnostic assays in PV patients.

  19. Pemphigus Vulgaris Autoantibody Profiling by Proteomic Technique

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    Kalantari-Dehaghi, Mina; Anhalt, Grant J.; Camilleri, Michael J.; Chernyavsky, Alex I.; Chun, Sookhee; Felgner, Philip L.; Jasinskas, Algis; Leiferman, Kristin M.; Liang, Li; Marchenko, Steve; Nakajima-Sasaki, Rie; Pittelkow, Mark R.; Zone, John J.; Grando, Sergei A.

    2013-01-01

    Pemphigus vulgaris (PV) is a mucocutaneous blistering disease characterized by IgG autoantibodies against the stratified squamous epithelium. Current understanding of PV pathophysiology does not explain the mechanism of acantholysis in patients lacking desmoglein antibodies, which justifies a search for novel targets of pemphigus autoimmunity. We tested 264 pemphigus and 138 normal control sera on the multiplexed protein array platform containing 701 human genes encompassing many known keratinocyte cell-surface molecules and members of protein families targeted by organ-non-specific PV antibodies. The top 10 antigens recognized by the majority of test patients’ sera were proteins encoded by the DSC1, DSC3, ATP2C1, PKP3, CHRM3, COL21A1, ANXA8L1, CD88 and CHRNE genes. The most common combinations of target antigens included at least one of the adhesion molecules DSC1, DSC3 or PKP3 and/or the acetylcholine receptor CHRM3 or CHRNE with or without the MHC class II antigen DRA. To identify the PV antibodies most specific to the disease process, we sorted the data based on the ratio of patient to control frequencies of antigen recognition. The frequency of antigen recognition by patients that exceeded that of control by 10 and more times were the molecules encoded by the CD33, GP1BA, CHRND, SLC36A4, CD1B, CD32, CDH8, CDH9, PMP22 and HLA-E genes as well as mitochondrial proteins encoded by the NDUFS1, CYB5B, SOD2, PDHA1 and FH genes. The highest specificity to PV showed combinations of autoantibodies to the calcium pump encoded by ATP2C1 with C5a receptor plus DSC1 or DSC3 or HLA-DRA. The results identified new targets of pemphigus autoimmunity. Novel autoantibody signatures may help explain individual variations in disease severity and treatment response, and serve as sensitive and specific biomarkers for new diagnostic assays in PV patients. PMID:23505434

  20. Autoantibodies in primary sclerosing cholangitis

    OpenAIRE

    Hov, Johannes Roksund; Boberg, Kirsten Muri; Karlsen, Tom H

    2008-01-01

    The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patients, but the specificity of these antibodies is generally low, and the frequencies vary largely between different studies. The presence of autoantibodies in PSC may be the result of a nonspecific dysregulation of the immune system, but the literature in PSC points to the possible...

  1. A DNase encoded by integrated element CJIE1 inhibits natural transformation of Campylobacter jejuni

    NARCIS (Netherlands)

    Gaasbeek, E.J.; Wagenaar, J.A.; Guilhabert, M.R.; Wösten, M.M.S.M.; Putten, van J.P.M.; Graaf-van Bloois, van der L.; Parker, C.T.; Wal, van der F.J.

    2009-01-01

    The species Campylobacter jejuni (C. jejuni) is considered naturally competent for DNA uptake and displays strong genetic diversity. Nevertheless, non-naturally transformable strains and several relatively stable clonal lineages exist. In the present study, the molecular mechanism responsible for

  2. Autoantibody profiling in APS.

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    Roggenbuck, D; Somma, V; Schierack, P; Borghi, M O; Meroni, P L

    2014-10-01

    The international consensus for the classification of antiphospholipid syndrome (APS) requires clinical and laboratory criteria to be considered at an equal level for diagnosing APS. Thus, detection of antiphospholipid antibodies (aPL) being a hallmark of APS has been the object of intensive investigation over the past 40 years. However, appropriate detection of aPL still remains a laboratory challenge due to their heterogeneity comprising autoantibodies reactive to different phospholipid-binding plasma proteins, such as beta-2 glycoprotein I (β2GPI) and prothrombin. The relevance of aPL interacting with phospholipids other than cardiolipin (CL, diphosphatidylglycerol), such as phosphatidylserine (PS), remains elusive with regard to the diagnosis of APS. Recently, the concept of aPL profiling has been introduced to assess the risk of thrombotic complications in patients with APS. New assay techniques, apart from enzyme-linked immunosorbent assays (ELISAs) recommended by the international consensus for the classification of APS, have been proposed for multiplexing of aPL testing. Line immunoassays (LIAs) employing a novel hydrophobic solid phase for the simultaneous detection of different aPL seem to be an intriguing alternative. We evaluated a novel multiplex LIA employing a hydrophobic membrane coated with different phospholipid (PL)-binding proteins or PLs. The performance characteristics of this new multiplexing assay technique demonstrated its usefulness for aPL profiling. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. Mechanisms of Autoantibody-Induced Pathology

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    Ralf J. Ludwig

    2017-05-01

    Full Text Available Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves’ disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. Pathways leading to autoantibody-induced pathology greatly differ among different diseases, and autoantibodies directed against the same antigen, depending on the targeted epitope, can have diverse effects. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects. According to our algorithm, autoantibodies can be classified into the following categories: (1 mimic receptor stimulation, (2 blocking of neural transmission, (3 induction of altered signaling, triggering uncontrolled (4 microthrombosis, (5 cell lysis, (6 neutrophil activation, and (7 induction of inflammation. These mechanisms in relation to disease, as well as principles of autoantibody generation and detection, are reviewed herein.

  4. Mechanisms of Autoantibody-Induced Pathology

    Science.gov (United States)

    Ludwig, Ralf J.; Vanhoorelbeke, Karen; Leypoldt, Frank; Kaya, Ziya; Bieber, Katja; McLachlan, Sandra M.; Komorowski, Lars; Luo, Jie; Cabral-Marques, Otavio; Hammers, Christoph M.; Lindstrom, Jon M.; Lamprecht, Peter; Fischer, Andrea; Riemekasten, Gabriela; Tersteeg, Claudia; Sondermann, Peter; Rapoport, Basil; Wandinger, Klaus-Peter; Probst, Christian; El Beidaq, Asmaa; Schmidt, Enno; Verkman, Alan; Manz, Rudolf A.; Nimmerjahn, Falk

    2017-01-01

    Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves’ disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. Pathways leading to autoantibody-induced pathology greatly differ among different diseases, and autoantibodies directed against the same antigen, depending on the targeted epitope, can have diverse effects. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects. According to our algorithm, autoantibodies can be classified into the following categories: (1) mimic receptor stimulation, (2) blocking of neural transmission, (3) induction of altered signaling, triggering uncontrolled (4) microthrombosis, (5) cell lysis, (6) neutrophil activation, and (7) induction of inflammation. These mechanisms in relation to disease, as well as principles of autoantibody generation and detection, are reviewed herein. PMID:28620373

  5. Encoding of natural sounds at multiple spectral and temporal resolutions in the human auditory cortex

    NARCIS (Netherlands)

    Santoro, Roberta; Moerel, Michelle; De Martino, Federico; Goebel, R.; Ugurbil, Kamil; Yacoub, Essa; Formisano, Elia

    Functional neuroimaging research provides detailed observations of the response patterns that natural sounds (e.g. human voices and speech, animal cries, environmental sounds) evoke in the human brain. The computational and representational mechanisms underlying these observations, however, remain

  6. Antinuclear human autoantibodies as markers in Nicotiana tabacum pollen tubes

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    C. Poggialini

    2014-01-01

    Full Text Available In the present paper we report on the use of antinuclear human autoantibodies as specific markers in Nicotiana tabacum pollen tubes. The antibodies have been tested by fluorescence techniques using a confocal laser scanning microscope. All the antibodies showed specifc labelling pattern and the results, although preliminary in nature, could open new perspectives of research.

  7. Several genes encoding enzymes with the same activity are necessary for aerobic fungal degradation of cellulose in nature.

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    Peter K Busk

    Full Text Available The cellulose-degrading fungal enzymes are glycoside hydrolases of the GH families and lytic polysaccharide monooxygenases. The entanglement of glycoside hydrolase families and functions makes it difficult to predict the enzymatic activity of glycoside hydrolases based on their sequence. In the present study we further developed the method Peptide Pattern Recognition to an automatic approach not only to find all genes encoding glycoside hydrolases and lytic polysaccharide monooxygenases in fungal genomes but also to predict the function of the genes. The functional annotation is an important feature as it provides a direct route to predict function from primary sequence. Furthermore, we used Peptide Pattern Recognition to compare the cellulose-degrading enzyme activities encoded by 39 fungal genomes. The results indicated that cellobiohydrolases and AA9 lytic polysaccharide monooxygenases are hallmarks of cellulose-degrading fungi except brown rot fungi. Furthermore, a high number of AA9, endocellulase and β-glucosidase genes were identified, not in what are known to be the strongest, specialized lignocellulose degraders but in saprophytic fungi that can use a wide variety of substrates whereas only few of these genes were found in fungi that have a limited number of natural, lignocellulotic substrates. This correlation suggests that enzymes with different properties are necessary for degradation of cellulose in different complex substrates. Interestingly, clustering of the fungi based on their predicted enzymes indicated that Ascomycota and Basidiomycota use the same enzymatic activities to degrade plant cell walls.

  8. Using an Insect Mushroom Body Circuit to Encode Route Memory in Complex Natural Environments.

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    Paul Ardin

    2016-02-01

    Full Text Available Ants, like many other animals, use visual memory to follow extended routes through complex environments, but it is unknown how their small brains implement this capability. The mushroom body neuropils have been identified as a crucial memory circuit in the insect brain, but their function has mostly been explored for simple olfactory association tasks. We show that a spiking neural model of this circuit originally developed to describe fruitfly (Drosophila melanogaster olfactory association, can also account for the ability of desert ants (Cataglyphis velox to rapidly learn visual routes through complex natural environments. We further demonstrate that abstracting the key computational principles of this circuit, which include one-shot learning of sparse codes, enables the theoretical storage capacity of the ant mushroom body to be estimated at hundreds of independent images.

  9. Autoantibodies in Patients with Fasciolosis

    Directory of Open Access Journals (Sweden)

    M Korkmaz

    2009-07-01

    Full Text Available "nBackground: Antiself humoral immune responses have been detected not only in classical autoimmune dis­eases, but autoantibodies have also been found in sera of patients suffering from chronic parasitic dis­eases. We aimed to investigate the role of fasciolosis as a trigger factor of autoimmune reactivity by searching some anti­bodies related to hepatobiliary systems, in patients with fasciolosis. "nMethods: Thirty-two patients (17 males, 15 females with fasciolosis were included in this case-control study. Anti-nuclear antibodies (ANA Screen (antigen mixture of dsDNA, histones, nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, ribosomal P-proteins, centromere ELISA and single-antigen ELISAs for detection of some antibodies (dsDNA, Anti-M2, Anti- liver-kidney microsomes type 1 (LKM-1 and Myeloperoxidase (MPO were carried out. "nResults: ANA-screen, M-2, LKM-1, MPO and anti-dsDNA positivity were detected with ELISA in 7, 7, 4, 2 and 2 of 32 patients with fasciolosis, consecutively. No statistically significant difference was de­tected for any of the autoantibodies' frequency between patients with fasciolosis and control group. How­ever, autoantibody positivity rate was significantly higher in patients with fasciolosis (50 % than control group (12.5 %. Absorbance values of all autoantibodies in patients with fasciolosis were statistically sig­nificant higher than controls. "nConclusion: These results lent support to the role of fasciolosis as a trigger factor of autoimmune reactiv­ity by the breakdown of tolerance. In spite of the extensive knowledge that has accumulated, the specific relationship be­tween fasciolosis and autoimmunity is still obscure.

  10. Advances in Computer-Based Autoantibodies Analysis

    Science.gov (United States)

    Soda, Paolo; Iannello, Giulio

    Indirect Immunofluorescence (IIF) imaging is the recommended me-thod to detect autoantibodies in patient serum, whose common markers are antinuclear autoantibodies (ANA) and autoantibodies directed against double strand DNA (anti-dsDNA). Since the availability of accurately performed and correctly reported laboratory determinations is crucial for the clinicians, an evident medical demand is the development of Computer Aided Diagnosis (CAD) tools supporting physicians' decisions.

  11. PEP1 of Arabis alpina is encoded by two overlapping genes that contribute to natural genetic variation in perennial flowering.

    Directory of Open Access Journals (Sweden)

    Maria C Albani

    Full Text Available Higher plants exhibit a variety of different life histories. Annual plants live for less than a year and after flowering produce seeds and senesce. By contrast perennials live for many years, dividing their life cycle into episodes of vegetative growth and flowering. Environmental cues control key check points in both life histories. Genes controlling responses to these cues exhibit natural genetic variation that has been studied most in short-lived annuals. We characterize natural genetic variation conferring differences in the perennial life cycle of Arabis alpina. Previously the accession Pajares was shown to flower after prolonged exposure to cold (vernalization and only for a limited period before returning to vegetative growth. We describe five accessions of A. alpina that do not require vernalization to flower and flower continuously. Genetic complementation showed that these accessions carry mutant alleles at PERPETUAL FLOWERING 1 (PEP1, which encodes a MADS box transcription factor orthologous to FLOWERING LOCUS C in the annual Arabidopsis thaliana. Each accession carries a different mutation at PEP1, suggesting that such variation has arisen independently many times. Characterization of these alleles demonstrated that in most accessions, including Pajares, the PEP1 locus contains a tandem arrangement of a full length and a partial PEP1 copy, which give rise to two full-length transcripts that are differentially expressed. This complexity contrasts with the single gene present in A. thaliana and might contribute to the more complex expression pattern of PEP1 that is associated with the perennial life-cycle. Our work demonstrates that natural accessions of A. alpina exhibit distinct life histories conferred by differences in PEP1 activity, and that continuous flowering forms have arisen multiple times by inactivation of the floral repressor PEP1. Similar phenotypic variation is found in other herbaceous perennial species, and our results

  12. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult...... to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab...

  13. Immunodeficiency secondary to anti-cytokine autoantibodies

    Science.gov (United States)

    Browne, Sarah K.; Holland, Steven M.

    2011-01-01

    Purpose of review Anti-cytokine autoantibodies are an important and emerging mechanism of disease pathogenesis. We will review the clinical and laboratory features of syndromes in which immunodeficiency is caused by or associated with neutralizing anti-cytokine autoantibodies. Recent findings A growing number of patients have been described who demonstrate unique infectious phenotypes associated with neutralizing autoantibodies that target a particular cytokine known to participate in host defense against the offending organism. Examples include anti-granulocyte macrophage-colony stimulating factor (GM-CSF) autoantibodies and pulmonary alveolar proteinosis; anti-interferon(IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria(NTM); anti-(interleukin)IL-6 autoantibodies and severe staphylococcal skin infection; anti-IL-17A, antiIL-17F or anti-IL-22 autoantibodies in patients with mucocutaneous candidiasis in the setting of both the autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome and in cases of thymoma. Summary Anti-cytokine autoantibodies have manifestations that are diverse, ranging from asymptomatic to life-threatening. These emerging and fascinating causes of acquired immunodeficiency may explain some previously idiopathic syndromes. PMID:20966748

  14. Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Chen, Ning; Sellebjerg, Finn Thorup

    2009-01-01

    and the MBP-induced IgM deposition and cytokine production, indicating that these events were facilitated by autoantibodies recognizing conformational epitopes on MBP. We infer that MBP-elicited TNF-alpha and IL-10 responses are promoted to equal extents by naturally occurring MBP autoantibodies...... and autoantibodies contained in MS sera. However, the latter seem to be more efficient in facilitating the production of IFN-gamma and IL-5....

  15. Identification of the naturally occurring genes encoding carbapenem-hydrolysing oxacillinases from Acinetobacter haemolyticus, Acinetobacter johnsonii, and Acinetobacter calcoaceticus.

    Science.gov (United States)

    Figueiredo, S; Bonnin, R A; Poirel, L; Duranteau, J; Nordmann, P

    2012-09-01

    Carbapenem resistance is increasingly being reported among Acinetobacter species, and results mostly from the expression of acquired carbapenem-hydrolysing oxacillinases (CHDLs). Several Acinetobacter species intrinsically possess chromosomal CHDL genes: Acinetobacter baumannii (bla(OXA-51) ), Acinetobacter radioresistens (bla(OXA-23) ), and Acinetobacter lwoffii (bla(OXA-134) ). We aimed to identify the progenitors of novel CHDL-encoding genes for identification of potential reservoirs. We performed PCR screening using degenerated internal primers designed from a sequence alignment of the known CHDLs (OXA-23, OXA-40, OXA-51, OXA-58, OXA-134, and OXA-143) applied to a collection of 50 Acinetobacter strains belonging to 23 different species. Two strains of Acinetobacter johnsonii, one strain of Acinetobacter calcoaceticus and two strains of Acinetobacter haemolyticus were found to harbour, respectively, the totally novel bla(OXA-211) -like, bla(OXA-213) -like and bla(OXA-214) -like genes. In addition, the complete genomes of those three species available in GenBank, i.e. one A. johnsonii genome, four A. calcoaceticus genomes, and one A. haemolyticus genome, were analysed and found to be positive for the presence of bla(OXA211) -like, bla(OXA-213) -like and bla(OXA-214) -like genes, respectively. The β-lactamases OXA-211, OXA-213 and OXA-214 are diverse, with amino acid identities ranging from 53% to 76%, as compared with the naturally occurring OXA-51-like CHDL from A. baumannii. These β-lactamases showed a peculiar hydrolysis profile, including mostly penicillins and carbapenems. Regarding bla(OXA-23) in A. radioresistens and bla(OXA-134) in A. lwoffii, these genes were not expressed (or expressed at a non-significant level) in their host. Detection of these β-lactamase genes might be used as a useful tool for accurate identification of these Acinetobacter species. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical

  16. Autoantibodies

    Science.gov (United States)

    ... primarily affect a single organ, such as the thyroid in Graves disease or Hashimoto thyroiditis , are often easier to diagnose. People with these disorders frequently have signs and symptoms related to that organ. Disorders due to systemic ...

  17. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley

    2015-11-01

    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  18. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP.

    Directory of Open Access Journals (Sweden)

    Scot E Dowd

    Full Text Available BACKGROUND: Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections. METHODS AND FINDINGS: Using a new bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP approach we have evaluated the bacterial diversity of 40 chronic diabetic foot ulcers from different patients. The most prevalent bacterial genus associated with diabetic chronic wounds was Corynebacterium spp. Findings also show that obligate anaerobes including Bacteroides, Peptoniphilus, Fingoldia, Anaerococcus, and Peptostreptococcus spp. are ubiquitous in diabetic ulcers, comprising a significant portion of the wound biofilm communities. Other major components of the bacterial communities included commonly cultured genera such as Streptococcus, Serratia, Staphylococcus and Enterococcus spp. CONCLUSIONS: In this article, we highlight the patterns of population diversity observed in the samples and introduce preliminary evidence to support the concept of functional equivalent pathogroups (FEP. Here we introduce FEP as consortia of genotypically distinct bacteria that symbiotically produce a pathogenic community. According to this hypothesis, individual members of these communities when they occur alone may not cause disease but when they coaggregate or consort together into a FEP the synergistic effect provides the functional equivalence of well-known pathogens, such as Staphylococcus aureus, giving the biofilm community the factors necessary to maintain chronic biofilm infections

  19. Several genes encoding enzymes with the same activity are necessary for aerobic fungal degradation of cellulose in nature

    DEFF Research Database (Denmark)

    Busk, Peter Kamp; Lange, Mette; Pilgaard, Bo

    2014-01-01

    feature as it provides a direct route to predict function from primary sequence. Furthermore, we used Peptide Pattern Recognition to compare the cellulose-degrading enzyme activities encoded by 39 fungal genomes. The results indicated that cellobiohydrolases and AA9 lytic polysaccharide monooxygenases....... In the present study we further developed the method Peptide Pattern Recognition to an automatic approach not only to find all genes encoding glycoside hydrolases and lytic polysaccharide monooxygenases in fungal genomes but also to predict the function of the genes. The functional annotation is an important...

  20. Autoantibodies in systemic sclerosis: Unanswered questions

    Directory of Open Access Journals (Sweden)

    CRISTIANE eKAYSER

    2015-04-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease characterized by vascular abnormalities, and cutaneous and visceral fibrosis. Serum autoantibodies directed to multiple intracellular antigens are present in more than 95% of patients and are considered a hallmark of SSc. They are helpful biomarkers for the early diagnosis of SSc and are associated with distinctive clinical manifestations. With the advent of more sensitive, multiplexed immunoassays, new and old questions about the relevance of autoantibodies in SSc are emerging. In this review we discuss the clinical relevance of autoantibodies in SSc emphasizing the more recently published data. Moreover, we will summarize recent advances regarding the stability of SSc autoantibodies over the course of disease, whether they are mutually exclusive and their potential roles in the disease pathogenesis.

  1. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

    Science.gov (United States)

    Burska, Agata N.; Hunt, Laura; Strollo, Rocky; Ryan, Brent J.; Vital, Ed; Nissim, Ahuva; Winyard, Paul G.; Emery, Paul; Ponchel, Frederique

    2014-01-01

    Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential. PMID:24782594

  2. Detection of autoantibodies using chemiluminescence technologies.

    Science.gov (United States)

    Mahler, Michael; Bentow, Chelsea; Serra, Josep; Fritzler, Marvin J

    2016-01-01

    Although autoantibody detection methods such as indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) have been available for many years and are still in use the innovation of fast, fully automated instruments using chemiluminescence technology in recent years has led to rapid adoption in autoimmune disease diagnostics. In 2009, BIO-FLASH, a fully automated, random access chemiluminescent analyzer, was introduced, proceeded by the development of the QUANTA Flash chemiluminescent immunoassays (CIA) for autoimmune diagnostics. To summarize the evolution of CIAs for the detection of autoantibodies and to review their performance characteristics. Pubmed was screened for publications evaluating novel QUANTA Flash assays and how they compare to traditional methods for the detection of autoantibodies. In addition, comparative studies presented at scientific meetings were summarized. Several studies were identified that compared the novel CIAs with conventional methods for autoantibody detection. The agreements ranged from moderate to excellent depending on the assay. The studies show how the CIA technology has enhanced the analytical and clinical performance characteristics of many autoantibody assays supporting both diagnosis and follow-up testing. CIA has started to improve the diagnostic testing of autoantibodies as an aid in the diagnosis of a broad range of autoimmune diseases.

  3. Recent advances in dermatomyositis-specific autoantibodies.

    Science.gov (United States)

    Fujimoto, Manabu; Watanabe, Rei; Ishitsuka, Yosuke; Okiyama, Naoko

    2016-11-01

    In dermatomyositis, disease-specific autoantibodies now cover more than 70% of patients. These autoantibodies closely correlate with distinct clinical manifestations. In the past few years, extensive evidence has been accumulated on clinical significance of dermatomyositis-specific autoantibodies including autoantibodies against melanoma differentiation antigen 5 (MDA5), transcriptional intermediary factor 1 (TIF1), nuclear matrix protein 2 (NXP2), and small ubiquitin-like modifier activating enzyme (SAE). Anti-MDA5 antibodies are found with high specificity in clinically amyopathic dermatomyositis presenting rapidly progressive interstitial lung disease (ILD) especially in Asian population. Similar tendency has been reported in the US/Europe, although the frequency of positivity and the type of ILD may differ. Anti-TIF1 antibodies are present in juvenile and adult dermatomyositis patients with close correlation with malignancy in adult population. Anti-NXP2 antibodies share similar phenotype with anti-TIF1 antibodies, except that anti-NXP2 antibodies are associated with calcinosis and severe muscle disease. Although numbers are still small, patients with anti-SAE antibodies tend to present skin disease first and then progress to muscle weakness with systematic symptoms including dysphagia. Moreover, distinct cutaneous manifestations and muscle histopathology findings for each autoantibody have been reported. 'Autoantibody-based classification' of dermatomyositis subsets is now a useful strategy for comprehending the heterogeneous spectrum of dermatomyositis.

  4. The Putative Natural Killer Decoy Early Gene m04 (gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T Cells

    OpenAIRE

    Holtappels, Rafaela; Thomas, Doris; Podlech, Jürgen; Geginat, Gernot; Steffens, Hans-Peter; Reddehase, Matthias J.

    2000-01-01

    Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the “missing self.” The re...

  5. Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

    Science.gov (United States)

    Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

    2016-08-01

    Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

  6. Autoantibodies to iron-binding proteins in pigs infested with Sarcoptes scabiei.

    Science.gov (United States)

    Toet, Hayley M; Fischer, Katja; Mounsey, Kate E; Sandeman, R Mark

    2014-09-15

    Despite the availability of effective treatments, Sarcoptes scabiei remains a major health problem in the pig industry. Unsuccessful control of the disease is often due to the lack of reliable detection methods, with current tests relying on skin scrapings and crude antigen ELISAs. A previous analysis of antigens in pig skin scrapings reported that anti-transferrin antibodies were present in S. scabiei infected animals and that this finding might be considered as a useful diagnostic tool. This paper confirms IgG autoantibodies against transferrin, including the first report of IgM autoantibodies, in both naturally and experimentally infected pigs using ELISA and dot blot assays. Autoantibodies were also detected in pigs to ferritin and to a lesser extent lactoferrin. Immunoblotting confirmed the presence of IgG and IgM autoantibodies in mange positive pigs, as well as IgM antibodies to transferrin and albumin in mange negative pigs. These findings suggest the presence of natural autoantibodies to transferrin and albumin in pigs. The development of the IgG autoimmune response may either be a host mechanism for limiting iron to the mite via antibody mediated clearance, the result of host exposure to mite iron-binding homologues or because of a mite-induced antigenic change to host transferrin. Further investigation into the formation of these autoantibodies may provide insights into the importance of iron in scabies infections and the development and perseverance of S. scabiei infections in pigs. The specificity and sensitivity of the anti-transferrin response reinforces its potential in the diagnosis of scabies in pigs. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides

    Directory of Open Access Journals (Sweden)

    Hiroaki Suga

    2013-03-01

    Full Text Available In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and N-methyl-modified backbones. The complexity of sequence space in such libraries reaches as high as a trillion (>1012, affording initial hits of high affinity ligands against protein targets. Although this article comprehensively covers several related technologies, we discuss in greater detail the technical development and advantages of the Random non-standard Peptide Integration Discovery (RaPID system, including the recent identification of inhibitors against various therapeutic targets.

  8. Molecular and biochemical characterization of the natural chromosome-encoded class A beta-lactamase from Pseudomonas luteola.

    Science.gov (United States)

    Doublet, Benoît; Robin, Frédéric; Casin, Isabelle; Fabre, Laëtitia; Le Fleche, Anne; Bonnet, Richard; Weill, François-Xavier

    2010-01-01

    Pseudomonas luteola (formerly classified as CDC group Ve-1 and named Chryseomonas luteola) is an unusual pathogen implicated in rare but serious infections in humans. A novel beta-lactamase gene, bla(LUT-1), was cloned from the whole-cell DNA of the P. luteola clinical isolate LAM, which had a weak narrow-spectrum beta-lactam-resistant phenotype, and expressed in Escherichia coli. This gene encoded LUT-1, a 296-amino-acid Ambler class A beta-lactamase with a pI of 6 and a theoretical molecular mass of 28.9 kDa. The catalytic efficiency of this enzyme was higher for cephalothin, cefuroxime, and cefotaxime than for penicillins. It was found to be 49% to 59% identical to other Ambler class A beta-lactamases from Burkholderia sp. (PenA to PenL), Ralstonia eutropha (REUT), Citrobacter sedlakii (SED-1), Serratia fonticola (FONA and SFC-1), Klebsiella sp. (KPC and OXY), and CTX-M extended-spectrum beta-lactamases. No gene homologous to the regulatory ampR genes of class A beta-lactamases was found in the vicinity of the bla(LUT-1) gene. The entire bla(LUT-1) coding region was amplified by PCR and sequenced in five other genetically unrelated P. luteola strains (including the P. luteola type strain). A new variant of bla(LUT-1) was found for each strain. These genes (named bla(LUT-2) to bla(LUT-6)) had nucleotide sequences 98.1 to 99.5% identical to that of bla(LUT-1) and differing from this gene by two to four nonsynonymous single nucleotide polymorphisms. The bla(LUT) gene was located on a 700- to 800-kb chromosomal I-CeuI fragment, the precise size of this fragment depending on the P. luteola strain.

  9. Autoantibodies in SLE: Specificities, Isotypes and Receptors

    Directory of Open Access Journals (Sweden)

    Barbara Dema

    2016-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

  10. Autoantibody profile and other immunological parameters in ...

    African Journals Online (AJOL)

    Background: An autoimmune cause and related immunological alterations resulting in recurrent spontaneous abortion (RSA) have been suggested in patients with unknown etiology. Materials and Methods: This study evaluated the autoantibody profile and other immunological parameters among RSA patients and normal ...

  11. Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease

    International Nuclear Information System (INIS)

    Gershenfeld, H.K.; Hershberger, R.J.; Shows, T.B.; Weissman, I.L.

    1988-01-01

    A cDNA clone encoding a human T cell- and natural killer cell-specific serine protease was obtained by screening a phage λgt10 cDNA library from phytohemagglutinin-stimulated human peripheral blood lymphocytes with the mouse Hanukah factor cDNA clone. In an RNA blot-hybridization analysis, this human Hanukah factor cDNA hybridized with a 1.3-kilobase band in allogeneic-stimulated cytotoxic T cells and the Jurkat cell line, but this transcript was not detectable in normal muscle, liver, tonsil, or thymus. By dot-blot hybridization, this cDNA hybridized with RNA from three cytolytic T-cell clones and three noncytolytic T-cell clones grown in vitro as well as with purified CD16 + natural killer cells and CD3 + , CD16 - T-cell large granular lymphocytes from peripheral blood lymphocytes (CD = cluster designation). The nucleotide sequence of this cDNA clone encodes a predicted serine protease of 262 amino acids. The active enzyme is 71% and 77% similar to the mouse sequence at the amino acid and DNA level, respectively. The human and mouse sequences conserve the active site residues of serine proteases--the trypsin-specific Asp-189 and all 10 cysteine residues. The gene for the human Hanukah factor serine protease is located on human chromosome 5. The authors propose that this trypsin-like serine protease may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells

  12. Frequency and levels of autoantibodies in healthy adult Omanis

    International Nuclear Information System (INIS)

    Al-Jabri, Ali A.; A-Belushi Mohammad; Nanze, Herburt

    2003-01-01

    A previous pilot study showed high frequency of anti-smooth muscle autoantibody in Omani blood donors and pregnant women. We conducted this larger-scale study to investigate the frequency and significance of several autoantibodies in healthy individuals from different regions of Oman. Sera obtained from 1537 healthy Omanis (1153 males and 384 females ), ranging in age from 18 to 57 years, tested for the presence of ten different autoantibodies using indirect immunofluoresence, haemagglutination and latex agglutination techniques. Low levels of autoantibodies were detected in 33.5%, whereas a few individuals (1.8%) showed high autoantibody titres. Anti-smooth muscle autoantibodies (ASMA) were the most prevalent (11%). Anti-nuclear autoantibodies (ANA) were the second most prevalent (7.6%). Anti-thyroid microsomal autoantibodies (ATMA) and anti-thyroglobulin autoantibodies (ATA) were present in 6.5% and 4.4% of individuals,respectively. The other autoantibodies were detected much less frequently: anti-parietal cells autoandibodies (APCA) were found in 1.6%,anti-brush border antibodies (ABBA) in 1.3% anti-reticulin autoantibodies (ARA) in 1%, anti-mitochondrial antibodies in 0.8%, antiglomerular basement membrane antibodies (AGBMA) in 0.7% and rheumatoid factor(RF) in 0.4%.Low levels of autoantibodies were detected in 33.5%, whereas a few individuals (1.8%) showed high autoantibody titres. Anti-smooth muscle autoantibodies (ASMA) were the most prevalent (11%). Anti-nuclear autoantibodies (ANA) were the second most prevalent (7.6%). Anti-thyroid microsomal autoantibodies (ATMA) and anti-thyroglobulin autoantibodies (ATA) were present in 6.5% and 4.4% of individuals,respectively. The other autoantibodies were detected much less frequently: anti-parietal cells autoandibodies (APCA) were found in 1.6%,anti-brush border antibodies (ABBA) in 1.3% anti-reticulin autoantibodies (ARA) in 1%, anti-mitochondrial antibodies in 0.8%, antiglomerular basement membrane antibodies

  13. Population genetics and natural selection in the gene encoding the Duffy binding protein II in Iranian Plasmodium vivax wild isolates.

    Science.gov (United States)

    Valizadeh, Vahideh; Zakeri, Sedigheh; Mehrizi, Akram Abouie; Djadid, Navid Dinparast

    2014-01-01

    Region II of Duffy binding protein (PvDBP-II) is one of the most promising blood-stage vaccine candidate antigens against Plasmodium vivax and having knowledge of the nature and genetic polymorphism of PvDBP-II among global P. vivax isolates is important for developing a DBP-based vaccine. By using PCR and sequencing, the present molecular population genetic approach was carried out to investigate sequence diversity and natural selection of dbp-II gene in 63 P. vivax isolates collected from unstable and low transmission malaria-endemic areas of Iran during 2008-2012. Also, phylogenetic analysis, the diversifying natural selection, and recombination across the pvdbp-II gene, including regions containing B-cell epitopes were analyzed using the DnaSP and MEGA4 programs. Twenty two single nucleotide polymorphisms (SNPs, including 20 non-synonymous and 2 synonymous) were identified in PvDBP-II, resulting in 16 different PvDBP-II haplotypes among the Iranian P. vivax isolates. High binding inhibitory B-cell epitope (H3) overlapping with intrinsically unstructured/disordered region (aa: 384-392) appeared to be highly polymorphic (D384G/E385K/ K386N/Q/R390H), and positive selective pressure acted on this region. Most of the polymorphic amino acids, which are located on the surface of the protein, are under selective pressure that implies increased recombination events and exposure to the human immune system. In summary, PvDBP-II gene displays genetic polymorphism among Iranian P. vivax isolates and it is under selective pressure. Mutations, recombination, and positive selection seem to play a role in the resulting genetic diversity, and phylogenetic analysis of DNA sequences demonstrates that Iranian isolates represent a sample of the global population. These results are useful for understanding the nature of the P. vivax population in Iran and also for development of PvDBP-II-based malaria vaccine. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Host Factors Influencing the Retrohoming Pathway of Group II Intron RmInt1, Which Has an Intron-Encoded Protein Naturally Devoid of Endonuclease Activity.

    Directory of Open Access Journals (Sweden)

    Rafael Nisa-Martínez

    Full Text Available Bacterial group II introns are self-splicing catalytic RNAs and mobile retroelements that have an open reading frame encoding an intron-encoded protein (IEP with reverse transcriptase (RT and RNA splicing or maturase activity. Some IEPs carry a DNA endonuclease (En domain, which is required to cleave the bottom strand downstream from the intron-insertion site for target DNA-primed reverse transcription (TPRT of the inserted intron RNA. Host factors complete the insertion of the intron. By contrast, the major retrohoming pathway of introns with IEPs naturally lacking endonuclease activity, like the Sinorhizobium meliloti intron RmInt1, is thought to involve insertion of the intron RNA into the template for lagging strand DNA synthesis ahead of the replication fork, with possible use of the nascent strand to prime reverse transcription of the intron RNA. The host factors influencing the retrohoming pathway of such introns have not yet been described. Here, we identify key candidates likely to be involved in early and late steps of RmInt1 retrohoming. Some of these host factors are common to En+ group II intron retrohoming, but some have different functions. Our results also suggest that the retrohoming process of RmInt1 may be less dependent on the intracellular free Mg2+ concentration than those of other group II introns.

  15. Single Neurons in the Avian Auditory Cortex Encode Individual Identity and Propagation Distance in Naturally Degraded Communication Calls.

    Science.gov (United States)

    Mouterde, Solveig C; Elie, Julie E; Mathevon, Nicolas; Theunissen, Frédéric E

    2017-03-29

    One of the most complex tasks performed by sensory systems is "scene analysis": the interpretation of complex signals as behaviorally relevant objects. The study of this problem, universal to species and sensory modalities, is particularly challenging in audition, where sounds from various sources and localizations, degraded by propagation through the environment, sum to form a single acoustical signal. Here we investigated in a songbird model, the zebra finch, the neural substrate for ranging and identifying a single source. We relied on ecologically and behaviorally relevant stimuli, contact calls, to investigate the neural discrimination of individual vocal signature as well as sound source distance when calls have been degraded through propagation in a natural environment. Performing electrophysiological recordings in anesthetized birds, we found neurons in the auditory forebrain that discriminate individual vocal signatures despite long-range degradation, as well as neurons discriminating propagation distance, with varying degrees of multiplexing between both information types. Moreover, the neural discrimination performance of individual identity was not affected by propagation-induced degradation beyond what was induced by the decreased intensity. For the first time, neurons with distance-invariant identity discrimination properties as well as distance-discriminant neurons are revealed in the avian auditory cortex. Because these neurons were recorded in animals that had prior experience neither with the vocalizers of the stimuli nor with long-range propagation of calls, we suggest that this neural population is part of a general-purpose system for vocalizer discrimination and ranging. SIGNIFICANCE STATEMENT Understanding how the brain makes sense of the multitude of stimuli that it continually receives in natural conditions is a challenge for scientists. Here we provide a new understanding of how the auditory system extracts behaviorally relevant information

  16. Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond.

    Science.gov (United States)

    Xia, Yang; Kellems, Rodney E

    2013-06-21

    Hypertensive disorders are life-threatening diseases with high morbidity and mortality, affecting billions of individuals worldwide. A multitude of underlying conditions may contribute to hypertension, thus the need for a plethora of treatment options to identify the approach that best meets the needs of individual patients. A growing body of evidence indicates that (1) autoantibodies that bind to and activate the major angiotensin II type I (AT₁) receptor exist in the circulation of patients with hypertensive disorders, (2) these autoantibodies contribute to disease pathophysiology, (3) antibody titers correlate to the severity of the disease, and (4) efforts to block or remove these pathogenic autoantibodies have therapeutic potential. These autoantibodies, termed AT₁ agonistic autoantibodies have been extensively characterized in preeclampsia, a life-threatening hypertensive condition of pregnancy. As reviewed here, these autoantibodies cause symptoms of preeclampsia when injected into pregnant mice. Somewhat surprisingly, these auto antibodies also appear in 3 animal models of preeclampsia. However, the occurrence of AT₁ agonistic autoantibodies is not restricted to pregnancy. These autoantibodies are prevalent among kidney transplant recipients who develop severe transplant rejection and malignant hypertension during the first week after transplantation. AT₁ agonistic autoantibodies are also highly abundant among a group of patients with essential hypertension that are refractory to standard therapy. More recently these autoantibodies have been seen in patients with the autoimmune disease, systemic sclerosis. These 3 examples extend the clinical impact of AT₁ agonistic autoantibodies beyond pregnancy. Research reviewed here raises the intriguing possibility that preeclampsia and other hypertensive conditions are autoimmune diseases characterized by the presence of pathogenic autoantibodies that activate the major angiotensin receptor, AT₁. These

  17. Strategies for building reference standards for autoantibodies

    Directory of Open Access Journals (Sweden)

    Joanna eSheldon

    2015-04-01

    Full Text Available Producing robust, certified, traceable reference material for autoantibody testing is a vital element in maintaining the validity of results that are generated in the daily clinical laboratory routine. This is a huge challenge because of the high number of variables involved in the detection and measurement of the autoantibodies. The production of such materials is time consuming and needs rigorous attention to detail; this is best achieved by an overarching independent body who will oversee the process in a not for profit manner.Much effort has been made to build international standards for quantitative and qualitative assays based on monoclonal antibodies, obtained from affinity purification and plasmapheresis. The big challenge is to respect individual differences in immune response to the same antigen. A promising ongoing initiative is the construction of pools with monospecific samples from different individuals.

  18. Muscle autoantibodies in myasthenia gravis: beyond diagnosis?

    Science.gov (United States)

    Meriggioli, Matthew N; Sanders, Donald B

    2012-01-01

    Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. A number of molecules, including ion channels and other proteins at the neuromuscular junction, may be targeted by autoantibodies leading to abnormal neuromuscular transmission. In approximately 85% of patients, autoantibodies, directed against the postsynaptic nicotinic acetylcholine receptor can be detected in the serum and confirm the diagnosis, but in general, do not precisely predict the degree of weakness or response to therapy. Antibodies to the muscle-specific tyrosine kinase are detected in approximately 50% of generalized myasthenia gravis patients who are seronegative for anti-acetylcholine receptor antibodies, and levels of anti-muscle-specific tyrosine kinase antibodies do appear to correlate with disease severity and treatment response. Antibodies to other muscle antigens may be found in the subsets of myasthenia gravis patients, potentially providing clinically useful diagnostic information, but their utility as relevant biomarkers (measures of disease state or response to treatment) is currently unclear. PMID:22882218

  19. Preferential recognition of auto-antibodies against 4-hydroxynonenal modified DNA in the cancer patients.

    Science.gov (United States)

    Faisal, Mohammad; Shahab, Uzma; Alatar, Abdulrahman A; Ahmad, Saheem

    2017-11-01

    The structural perturbations in DNA molecule may be caused by a break in a strand, a missing base from the backbone, or a chemically changed base. These alterations in DNA that occurs naturally can result from metabolic or hydrolytic processes. DNA damage plays a major role in the mutagenesis, carcinogenesis, aging and various other patho-physiological conditions. DNA damage can be induced through hydrolysis, exposure to reactive oxygen species (ROS) and other reactive carbonyl metabolites including 4-hydroxynonenal (HNE). 4-HNE is an important lipid peroxidation product which has been implicated in the mutagenesis and carcinogenesis processes. The present study examines to probe the presence of auto-antibodies against 4-hydroxynonenal damaged DNA (HNE-DNA) in various cancer subjects. In this study, the purified calf thymus DNA was damaged by the action of 4-HNE. The DNA was incubated with 4-HNE for 24 h at 37°C temperature. The binding characteristics of cancer auto-antibodies were assessed by direct binding and competitive inhibition ELISA. DNA modifications produced hyperchromicity in UV spectrum and decreased fluorescence intensity. Cancer sera exhibited enhanced binding with the 4-HNE modified calf thymus DNA as compared to its native conformer. The 4-HNE modified DNA presents unique epitopes which may be one of the factors for the auto-antibody induction in cancer patients. The HNE modified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in cancer patients. © 2017 Wiley Periodicals, Inc.

  20. Characterisation of osteoprotegerin autoantibodies in coeliac disease.

    Science.gov (United States)

    Real, Ana; Gilbert, Nick; Hauser, Barbara; Kennedy, Nick; Shand, Alan; Gillett, Helen; Gillett, Peter; Goddard, Clive; Cebolla, Ángel; Sousa, Carolina; Fraser, William D; Satsangi, Jack; Ralston, Stuart H; Riches, Philip L

    2015-08-01

    Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence and epitope specificity of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density. A direct enzyme-linked immunosorbent assay was developed and used to screen patients with coeliac disease for autoantibodies to OPG. Recombinant fragments of OPG were made to evaluate the epitope specificity and affinity of these antibodies. Phenotype information of the patients was obtained by case note review. Raised titres of antibodies to OPG were found in 7/71 (9.8 %) patients with coeliac disease, compared with 1/72 (1.4 %) non-coeliac osteoporosis clinic control patients (p coeliac disease and are independently associated with lower bone mineral density Z-scores of the hip. Further work is required to establish the clinical utility of testing for OPG antibodies.

  1. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Science.gov (United States)

    Deloumeau, Aude; Bayard, Sophie; Coquerel, Quentin; Déchelotte, Pierre; Bole-Feysot, Christine; Carlander, Bertrand; Cochen De Cock, Valérie; Fetissov, Sergueï O; Dauvilliers, Yves

    2010-10-13

    Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  2. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Aude Deloumeau

    Full Text Available BACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  3. A naturally occurring Lgr4 splice variant encodes a soluble antagonist useful for demonstrating the gonadal roles of Lgr4 in mammals.

    Directory of Open Access Journals (Sweden)

    Pei-Jen Hsu

    Full Text Available Leucine-rich repeat containing G protein-coupled receptor 4 (LGR4 promotes the Wnt signaling through interaction with R-spondins or norrin. Using PCR amplification from rat ovarian cDNAs, we identified a naturally occurring Lgr4 splice variant encoding only the ectodomain of Lgr4, which was named Lgr4-ED. Lgr4-ED can be detected as a secreted protein in the extracts from rodent and bovine postnatal gonads, suggesting conservation of Lgr4-ED in mammals. Recombinant Lgr4-ED purified from the conditioned media of transfected 293T cells was found to dose-dependently inhibit the LGR4-mediated Wnt signaling induced by RSPO2 or norrin, suggesting that it is capable of ligand absorption and could have a potential role as an antagonist. Intraperitoneal injection of purified recombinant Lgr4-ED into newborn mice was found to significantly decrease the testicular expression of estrogen receptor alpha and aquaporin 1, which is similar to the phenotype found in Lgr4-null mice. Administration of recombinant Lgr4-ED to superovulated female rats can also decrease the expression of estrogen receptor alpha, aquaporin 1, LH receptor and other key steroidogenic genes as well as bring about the suppression of progesterone production. Thus, these findings suggest that endogenously expressed Lgr4-ED may act as an antagonist molecule and help to fine-tune the R-spondin/norrin-mediated Lgr4-Wnt signaling during gonadal development.

  4. Overexpression of a natural chloroplast-encoded antisense RNA in tobacco destabilizes 5S rRNA and retards plant growth

    Directory of Open Access Journals (Sweden)

    Stern David B

    2010-09-01

    Full Text Available Abstract Background The roles of non-coding RNAs in regulating gene expression have been extensively studied in both prokaryotes and eukaryotes, however few reports exist as to their roles in organellar gene regulation. Evidence for accumulation of natural antisense RNAs (asRNAs in chloroplasts comes from the expressed sequence tag database and cDNA libraries, while functional data have been largely obtained from artificial asRNAs. In this study, we used Nicotiana tabacum to investigate the effect on sense strand transcripts of overexpressing a natural chloroplast asRNA, AS5, which is complementary to the region which encodes the 5S rRNA and tRNAArg. Results AS5-overexpressing (AS5ox plants obtained by chloroplast transformation exhibited slower growth and slightly pale green leaves. Analysis of AS5 transcripts revealed four distinct species in wild-type (WT and AS5ox plants, and additional AS5ox-specific products. Of the corresponding sense strand transcripts, tRNAArg overaccumulated several-fold in transgenic plants whereas 5S rRNA was unaffected. However, run-on transcription showed that the 5S-trnR region was transcribed four-fold more in the AS5ox plants compared to WT, indicating that overexpression of AS5 was associated with decreased stability of 5S rRNA. In addition, polysome analysis of the transformants showed less 5S rRNA and rbcL mRNA associated with ribosomes. Conclusions Our results suggest that AS5 can modulate 5S rRNA levels, giving it the potential to affect Chloroplast translation and plant growth. More globally, overexpression of asRNAs via chloroplast transformation may be a useful strategy for defining their functions.

  5. Infliximab-induced autoantibodies: a multicenter study.

    Science.gov (United States)

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  6. 21 CFR 866.5660 - Multiple autoantibodies immunological test system.

    Science.gov (United States)

    2010-04-01

    ... the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  7. 21 CFR 866.5870 - Thyroid autoantibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid autoantibody immunological test system...

  8. Anti-IL-1alpha autoantibodies in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Forslind, K; Svensson, Birte; Svenson, M

    2001-01-01

    To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA).......To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA)....

  9. Neural Semantic Encoders.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Yu, Hong

    2017-04-01

    We present a memory augmented neural network for natural language understanding: Neural Semantic Encoders. NSE is equipped with a novel memory update rule and has a variable sized encoding memory that evolves over time and maintains the understanding of input sequences through read , compose and write operations. NSE can also access multiple and shared memories. In this paper, we demonstrated the effectiveness and the flexibility of NSE on five different natural language tasks: natural language inference, question answering, sentence classification, document sentiment analysis and machine translation where NSE achieved state-of-the-art performance when evaluated on publically available benchmarks. For example, our shared-memory model showed an encouraging result on neural machine translation, improving an attention-based baseline by approximately 1.0 BLEU.

  10. The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells.

    Science.gov (United States)

    Holtappels, R; Thomas, D; Podlech, J; Geginat, G; Steffens, H P; Reddehase, M J

    2000-02-01

    Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the "missing self." The retention, however, is counteracted by the m04 early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 might serve to silence NK cells and thereby complete the immune evasion of MCMV. In light of these current views, we provide here results demonstrating an in vivo role for gp34 in protective antiviral immunity. We have identified an antigenic nonapeptide derived from gp34 and presented by the MHC-I molecule D(d). Besides the immunodominant immediate-early nonapeptide consisting of IE1 amino acids 168-176 (IE1(168-176)), the early nonapeptide m04(243-251) is the second antigenic peptide described for MCMV. The primary immune response to MCMV generates significant m04-specific CD8 T-cell memory. Upon adoptive transfer into immunodeficient recipients, an m04-specific CTL line controls MCMV infection with an efficacy comparable to that of an IE1-specific CTL line. Thus, gp34 is the first noted early protein of MCMV that escapes viral immune evasion mechanisms. These data document that MCMV is held in check by a redundance of protective CD8 T cells recognizing antigenic peptides in different phases of viral gene expression.

  11. The role of autoantibodies in the pathophysiology of rheumatoid arthritis.

    Science.gov (United States)

    Derksen, V F A M; Huizinga, T W J; van der Woude, D

    2017-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

  12. Pituitary autoantibodies in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

    Science.gov (United States)

    O'Dwyer, Damien T; McElduff, Patrick; Peterson, Pärt; Perheentupa, Jaakko; Crock, Patricia A

    2007-01-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal recessive disease due to mutations in the AIRE (AutoImmune REgulator) gene. The role of pituitary autoimmunity in APECED is not known. We determined the prevalence of pituitary autoantibodies in a cohort of 67 Finnish patients with APECED from 217 serum samples collected over 26 years by one investigator. Overall, autoantibodies to the 49 kDa cytosolic autoantigen, human pituitary enolase were detected in 39 of the 67 patients (58%). On their first sample, 25 patients had autoantibodies compared to 5 of 68 controls (chi-square, 1df=17.11, pAPECED patients.

  13. [Glycosylation of autoantibodies in autoimmunes diseases].

    Science.gov (United States)

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

    Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. A novel automated indirect immunofluorescence autoantibody evaluation.

    Science.gov (United States)

    Kivity, Shaye; Gilburd, Boris; Agmon-Levin, Nancy; Carrasco, Marina Garcia; Tzafrir, Yaron; Sofer, Yael; Mandel, Matilda; Buttner, Thomas; Roggenbuck, Dirk; Matucci-Cerinic, Marco; Danko, Katalin; Hoyos, Marcos López; Shoenfeld, Yehuda

    2012-03-01

    Autoantibodies (AAb), especially antinuclear (ANAs) and anticytoplasmatic antibodies (ACyA), are essential diagnosing markers for several autoimmune diseases. The current gold standard method for ANA detection is manual indirect immunofluorescence (IIF) on human epithelial-2 (HEp-2) cells. However, this technique is cost and time consuming, and characterized by considerable intra- and interlaboratory variability. Thus, an automated IIF-HEp-2 reader has been developed recently. In the current study, we compared the performance of the automated AAb IIF-HEp-2 interpretation to conventional detection methods. Autoantibody detection by IIF on HEp-2 cells was performed in a total of 260 sera of patients, including 34 with systemic lupus erythematosus, 111 with dermatomyositis or polymyositis, 74 with systemic sclerosis, 41 with rare AAb patterns, and 137 healthy individuals. Visual interpretation and routine immunoassays were compared with a novel automated IIF-HEp-2 system using Aklides pattern recognition algorithms. Positive AAbs were detected in 95-100% of rheumatic patients by automated interpretation, in 74-100% with manual reading, and in 64-100% by immunodot assay. Receiver operating characteristic curve analysis of fluorescent intensity revealed a high sensitivity and specificity for automated reading of AAb with an agreement ranging from 90% to 95% between manual and automated interpretation (kappa 0.554-0.69) for systemic sclerosis and myositis, respectively. This study demonstrates a good correlation between manual and automated interpretation of AAb including ANA and ACyA in patients with autoimmune diseases. Full automation of HEp-2 cell assay reading may minimize errors in ANA pattern interpretation and thus help in the standardization of ANA assessment.

  15. Anti-neutrophil cytoplasm autoantibodies (ANCA) in autoimmune liver diseases

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees

    1999-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes and monocytes. ANCA have been detected in serum from patients with inflammatory bowel diseases (mainly ulcerative colitis) and autoimmune mediated liver diseases

  16. Clinical and Pathological Roles of Ro/SSA Autoantibody System

    Directory of Open Access Journals (Sweden)

    Ryusuke Yoshimi

    2012-01-01

    Full Text Available Anti-Ro/SSA antibodies are among the most frequently detected autoantibodies against extractable nuclear antigens and have been associated with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS. Although the presence of these autoantibodies is one of the criteria for the diagnosis and classification of SS, they are also sometimes seen in other systemic autoimmune diseases. In the last few decades, the knowledge of the prevalence of anti-Ro/SSA antibodies in various autoimmune diseases and symptoms has been expanded, and the clinical importance of these antibodies is increasing. Nonetheless, the pathological role of the antibodies is still poorly understood. In this paper, we summarize the milestones of the anti-Ro/SSA autoantibody system and provide new insights into the association between the autoantibodies and the pathogenesis of autoimmune diseases.

  17. Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies.

    Science.gov (United States)

    Pérez, Dolores; Gilburd, Boris; Cabrera-Marante, Óscar; Martínez-Flores, Jose A; Serrano, Manuel; Naranjo, Laura; Pleguezuelo, Daniel; Morillas, Luis; Shovman, Ora; Paz-Artal, Estela; Shoenfeld, Yehuda; Serrano, Antonio

    2017-06-17

    Early detection of antinuclear antibodies (ANA) in asymptomatic subjects is useful to predict autoimmune diseases years before diagnosis. ANA have been determined by indirect immunofluorescence (IIF) using human epithelial type 2 (HEp-2) cells, which is considered the gold standard technique. Multiplex technology (BioPlex ANA Screen) has been introduced for ANA evaluation in recent years. Nevertheless, concordance between BioPlex and IIF is low and there is no harmonization between both methods for detection of autoantibodies. This study has aimed to clarify the clinical significance of autoantibodies detected by BioPlex ANA Screen in subjects with undiagnosed clinical suspicion of autoimmune disease and to determine the predictive value of autoantibodies detected by BioPlex ANA Screen. A 3-year follow-up study was performed of 411 subjects without a clear diagnosis of autoimmune diseases in whom autoantibodies were detected by BioPlex ANA Screen that were negative by IIF on HEp-2 cells. At 3 years of follow-up, 312 (76%) subjects were positive for autoantibodies by IIF and 99 subjects continued to be negative. A diagnosis of autoimmune disease was found in most of the subjects (87%). BioPlex ANA Screen has greater sensitivity than IIF on HEp-2 cells for autoantibodies detection. Early detection of these antibodies by BioPlex can predict possible development of autoimmune diseases.

  18. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    Science.gov (United States)

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  19. Frequency of Synaptic Autoantibody Accompaniments and Neurological Manifestations of Thymoma.

    Science.gov (United States)

    Zekeridou, Anastasia; McKeon, Andrew; Lennon, Vanda A

    2016-07-01

    Thymoma is commonly recognized in association with paraneoplastic autoimmune myasthenia gravis (MG), an IgG-mediated impairment of synaptic transmission targeting the nicotinic acetylcholine receptor of muscle. Newly identified synaptic autoantibodies may expand the serological profile of thymoma. To investigate the frequency of potentially pathogenic neural synaptic autoantibodies in patients with thymoma. We retrospectively identified patients with histopathologically confirmed thymoma and serum available to test for synaptic autoantibodies (collected 1986-2014) at the Mayo Clinic Neuroimmunology Laboratory. We identified and classified 193 patients with thymoma into 4 groups: (1) lacking neurological autoimmunity (n = 43); (2) isolated MG (n = 98); (3) MG plus additional autoimmune neurological manifestations (n = 26); and (4) neurological autoimmunity other than MG (n = 26). Clinical presentation and serum profile of autoantibodies reactive with molecularly defined synaptic plasma membrane proteins of muscle, peripheral, and central nervous systems. Of the 193 patients with thymoma, mean patient age was 52 years and did not significantly differ by sex (106 women) or group. Myasthenia gravis was the most prevalent clinical manifestation (64%) followed by dysautonomia (16 patients [8%]) and encephalopathy (15 patients [8%]); 164 patients (85%) had at least 1 synaptic autoantibody, and 63 of these patients (38%) had at least 1 more. Muscle acetylcholine receptor was most frequent (78%), followed by ganglionic acetylcholine receptor (20%), voltage-gated Kv1 potassium channel-complex (13%), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (5%). Less frequent were aquaporin-4, voltage-gated Kv1 potassium channel-complex related proteins (leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2), glycine receptor, and γ-aminobutyric acid-A receptor. Synaptic autoantibodies were significantly more frequent in patients

  20. Anti-cytokine autoantibodies in autoimmune diseases

    Science.gov (United States)

    Cappellano, Giuseppe; Orilieri, Elisabetta; Woldetsadik, Abiy D; Boggio, Elena; Soluri, Maria F; Comi, Cristoforo; Sblattero, Daniele; Chiocchetti, Annalisa; Dianzani, Umberto

    2012-01-01

    An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1α in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-γ in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis. PMID:23885320

  1. Autoantibodies and immunoglobulins among atomic bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Akahoshi, Masazumi; Kodama, Kazunori; Shimaoka, Katsutaro; Akiyama, Mitoshi; Carter, R.L.; Yamakido, Michio

    1994-01-01

    The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE. 32 refs., 2 figs., 3 tabs

  2. Biological variation of thyroid autoantibodies and thyroglobulin

    DEFF Research Database (Denmark)

    Jensen, Esther; Petersen, Per Hyltoft; Blaabjerg, Ole

    2007-01-01

    is unknown, we investigated this in fertile women during one complete regular menstrual cycle. METHODS: A total of 24 healthy women (23-46 years) were investigated twice a week between 07:30 and 11:00 h. Antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb), and thyrotropin receptor (TRAb) were...... the upper reference limit of the laboratory (6 had TPOAb >10 kIU/L, 6 had TgAb >20 kIU/L and 1 had TRAb >0.75 IU/L). Eight women had Tg below the lower reference limit, five of whom had elevated TgAb. Variations in the thyroid antibodies were random and not related to the menstrual cycle. For TPOAb (2......: It is possible to measure TPOAb and TgAb in all samples with the AutoDELFIA. There is no systematic variation in autoantibodies during the menstrual cycle. The biological coefficient of variation for TPOAb and TgAb was 11.3% and 8.5%, respectively...

  3. Nonorgan specific autoantibodies and heart damage.

    Science.gov (United States)

    Tincani, A; Biasini-Rebaioli, C; Cattaneo, R; Riboldi, P

    2005-01-01

    Heart damage, mediated by different autoantibodies can involve several anatomical heart structures: valves, arteries, conduction tissue. Verrucous endocarditis is frequently reported in patients with antiphospholipid syndrome (APS) with or without systemic lupus erythematosus (SLE), particularly if they suffer from central nervous system involvement. Antiphospholipid antibodies (aPL) were shown deposited at subendothelial level of the affected valves. According to several in vitro and in vivo experimental models, aPL, anti-oxidized LDL (oxLDL), anti-heat shock protein 65 (HSP65) and anti-endothelial cells antibodies (AECA) seem to be involved in the pathogenesis of the atherosclerosis phenomena described in systemic autoimmune disease and vasculitis. However, the observation of the association of the same antibodies with clinical and subclinical atherosclerosis in patients is still controversial. The children of anti-Ro/SSA positive mothers can be affected by the congenital heart block. Anti Ro/SS-A antibodies play a major pathogenic role in affecting the heart conduction tissue in this rare condition.

  4. Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy.

    Science.gov (United States)

    Huang, Zhi Qiang; Raska, Milan; Stewart, Tyler J; Reily, Colin; King, R Glenn; Crossman, David K; Crowley, Michael R; Hargett, Audra; Zhang, Zhixin; Suzuki, Hitoshi; Hall, Stacy; Wyatt, Robert J; Julian, Bruce A; Renfrow, Matthew B; Gharavi, Ali G; Novak, Jan

    2016-11-01

    Autoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactose-deficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y 1 CS 3 , in the complementarity-determining region 3 of the heavy chain variable region compared with a Y 1 CA 3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S 3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls from whom we had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y 1 C(A/V) 3 amino-acid sequence. Thus, the A/V>S substitution in the complementarity-determining region 3 of anti-galactose-deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S 3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent β-sheet and stem structure, important features for effective binding to galactose-deficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy. Copyright © 2016 by the American Society of Nephrology.

  5. Brief Communication: Maternal Plasma Autoantibodies Screening in Fetal Down Syndrome

    Directory of Open Access Journals (Sweden)

    Karol Charkiewicz

    2016-01-01

    Full Text Available Imbalance in the metabolites levels which can potentially be related to certain fetal chromosomal abnormalities can stimulate mother’s immune response to produce autoantibodies directed against proteins. The aim of the study was to determine the concentration of 9000 autoantibodies in maternal plasma to detect fetal Down syndrome. Method. We performed 190 amniocenteses and found 10 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation. For the purpose of our control we chose 11 women without confirmed chromosomal aberration. To assess the expression of autoantibodies in the blood plasma, we used a protein microarray, which allows for simultaneous determination of 9000 proteins per sample. Results. We revealed 213 statistically significant autoantibodies, whose expression decreased or increased in the study group with fetal Down syndrome. The second step was to create a classifier of Down syndrome pregnancy, which includes 14 antibodies. The predictive value of the classifier (specificity and sensitivity is 100%, classification errors, 0%, cross-validation errors, 0%. Conclusion. Our findings suggest that the autoantibodies may play a role in the pathophysiology of Down syndrome pregnancy. Defining their potential as biochemical markers of Down syndrome pregnancy requires further investigation on larger group of patients.

  6. Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals

    DEFF Research Database (Denmark)

    von Stemann, Jakob Hjorth; Rigas, Andreas Stribolt; Thørner, Lise Wegner

    2017-01-01

    Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero...

  7. Estimating autoantibody signatures to detect autoimmune disease patient subsets.

    Science.gov (United States)

    Wu, Zhenke; Casciola-Rosen, Livia; Shah, Ami A; Rosen, Antony; Zeger, Scott L

    2017-11-13

    Autoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are onerous and expensive to validate. We set out to establish a method to greatly simplify autoantibody discovery, using a pre-filtering step to define subgroups with similar specificities based on migration of radiolabeled, immunoprecipitated proteins on sodium dodecyl sulfate (SDS) gels and autoradiography [Gel Electrophoresis and band detection on Autoradiograms (GEA)]. Human recognition of patterns is not optimal when the patterns are complex or scattered across many samples. Multiple sources of errors-including irrelevant intensity differences and warping of gels-have challenged automation of pattern discovery from autoradiograms.In this article, we address these limitations using a Bayesian hierarchical model with shrinkage priors for pattern alignment and spatial dewarping. The Bayesian model combines information from multiple gel sets and corrects spatial warping for coherent estimation of autoantibody signatures defined by presence or absence of a grid of landmark proteins. We show the pre-processing creates more clearly separated clusters and improves the accuracy of autoantibody subset detection via hierarchical clustering. Finally, we demonstrate the utility of the proposed methods with GEA data from scleroderma patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Fly Photoreceptors Encode Phase Congruency.

    Directory of Open Access Journals (Sweden)

    Uwe Friederich

    Full Text Available More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli.

  9. Fly Photoreceptors Encode Phase Congruency.

    Science.gov (United States)

    Friederich, Uwe; Billings, Stephen A; Hardie, Roger C; Juusola, Mikko; Coca, Daniel

    2016-01-01

    More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli.

  10. Performance characteristics of 5 automated thyroglobulin autoantibody and thyroid peroxidase autoantibody assays.

    Science.gov (United States)

    La'ulu, Sonia L; Slev, Patricia R; Roberts, William L

    2007-02-01

    Measurement of thyroid peroxidase autoantibodies (TPOAb) is useful in diagnosing patients with autoimmune thyroid disease. Measurement of thyroglobulin autoantibodies (TgAb) is used to detect potential interferences with thyroglobulin immunoassays and in limited situations for the diagnosis of autoimmune thyroid disease. The limit of detection, imprecision, reference interval, method comparison and diagnostic concordance for the ADVIA Centaur, ARCHITECT i2000, AxSYM, Immulite 2000, Modular E170 (TPOAb only), and UniCel DxI 800 (TgAb only) methods were evaluated. The Advantage was used as the comparison method. Total imprecision ranged from 2.6% to 14.9% for TgAb and 2.1% to 15.8% for TPOAb. Passing-Bablok slopes ranged from 0.51 to 10.4 (TgAb) and 1.05 to 7.12 (TPOAb) with correlation coefficients of 0.48 to 0.82 (TgAb) and 0.66 to 0.78 (TPOAb). Assay cutoffs were adjusted using a common set of reference interval samples. Concordance with the Advantage assay using the new cutoffs was found to be improved and ranged from 68.5% to 84.7% (TgAb) and 77.5% to 84.7% (TPOAb). Although all assays generally performed well, assay concordance for a negative or positive result ranged from 54.2 to 84.7%. Quantitative agreement between methods was generally poor and methods could not be used interchangeably. Additional standardization efforts are required to improve inter-method agreement.

  11. Analysing and Comparing Encodability Criteria

    Directory of Open Access Journals (Sweden)

    Kirstin Peters

    2015-08-01

    Full Text Available Encodings or the proof of their absence are the main way to compare process calculi. To analyse the quality of encodings and to rule out trivial or meaningless encodings, they are augmented with quality criteria. There exists a bunch of different criteria and different variants of criteria in order to reason in different settings. This leads to incomparable results. Moreover it is not always clear whether the criteria used to obtain a result in a particular setting do indeed fit to this setting. We show how to formally reason about and compare encodability criteria by mapping them on requirements on a relation between source and target terms that is induced by the encoding function. In particular we analyse the common criteria full abstraction, operational correspondence, divergence reflection, success sensitiveness, and respect of barbs; e.g. we analyse the exact nature of the simulation relation (coupled simulation versus bisimulation that is induced by different variants of operational correspondence. This way we reduce the problem of analysing or comparing encodability criteria to the better understood problem of comparing relations on processes.

  12. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Satoko Arai

    2013-04-01

    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  13. Autoantibody-mediated cardiac arrhythmias: mechanisms and clinical implications.

    Science.gov (United States)

    Lazzerini, Pietro Enea; Capecchi, Pier Leopoldo; Guideri, Francesca; Acampa, Maurizio; Selvi, Enrico; Bisogno, Stefania; Galeazzi, Mauro; Laghi-Pasini, Franco

    2008-01-01

    Cardiac arrhythmias, including conduction defects and tach- yarrhythmias, represent an important source of morbidity and mortality in industrialized countries. Among the different pathophysiological mechanisms involved in the arrhythmogenesis, an inappropriate activation of the immune system represents a field of recent increasing interest. In fact, a large amount of studies suggest that specific autoantibody may be significantly involved in the pathogenesis of cardiac arrhythmias not only in the course of systemic autoimmune disease, but also in a number of rhythm disorders currently classified as "idiopathic." Although the strongest evidence concerns the relationship between anti-Ro/SSA antibodies and the development of congenital heart block in foetus and newborn, other specific autoantibodies demonstrated the aptitude to affect directly the myocardial tissue, thus producing interference in its bioelectric activity thereby leading to rhythm disorders, also life-threatening. The identification of an immunological autoantibody-mediated mechanism opens new perspectives in the treatment and prevention of cardiac arrhythmias in such patients, including the use of immunosuppressive agents and/or the removal of autoantibodies by immuno-adsorption technique.

  14. Measurement of antiacetylcholine receptor auto-antibodies in ...

    African Journals Online (AJOL)

    Two different acetylcholine receptor (AChR) preparations derived from amputated human muscle (AChRAMP) and from the human rhabdomyosarcoma cell line TE671 (AChRTE67,) were compared in radio-immunoprecipitation assays for the detection of AChR auto-antibodies in serum specimens from 20 patients with ...

  15. Measurement of anti- acetylcholine receptor auto-antibodies in ...

    African Journals Online (AJOL)

    Two different acetylcholine receptor (AChR) preparations derived from amputated human muscle (AChRAMP) and from the human rhabdomyosarcoma cell line TE671 (AChRTE67,) were compared in radio-immunoprecipitation assays for the detection of AChR auto-antibodies in serum specimens from 20 patients with ...

  16. Clinical utility of autoantibodies and biologic markers in rheumatoid ...

    African Journals Online (AJOL)

    Objective: To review the current and emerging auto-antibodies and biologic markers in rheumatoid arthritis. Data source: Published original research work and reviews were searched in English related to pathophysiology, diagnosis and auto antibodies in rheumatoid arthritis. Study design: Only articles that emphasis on ...

  17. Diagnostic Utility of Auto-Antibodies in Inflammatory Muscle Diseases.

    Science.gov (United States)

    Allenbach, Y; Benveniste, O

    2015-01-01

    To date, there are four main groups of idiopathic inflammatory myopathies (IIM): polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis; based on clinical presentation and muscle pathology. Nevertheless, important phenotypical differences (either muscular and/or extra-muscular manifestations) within a group persist. In recent years, the titration of different myositis-specific (or associated) auto-antibodies as a diagnostic tool has increased. This is an important step forward since it may facilitate, at a viable cost, the differential diagnosis between IIM and other myopathies. We have now routine access to assays for the detection of different antibodies. For example, IMNM are related to the presence of anti-SRP or anti-HMGCR. PM is associated with anti-synthetase antibodies (anti-Jo-1, PL-7, PL-12, OJ, and EJ) and DM with anti-Mi-2, anti-SAE, anti-TIF-1-γ and anti-NXP2 (both associated with cancer) or anti-MDA5 antibodies (associated with interstitial lung disease). Today, over 30 myositis specific and associated antibodies have been characterised, and all groups of myositis may present one of those auto-antibodies. Most of them allow identification of homogenous patient groups, more precisely than the classical international classifications of myositis. This implies that classification criteria could be modified accordingly, since these auto-antibodies delineate groups of patients suffering from myositis with consistent clinical phenotype (muscular and extra-muscular manifestations), common prognostic (cancer association, presence of interstitial lung disease, mortality and risk of relapse) and treatment responses. Nevertheless, since numerous auto-antibodies have been recently characterised, the exact prevalence of myositis specific antibodies remains to be documented, and research of new auto-antibodies in the remaining seronegative group is still needed.

  18. MicroRNAs Encoded by Bovine Leukemia Virus (BLV Are Associated with Reduced Expression of B Cell Transcriptional Regulators in Dairy Cattle Naturally Infected with BLV

    Directory of Open Access Journals (Sweden)

    Meredith C. Frie

    2018-01-01

    Full Text Available Bovine leukemia virus (BLV is estimated to infect over 83% of dairy herds and over 40% of all dairy cows in the United States. While, BLV only causes leukemia in a small proportion of animals, research indicates that BLV+ cattle exhibit reduced milk production and longevity that is distinct from lymphoma development. It is hypothesized that BLV negatively affects production by interfering with cattle immunity and increasing the risk of secondary infections. In particular, BLV+ cows demonstrate reduced circulating levels of both antigen-specific and total IgM. This study investigated possible mechanisms by which BLV could interfere with the production of IgM in naturally infected cattle. Specifically, total plasma IgM and the expression of genes IGJ, BLIMP1, BCL6, and PAX5 in circulating IgM+ B cells were measured in 15 naturally infected BLV+ and 15 BLV− cows. In addition, BLV proviral load (PVL (a relative measurement of BLV provirus integrated into host DNA and the relative expression of BLV TAX and 5 BLV microRNAs (miRNAs were characterized and correlated to the expression of selected endogenous genes. BLV+ cows exhibited lower total plasma IgM and lower expression of IGJ, BLIMP1, and BCL6. While, BLV TAX and BLV miRNAs failed to correlate with IGJ expression, both BLV TAX and BLV miRNAs exhibited negative associations with BLIMP1 and BCL6 gene expression. The results suggest a possible transcriptional pathway by which BLV interferes with IgM production in naturally infected cattle.

  19. Thyroid autoantibodies and differentiated thyroid cancer: revue of 662 cases

    International Nuclear Information System (INIS)

    Izembart, M.; Dagousset, F.; Chevalier, A.; Hassid, V.; Leger, A.; Barritault, L.; Clerc, J.

    1999-01-01

    The incidence of thyroid autoantibodies is clearly increased in patients with differentiated thyroid cancer. The aim of this study was to re-evaluate frequency and evolution of anti-thyroglobulin and anti-microsomal (anti-peroxidase) autoantibodies in 662 patients with thyroid carcinoma treated with 131 radioiodine. Ours results obtained with 'classical' methods confirmed others earlier reports. When using more sensitive methods to detect thyroglobulin antibodies we obtained an increase in positive results and a more frequent association with anti-microsomal antibodies. Antibodies became undetectable with a variable period, ranging from a few months to 13 years in one case. If we suppose that the disappearance of antibodies is linked to the thyroid tissue disappearance, thyroid cancer follow up ought to include anti-thyroglobulin and anti-peroxidase antibodies, both directed against thyroid antigens. A decrease of both antibodies seems to indicate a favorable prognostic factor whereas an increase may suggest relapse. (author)

  20. Pathogenicity of autoantibodies in anti-p200 pemphigoid.

    Directory of Open Access Journals (Sweden)

    Katerina Vafia

    Full Text Available Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7 induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609. Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid.

  1. Thyroid autoantibodies in autoimmune diseases Anticuerpos antitiroideos en enfermedades autoinmunes

    OpenAIRE

    Regina M. Innocencio; João H. Romaldini; Laura S. Ward

    2004-01-01

    Abnormalities in the thyroid function and thyroid autoantibodies have been frequently described in patients with autoimmune diseases but seldom in antiphospholipid syndrome patients. In order to determine the prevalence of thyroid function and autoimmune abnormalities, we compared serum thyrotropin (TSH, serum free thyroxine (T4) levels, thyroid antithyroglobulin (TgAb) and antithyroperoxidase (TPOAb) levels of 25 patients with systemic sclerosis, 25 patients with rheumatoid arthritis and 13 ...

  2. Female Infertility and Serum Auto-antibodies: a Systematic Review.

    Science.gov (United States)

    Deroux, Alban; Dumestre-Perard, Chantal; Dunand-Faure, Camille; Bouillet, Laurence; Hoffmann, Pascale

    2017-08-01

    On average, 10 % of infertile couples have unexplained infertility. Auto-immune disease (systemic lupus erythematosus, anti-phospholipid syndrome) accounts for a part of these cases. In the last 20 years, aspecific auto-immunity, defined as positivity of auto-antibodies in blood sample without clinical or biological criteria for defined diseases, has been evoked in a subpopulation of infertile women. A systematic review was performed (PUBMED) using the MESH search terms "infertility" and "auto-immunity" or "reproductive technique" or "assisted reproduction" or "in vitro fertilization" and "auto-immunity." We retained clinical and physiopathological studies that were applicable to the clinician in assuming joint management of both infertility associated with serum auto-antibodies in women. Thyroid auto-immunity which affects thyroid function could be a cause of infertility; even in euthyroidia, the presence of anti-thyroperoxydase antibodies and/or thyroglobulin are related to infertility. The presence of anti-phospholipid (APL) and/or anti-nuclear (ANA) antibodies seems to be more frequent in the population of infertile women; serum auto-antibodies are associated with early ovarian failure, itself responsible for fertility disorders. However, there exist few publications on this topic. The methods of dosage, as well as the clinical criteria of unexplained infertility deserve to be standardized to allow a precise response to the question of the role of serum auto-antibodies in these women. The direct pathogenesis of this auto-immunity is unknown, but therapeutic immunomodulators, prescribed on a case-by-case basis, could favor pregnancy even in cases of unexplained primary or secondary infertility.

  3. Clinical Significance of Autoantibodies in Some Thyroid Disorders

    International Nuclear Information System (INIS)

    Choi, Sung Kyu; Han, Sang Ho; Kim, Young Ju; Song, Jun Ho; Lee, Man Ho; Chung, Eul Sun; Lee, Sang Jong

    1984-01-01

    Clinical measurement of thyroid autoantibodies in sera of some thyroid disorders have been widely applied since about twenty years ago. We investigated the incidence and titers of both antimicrosomal and antithyroglobulin antibodies in forty eight cases with controls and one hundred and thirty three patients with some form of thyroid disorders. The results were as follows; 1) In controls, antimicrosomal antibodies were positive in 2% but antithyroglobulin antibodies were all negative. 2) In a series of one hundred and thirty three patients with thyroid disease, antimicrosomal antibodies were positive in 44% but antithyroglobulin antibodies were positive in only 15%. 3) The rate disclosing the positive results of antimicrosomal antibodies were 71% in Hashimoto disease, 60% in Graves' disease, and 38% in primary hypothyroidism, respectively. On the other hand, the positive results of antithyroglobulin antibodies showed 21% in Graves' disease, 19% in primary hypothyroidism, and 18% in Hashimoto, disease, respectively. Though there were relatively high rate of both antimicrosomal and antithyroglobulin antibodies in patients with nodular goiter, they were only seven cases in our series. 4) The rate with the extremely high titers of antimicrosomal and antithyroglobulin antibodies (>1 : 160 2 ) was 83% and 67% in Hashimoto's disease, 50% and 67% in primary hypothyroidism, and 41% and 18% in Graves' disease. Accordingly, the thyroid autoantibodies, were commonly found higher positive rate in patients with Hashimoto disease, primary hypothyroidism, and Graves' disease. Among these disorders, the extremely high positive rate of the thyroid autoantibodies was found in patients with Hashimoto's disease.

  4. Coeliac disease autoantibodies mediate significant inhibition of tissue transglutaminase.

    LENUS (Irish Health Repository)

    Byrne, Greg

    2012-02-01

    The detection of antibodies directed against tissue transglutaminase (tTG) in serum is a sensitive and specific test for suspected coeliac disease. tTG is a ubiquitous, multifunctional enzyme that has been implicated in many important physiological processes as well as the site-specific deamidation of glutamine residues in gluten-derived peptides. This modification of gluten peptides facilitates their binding to HLA-DQ2, which results in amplification of the T-cell response to gluten. The purpose of this study was to investigate the possibility that patient IgA autoantibodies directed against tTG interfere with the crosslinking activity of the enzyme. IgA autoantibodies against tTG were isolated\\/depleted from patient serum and tested for their capacity to interfere with tTG activity in vitro using a sensitive fluorescence-based activity assay. We have demonstrated that autoantibodies cause significant inhibition of tTG-mediated crosslinking at equimolar and 2:1 ratios of antibody to enzyme.

  5. The Hypothalamic–Pituitary Axis and Autoantibody Related Disorders

    Directory of Open Access Journals (Sweden)

    Cristina Cocco

    2017-11-01

    Full Text Available This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs and/or hypothalamus (AHAs. Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities. APAs to growth hormone (GH cells have been associated with GH deficiency while those against the adrenocorticotropic cells have distinguished central Cushing’s disease patients at risk of incomplete cure after surgical adenoma removal. AHAs to vasopressin cells have identified patients at risk of developing diabetes insipidus. APAs have been also found together with AHAs in patients affected by idiopathic hypopituitarism, but both were also present in different kinds of patients without abnormalities of the hypothalamic–pituitary axis. Despite some data being promising, the clinical use of pituitary and hypothalamus autoantibodies is still limited by the low diagnostic sensitivity, irreproducibility of the results, and the absence of autoantigen/s able to discriminate the autoimmune reaction involving the pituitary or the hypothalamus from the other autoimmune states.

  6. Extrahepatic Manifestations and Autoantibodies in Patients with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2012-01-01

    Full Text Available Patients with chronic hepatitis C virus (HCV infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren’s syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.

  7. Estimating AutoAntibody Signatures to Detect Autoimmune Disease Patient Subsets

    OpenAIRE

    Wu, Zhenke; Casciola-Rosen, Livia; Shah, Ami A.; Rosen, Antony; Zeger, Scott

    2017-01-01

    Autoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are one...

  8. Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Lan Li

    2017-01-01

    Full Text Available Esophageal squamous cell carcinoma (ESCC, one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA. Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P<0.0001. Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P<0.0001. Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.

  9. To look for a needle in a haystack: the search for autoantibodies in multiple sclerosis.

    Science.gov (United States)

    Schirmer, Lucas; Srivastava, Rajneesh; Hemmer, Bernhard

    2014-03-01

    The search for autoantibodies in multiple sclerosis (MS) has been challenging for the last 3 decades. With the development of new proteomic methods and advances in expression and assay technologies, progress in the identification of MS autoantibodies has been made. A number of MS-specific autoantibodies have been proposed, most of them targeting proteins expressed in oligodendrocytes and along the myelin sheath. In this review, we summarize the status of antibody research in MS and then discuss recent developments and future strategies in defining and characterizing the potential antigenic targets of autoantibodies in MS.

  10. Association between anti-thyroid peroxidase and anti-cytokeratin 18 autoantibodies and bronchial asthma in women

    Directory of Open Access Journals (Sweden)

    Hala A. Mohammad

    2016-01-01

    Conclusion: Positive anti-TPO autoantibodies and anti-CK18 autoantibodies in asthmatic patients and their higher level in the non-allergic asthma group may strengthen the presence of a hidden autoimmune phenomenon in non-allergic asthma.

  11. natural

    Directory of Open Access Journals (Sweden)

    Elías Gómez Macías

    2006-01-01

    Full Text Available Partiendo de óxido de magnesio comercial se preparó una suspensión acuosa, la cual se secó y calcinó para conferirle estabilidad térmica. El material, tanto fresco como usado, se caracterizó mediante DRX, área superficial BET y SEM-EPMA. El catalizador mostró una matriz de MgO tipo periclasa con CaO en la superficie. Las pruebas de actividad catalítica se efectuaron en lecho fijo empacado con partículas obtenidas mediante prensado, trituración y clasificación del material. El flujo de reactivos consistió en mezclas gas natural-aire por debajo del límite inferior de inflamabilidad. Para diferentes flujos y temperaturas de entrada de la mezcla reactiva, se midieron las concentraciones de CH4, CO2 y CO en los gases de combustión con un analizador de gases tipo infrarrojo no dispersivo (NDIR. Para alcanzar conversión total de metano se requirió aumentar la temperatura de entrada al lecho a medida que se incrementó el flujo de gases reaccionantes. Los resultados obtenidos permiten desarrollar un sistema de combustión catalítica de bajo costo con un material térmicamente estable, que promueva la alta eficiencia en la combustión de gas natural y elimine los problemas de estabilidad, seguridad y de impacto ambiental negativo inherentes a los procesos de combustión térmica convencional.

  12. Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis.

    Science.gov (United States)

    Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan

    2017-09-01

    Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

    Science.gov (United States)

    Middleton, Catrin H.; Irving, William; Robertson, John F. R.; Murray, Andrea; Parsy-Kowalska, Celine B.; Macdonald, Isabel K.; McElveen, Jane; Allen, Jared; Healey, Graham F.; Thomson, Brian J.; Ryder, Stephen J.; Holdenrieder, Stefan; Chapman, Caroline J.

    2014-01-01

    Background Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC. Methods Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. Results Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. Conclusions This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung). PMID:25093332

  14. Serum autoantibody measurement for the detection of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Catrin H Middleton

    Full Text Available BACKGROUND: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs in the serum of patients with HCC. METHODS: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. RESULTS: Varying autoantibody specificities (97-100% and sensitivities (0-10% were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. CONCLUSIONS: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography and to similar tests in other cancers (EarlyCDT-Lung.

  15. Identification of novel autoantibodies for detection of malignant mesothelioma.

    Directory of Open Access Journals (Sweden)

    Xufei Zhang

    Full Text Available The malignant mesothelioma (MM survival rate has been hampered by the lack of efficient and accurate early detection methods. The immune system may detect the early changes of tumor progression by responding with tumor-associated autoantibody production. Hence, in this study, we translated the humoral immune response to cancer proteins into a potential blood test for MM.A T7 phage MM cDNA library was constructed using MM tumor tissues and biopanned for tumor-associated antigens (TAAs using pooled MM patient and normal serum samples. About 1008 individual phage TAA clones from the biopanned library were subjected to protein microarray construction and tested with 53 MM and 52 control serum samples as a training group. Nine candidate autoantibody markers were selected from the training group using Tclass system and logistic regression statistical analysis, which achieved 94.3% sensitivity and 90.4% specificity with an AUC value of 0.89 in receiver operating characteristic analysis. The classifier was further evaluated with 50 patient and 50 normal serum samples as an independent blind validation, and the sensitivity of 86.0% and the specificity of 86.0% were obtained with an AUC of 0.82. Sequencing and BLASTN analysis of the classifier revealed that five of these nine candidate markers were found to have strong homology to cancer related proteins (PDIA6, MEG3, SDCCAG3, IGHG3, IGHG1.Our results indicated that using a panel of 9 autoantibody markers presented a promising accuracy for MM detection. Although the results need further validation in high-risk groups, they provided the potentials in developing a serum-based assay for MM diagnosis.

  16. Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

    NARCIS (Netherlands)

    Schaper, F.; de Leeuw, K.; Horst, G.; Maas, F.; Bootsma, H.; Heeringa, P.; Limburg, P. C.; Westra, J.

    Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for

  17. Autoantibodies against interleukin 1alpha in rheumatoid arthritis: association with long term radiographic outcome

    DEFF Research Database (Denmark)

    Graudal, N A; Svenson, M; Tarp, Ulrik

    2002-01-01

    To investigate the possible association of interleukin 1alpha autoantibodies (IL1alpha aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA).......To investigate the possible association of interleukin 1alpha autoantibodies (IL1alpha aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA)....

  18. Autoantibodies to myeloperoxidase aggravate mild anti-glomerular-basement-membrane-mediated glomerular injury in the rat

    NARCIS (Netherlands)

    Heeringa, P.; Brouwer, E.; Klok, P. A.; Huitema, M. G.; van den Born, J.; Weening, J. J.; Kallenberg, C. G.

    1996-01-01

    Autoantibodies to myeloperoxidase (MPO) are present in sera from patients with various forms of vasculitis-associated glomerulonephritis. Evidence for a pathogenic role of anti-MPO antibodies has been provided mainly by in vitro studies. We studied the pathogenic role of autoantibodies to MPO in a

  19. Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

    NARCIS (Netherlands)

    Schaper, F.; Leeuw, K. de; Horst, G. ter; Maas, F.; Bootsma, H.; Heeringa, P.; Limburg, P.C.; Westra, J.

    2017-01-01

    Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for

  20. Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen

    NARCIS (Netherlands)

    Zillikens, D; Ishiko, A; Jonkman, MF; Chimanovitch, [No Value; Shimizu, H; Hashimoto, T; Brocker, EB

    2000-01-01

    We report the case of a patient with a widespread bullous skin disease and linear deposits of IgG and C3 at the dermal-epidermal junction using direct immunofluorescence microscopy. Indirect immunofluorescence analysis demonstrated circulating IgG autoantibodies that stained, like autoantibodies to

  1. GAD65 autoantibodies in women with gestational or insulin dependent diabetes mellitus diagnosed during pregnancy

    DEFF Research Database (Denmark)

    Petersen, J S; Dyrberg, Torben Bech; Damm, P

    1996-01-01

    We have studied the presence of GAD65 autoantibodies in women with insulin-dependent diabetes mellitus (IDDM) (n = 28) or gestational diabetes (GDM) (n = 139) diagnosed during pregnancy and investigated the temporal relationship between these autoantibodies and the subsequent recurrence...

  2. 14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

    NARCIS (Netherlands)

    Maksymowych, Walter P.; Boire, Gilles; van Schaardenburg, Dirkjan; Wichuk, Stephanie; Turk, Samina; Boers, Maarten; Siminovitch, Katherine A.; Bykerk, Vivian; Keystone, Ed; Tak, Paul Peter; van Kuijk, Arno W.; Landewé, Robert; van der Heijde, Desiree; Murphy, Mairead; Marotta, Anthony

    2015-01-01

    To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA). 14-3-3η autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with

  3. Autoantibodies persist in relatives to systemic lupus erythematosus patients during 12 years follow-up

    DEFF Research Database (Denmark)

    Langkilde, Henrik; Voss, A; Heegaard, N

    2017-01-01

    BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with presence of autoantibodies and characteristic multi-organ involvement. Relatives of SLE patients have an increased risk of autoantibody production and autoimmune diseases. METHODS: In 2001, 226 first degree relatives (FDRs...

  4. Characterization of genetic predisposition and autoantibody profile in atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Gurjar, Bahadur Singh; Sriharsha, T Manikanta; Bhasym, Angika; Prabhu, Savit; Puraswani, Mamta; Khandelwal, Priyanka; Saini, Himanshi; Saini, Savita; Verma, Anita Kamra; Chatterjee, Priyadarshini; Gucchait, Prasenjit; Bal, Vineeta; George, Anna; Rath, Satyajit; Sahu, Arvind; Sharma, Amita; Hari, Pankaj; Sinha, Aditi; Bagga, Arvind

    2018-02-27

    We previously reported that Indian pediatric patients of atypical hemolytic-uremic syndrome (aHUS) showed high frequencies of anti-complement factor H (FH) autoantibodies that are correlated with homozygous deletion of the genes for FH-related proteins 1 and 3 (FHR1 and FHR3) (FHR1/3-/-). We now report that Indian pediatric aHUS patients without anti-FH autoantibodies also showed modestly higher frequencies of the FHR1/3-/- genotype. Further, when we characterized epitope specificities and binding avidities of anti-FH autoantibodies in aHUS patients, most anti-FH autoantibodies were directed towards the FH cell-surface anchoring polyanionic binding site-containing C-terminal short conservative regions (SCRs) 17-20 with higher binding avidities than for native FH. FH SCR17-20-binding anti-FH autoantibodies also bound the other cell-surface anchoring polyanionic binding site-containing region FH SCR5-8, at lower binding avidities. Anti-FH autoantibody avidities correlated with antibody titres. These anti-FH autoantibody characteristics did not differ between aHUS patients with or without the FHR1/3-/- genotype. Our data suggest a complex matrix of interactions between FHR1-FHR3 deletion, immunomodulation and anti-FH autoantibodies in the etiopathogenesis of aHUS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Autoantibodies to complement components in C3 glomerulopathy and atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Józsi, Mihály; Reuter, Stefanie; Nozal, Pilar; López-Trascasa, Margarita; Sánchez-Corral, Pilar; Prohászka, Zoltán; Uzonyi, Barbara

    2014-08-01

    The alternative pathway of complement is implicated in the pathogenesis of several renal diseases, such as atypical hemolytic uremic syndrome, dense deposit disease and other forms of C3 glomerulopathy. The underlying complement defects include genetic and/or acquired factors, the latter in the form of autoantibodies. Because the autoimmune forms require a specific treatment, in part different from that of the genetic forms, it is important to detect the autoantibodies as soon as possible and understand their characteristics. In this overview, we summarize the types of anti-complement autoantibodies detected in such diseases, i.e. autoantibodies to factor H, factor I, C3b, factor B and those against the C3 convertases (C3 nephritic factor and C4 nephritic factor). We draw attention to newly described autoantibodies and their characteristics, and highlight similarities and differences in the autoimmune forms of these diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Red cell autoantibodies characterized by competitive inhibition of iodine 125 Rh alloantibody binding and by immunoprecipitation of membrane proteins

    International Nuclear Information System (INIS)

    Pierce, S.W.; Victoria, E.J.; Masouredis, S.P.

    1990-01-01

    The relationship between determinants recognized by warm-type immunoglobulin G red cell autoantibodies and the Rh antigens was characterized by autoantibody competitive inhibition of iodine 125 Rh alloantibody binding and autoantibody immunoprecipitation of iodine 125 red blood cell membrane proteins. The majority of blood donor autoantibody recognized epitopes that are closely related to Rh antigens as determined by competitive inhibition studies. Eighteen of 20 (90%) autoantibodies inhibited anti-Rh(c) binding, 15 inhibited anti-Rh(E), 5 inhibited anti-Rh(D), and only 2 failed to inhibit any of the three Rh alloantibodies tested. Autoantibodies that inhibited anti-Rh(D) also inhibited anti-Rh(c) and anti-Rh(E) and all those that inhibited anti-Rh(E) also inhibited anti-Rh(c). Autoantibodies that inhibited all three Rh alloantibodies immunoprecipitated 30 kd membrane polypeptides, as did two of the three autoantibodies that inhibited only anti-Rh(c) and anti-Rh(E). One autoantibody in this group and two autoantibodies that inhibited only anti-Rh(c), as well as an autoantibody that did not inhibit any of the Rh alloantibodies, immunoprecipitated only a single membrane polypeptide identified as band 3. The majority of normal donor red blood cell autoantibodies inhibited the binding of Rh alloantibodies, which indicates that they either bound to the Rh polypeptides or to epitopes on band 3 that were closely associated with the Rh complex

  7. A viral vaccine encoding PSA induces antigen spreading to a common set of self proteins in prostate cancer patients

    Science.gov (United States)

    Nesslinger, Nancy J.; Ng, Alvin; Tsang, Kwong-Yok; Ferrara, Theresa; Schlom, Jeff; Gulley, James L.; Nelson, Brad H.

    2010-01-01

    Purpose We previously reported a randomized phase II clinical trial combining a poxvirus-based vaccine encoding PSA with radiotherapy in patients with localized prostate cancer. Here we investigate whether vaccination against PSA induced immune responses to additional tumor-associated antigens and how this influenced clinical outcome. Experimental Design Pre- and post-treatment serum samples from patients treated with vaccine + external beam radiation therapy (EBRT) versus EBRT alone were evaluated by Western blot and serological screening of a prostate cancer cDNA expression library (SEREX) to assess the development of treatment-associated autoantibody responses. Results Western blotting revealed treatment-associated autoantibody responses in 15/33 (45.5%) patients treated with vaccine + EBRT versus 1/8 (12.5%) treated with EBRT alone. SEREX screening identified 18 antigens, which were assembled on an antigen array with 16 previously identified antigens. Antigen array screening revealed that seven of 33 patients (21.2%) treated with vaccine + EBRT demonstrated a vaccine-associated autoantibody response to four ubiquitously expressed self antigens: DIRC2, NDUFS1, MRFAP1 and MATN2. These responses were not seen in patients treated with EBRT alone, or other control groups. Patients with autoantibody responses to this panel of antigens had a trend towards decreased biochemical-free survival. Conclusions Vaccine + EBRT induced antigen spreading in a large proportion of patients. A subset of patients developed autoantibodies to a panel of four self antigens and showed a trend toward inferior outcomes. Thus, cancer vaccines directed against tumor-specific antigens can trigger autoantibody responses to self proteins, which may influence the efficacy of vaccination. PMID:20562209

  8. Use of Autoantibodies to Detect the Onset of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jérôme Lacombe

    2014-01-01

    Full Text Available The widespread use of screening mammography has resulted in increased detection of early-stage breast disease, particularly for in situ carcinoma and early-stage breast cancer. However, the majority of women with abnormalities noted on screening mammograms are not diagnosed with cancer because of several factors, including radiologist assessment, patient age, breast density, malpractice concerns, and quality control procedures. Although magnetic resonance imaging is a highly sensitive detection tool that has become standard for women at very high risk of developing breast cancer, it lacks sufficient specificity and costeffectiveness for use as a general screening tool. Therefore, there is an important need to improve screening and diagnosis of early-invasive and noninvasive tumors, that is, in situ carcinoma. The great potential for molecular tools to improve breast cancer outcomes based on early diagnosis has driven the search for diagnostic biomarkers. Identification of tumor-specific markers capable of eliciting an immune response in the early stages of tumor development seems to provide an effective approach for early diagnosis. The aim of this review is to describe several autoantibodies identified during breast cancer diagnosis. We will focus on these molecules highlighted in the past two years and discuss the potential future use of autoantibodies as biomarkers of early-stage breast cancer.

  9. Obstetric and vascular APS: same autoantibodies but different diseases?

    Science.gov (United States)

    Meroni, P L; Raschi, E; Grossi, C; Pregnolato, F; Trespidi, L; Acaia, B; Borghi, M O

    2012-06-01

    Beta2 glycoprotein I (β2GPI)-dependent antiphospholipid antibodies (aPLs) are the main pathogenic autoantibody population and at the same time the laboratory diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are responsible for both the vascular and the obstetric manifestations of the syndrome but the pathogenic mechanisms behind these manifestations are not the same. For example, thrombotic events do not appear to play a major role in APS miscarriages and a direct reactivity of β2GPI-dependent aPLs on decidual and trophoblast cells was reported. A local expression of β2GPI on these tissues was reported both in physiological conditions and in APS women, thus explaining the local tropism of the autoantibodies. The two hit hypothesis was suggested to explain why the vascular manifestations of APS may occur only occasionally in spite of the persistent presence of aPLs. This is not apparently the case for the obstetric variant of the syndrome, making the difference even more striking. A different pathogenesis may also provide the rationale for the well-known fact that the vascular and the obstetric manifestations may occur independently although in a minority of cases.

  10. Immunospecific red cell binding of iodine 125-labeled immunoglobulin G erythrocyte autoantibodies

    International Nuclear Information System (INIS)

    Masouredis, S.P.; Branks, M.J.; Garratty, G.; Victoria, E.J.

    1987-01-01

    The primary interaction of autoantibodies with red cells has been studied by using labeled autoantibodies. Immunoglobulin G red cell autoantibodies obtained from IgG antiglobulin-positive normal blood donors were labeled with radioactive iodine and compared with alloanti-D with respect to their properties and binding behavior. Iodine 125 -labeled IgG autoantibody migrated as a single homogeneous peak with the same relative mobility as human IgG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric focusing pattern of labeled autoantibodies varied from donor to donor but was similar to that of alloanti-D, consisting of multiple IgG populations with isoelectric points in the neutral to alkaline range. 125 I-autoantibody bound to all human red cells of common Rh phenotypes. Evidence for immunospecific antibody binding of the labeled autoantibody was based on variation in equilibrium binding to nonhuman and human red cells of common and rare phenotypes, enhanced binding after red cell protease modification, antiglobulin reactivity of cell-bound IgG comparable to that of cell-bound anti-D, and saturation binding in autoantibody excess. Scatchard analysis of two 125 I-autoantibody preparations yielded site numbers of 41,500 and 53,300 with equilibrium constants of 3.7 and 2.1 X 10(8) L X mol-1. Dog, rabbit, rhesus monkey, and baboon red cells were antigen(s) negative by quantitative adsorption studies adsorbing less than 3% of the labeled autoantibody. Reduced ability of rare human D--red blood cells to adsorb the autoantibody and identification of donor autoantibodies that bind to Rh null red blood cells indicated that eluates contained multiple antibody populations of complex specificities in contrast to anti-D, which consists of a monospecific antibody population. Another difference is that less than 70% of the autoantibody IgG was adsorbed by maximum binding red blood cells as compared with greater than 85% for alloanti-D

  11. Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Onengut, Suna; Chen, Wei-Min

    2015-01-01

    Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array...... and constitute candidates for early screening. Major susceptibility loci for islet autoantibodies are separate from type 1 diabetes risk, which may have consequences for intervention strategies to reduce autoimmunity.......Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array...... and tested for association with seven disease-specific autoantibodies in a large cross-sectional cohort of 6,160 type 1 diabetes-affected siblings. The genetic association with positivity for GAD autoantibodies (GADAs), IA2 antigen (IA-2A), zinc transporter 8, thyroid peroxidase, gastric parietal cells (PCAs...

  12. Islet autoantibody status in a multi-ethnic UK clinic cohort of children presenting with diabetes.

    Science.gov (United States)

    Perchard, R; MacDonald, D; Say, J; Pitts, J; Pye, S; Allgrove, J; Banerjee, K; Amin, R

    2015-04-01

    We prospectively determined islet autoantibody status in children presenting with diabetes to a single UK region in relation to ethnicity. 316 (68.0% non-white) children presenting with diabetes between 2006 and 2013 were tested centrally for islet cell autoantibodies (ICA) and glutamic acid decarboxylase autoantibodies (GAD-65) at diagnosis, and if negative for both, tested for insulin autoantibodies (IAA). The assay used to measure GAD-65 autoantibodies changed from an in-house to a standardised ELISA method during the study. Even with use of the standardised ELISA method, 25.8% of children assigned a diagnosis of type 1 diabetes still tested negative for all three autoantibodies. 30% of children assigned a diagnosis of type 2 diabetes were autoantibody positive, and these had the highest glycated haemoglobin (HbA1c) levels at 12 months follow-up compared with other groups (p value for analysis of variance ethnic group. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program.

    Science.gov (United States)

    Dabelea, D; Ma, Y; Knowler, W C; Marcovina, S; Saudek, C D; Arakaki, R; White, N H; Kahn, S E; Orchard, T J; Goldberg, R; Palmer, J; Hamman, R F

    2014-09-01

    To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program. A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes. The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA(1c), estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56-1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%). These data suggest that 'diabetes autoimmunity', as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  14. Predictors of slow progression to diabetes in children with multiple islet autoantibodies.

    Science.gov (United States)

    Steck, Andrea K; Dong, Fran; Waugh, Kathleen; Frohnert, Brigitte I; Yu, Liping; Norris, Jill M; Rewers, Marian J

    2016-08-01

    Although most children with multiple islet autoantibodies develop type 1 diabetes, rate of progression is highly variable. The goal of this study was to explore potential factors involved in rate of progression to diabetes in children with multiple islet autoantibodies. The Diabetes Autoimmunity Study in the Young (DAISY) has followed 118 children with multiple islet autoantibodies for progression to diabetes. After excluding 27 children currently diabetes-free but followed for 10 years. Islet autoimmunity appeared at 4.0 ± 3.5, 3.2 ± 1.8 and 5.8 ± 3.1 years of age in rapid, moderate and slow progressors, respectively (p = 0.006). Insulin autoantibody levels were lower in slow progressors compared to moderate and rapid progressors. The groups did not differ by gender, ethnicity, family history, susceptibility HLA and non-HLA genes. The rate of development of individual islet autoantibodies including mIAA, GADA, IA-2A and ZnT8A were all slower in the slow versus moderate/rapid progressors. In multivariate analyses, older age at seroconversion and lower initial mIAA levels independently predicted slower progression to diabetes. Later onset of islet autoimmunity and lower autoantibody levels predicted slower progression to diabetes among children with multiple islet autoantibodies. These factors may need to be considered in the design of trials to prevent type 1 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

    Science.gov (United States)

    Gramlich, Oliver W; Beck, Sabine; von Thun Und Hohenstein-Blaul, Nadine; Boehm, Nils; Ziegler, Anika; Vetter, Jan M; Pfeiffer, Norbert; Grus, Franz H

    2013-01-01

    There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group). A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007). Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004). CD27(+) cells and CD27(+)/IgG(+) plasma cells were observed in all glaucomatous subjects, but not in controls. This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an immunological involvement comparable to other

  16. Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

    Directory of Open Access Journals (Sweden)

    Oliver W Gramlich

    Full Text Available BACKGROUND: There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. METHODS AND RESULTS: Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group. A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007. Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004. CD27(+ cells and CD27(+/IgG(+ plasma cells were observed in all glaucomatous subjects, but not in controls. CONCLUSION: This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an

  17. Neural autoantibodies in patients with neurological symptoms and histories of chemical/mold exposures.

    Science.gov (United States)

    Abou-Donia, Mohamed Bahie; Lieberman, Allan; Curtis, Luke

    2018-01-01

    A number of studies have linked exposures to industrial and household chemicals and biological toxins to increased risk of autoimmunity in general and elevated levels of autoantibodies to neural antigens specifically. Elevated neural autoantibodies are biomarkers for many diseases such as multiple sclerosis and Parkinson's disease. Our study reports levels of six types of neural autoantibodies in a group of 24 toxicant-exposed patients. The patients were exposed to a variety of toxicants including contaminated drinking water (four patients), building water/mold damage (eight patients), pesticides (four patients), and other assorted toxic chemicals (eight patients). Levels of all six neural autoantibodies were significantly elevated in most patients and in the patient group at large, with mean antibody levels for the 24 chemically exposed patients (relative to a healthy control population), in descending order: 475% for tau proteins, 391% for microtubule associated proteins-2, 334% for neurofilament proteins (NFP), 302% for myelin basic protein, 299% for glial fibrillary acidic proteins, and 225% for tubulin. Tau protein autoantibodies were significantly elevated in the patient groups with peripheral neuropathy, muscle and joint pain, asthma, and chemical sensitivity. Autoantibodies to tubulin were significantly higher in the chemical sensitivity and asthma patients, autoantibodies to NFP were significantly higher in the patients with sleep apnea, whereas S-100B autoantibodies were significantly increased in patients with muscle/joint pain, asthma, and apnea/insomnia. In patients exposed to environmental toxicants, measurements of autoantibodies may be useful for prevention, diagnosis, and treatment. This study adds to the scientific literature the ability of a broad spectrum of environmental triggers adversely affecting the nervous system through the process of autoimmunity, which may explain the increasing incidence of neurodegenerative diseases.

  18. Autoantibodies to Tumor-Associated Antigens in Epithelial Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Benjamin Piura

    2009-01-01

    Full Text Available This review will focus on recent knowledge related to circulating autoantibodies (AAbs to tumor-associated antigens (TAAs in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7, heat shock proteins (HSP-27, HSP-90, cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1, MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma.

  19. Autoantibodies to plasminogen and their role in tumor diseases.

    Science.gov (United States)

    Goufman, E I; Yakovlev, V N; Tikhonova, N B; Aisina, R B; Yarygin, K N; Mukhametova, L I; Gershkovich, K B; Gulin, D A

    2015-02-01

    Plasma level of IgG autoantibodies to plasminogen was measured by ELISA in patients with benign prostatic hyperplasia (n=25), prostatic cancer (n=17), lung cancer (n=15), and healthy volunteers (n=44). High levels of IgG to plasminogen were found in 2 (12%) of 17 healthy women, in 1 (3.6%) of 27 specimens in a healthy man, in 17 (68%) of 25 specimens in prostatic cancer, in 10 (59%) of 17 specimens in lung cancer, and in 5 (30%) of 15 specimens in benign prostatic hyperplasia. Comparison of plasma levels of anti-plasminogen IgG by affinity chromatography showed 3-fold higher levels in patients with prostatic cancer vs. healthy men.

  20. Time-Encoded Imagers.

    Energy Technology Data Exchange (ETDEWEB)

    Marleau, Peter; Brubaker, Erik

    2014-11-01

    This report provides a short overview of the DNN R&D funded project, Time-Encoded Imagers. The project began in FY11 and concluded in FY14. The Project Description below provides the overall motivation and objectives for the project as well as a summary of programmatic direction. It is followed by a short description of each task and the resulting deliverables.

  1. Encoders and Fault Detection

    NARCIS (Netherlands)

    Persis, Claudio De

    2003-01-01

    Monitoring large-scale systems is of fundamental importance in modern infrastructures. Many of these large-scale systems are complex interconnections of sub-components which interact by means of communication channels with limited bandwidth. Therefore the information must be encoded in order to be

  2. Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy.

    Science.gov (United States)

    Neder, Luciana; Rondon, Daniel A; Cury, Silvana S; Silva, Clovis A da

    2014-01-01

    To evaluate musculoskeletal involvement and autoantibodies in pediatric leprosy patients. 50 leprosy patients and 47 healthy children and adolescents were assessed according to musculoskeletal manifestations (arthralgia, arthritis, and myalgia), musculoskeletal pain syndromes (juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome, and tendinitis), and a panel of autoantibodies and cryoglobulins. Health assessment scores and treatment were performed in leprosy patients. At least one musculoskeletal manifestation was observed in 14% of leprosy patients and in none of the controls. Five leprosy patients had asymmetric polyarthritis of small hands joints. Nerve function impairment was observed in 22% of leprosy patients, type 1 leprosy reaction in 18%, and silent neuropathy in 16%. None of the patients and controls presented musculoskeletal pain syndromes, and the frequencies of all antibodies and cyoglobulins were similar in both groups (p > 0.05). Further analysis of leprosy patients demonstrated that the frequencies of nerve function impairment, type 1 leprosy reaction, and silent neuropathy were significantly observed in patients with versus without musculoskeletal manifestations (p = 0.0036, p = 0.0001, and p = 0.309, respectively), as well as multibacillary subtypes in leprosy (86% vs. 42%, p = 0.045). The median of physicians' visual analog scale (VAS), patients' VAS, pain VAS, and Childhood Health Assessment Questionnaire (CHAQ) were significantly higher in leprosy patients with musculoskeletal manifestations (p = 0.0001, p = 0.002, p = 0002, and p = 0.001, respectively). This was the first study to identify musculoskeletal manifestations associated with nerve dysfunction in pediatric leprosy patients. Hansen's disease should be included in the differential diagnosis of asymmetric arthritis, especially in endemic regions. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  3. CYP2E1 autoantibodies in liver diseases

    Directory of Open Access Journals (Sweden)

    Salvatore Sutti

    2014-01-01

    Full Text Available Autoimmune reactions involving cytochrome P4502E1 (CYP2E1 are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD and chronic hepatitis C (CHC. In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression.

  4. Autoantibodies in serum and sputum from patients with cystic fibrosis.

    Science.gov (United States)

    Schiøtz, P O; Egeskjold, E M; Høiby, N; Permin, H

    1979-10-01

    Sera from 89 patients with cystic fibrosis (CF) and 88 control persons were examined for the occurrence of rheumatoid factors (RF) of the IgG, IgA and IgM classes by an indirect immunofluorescence method and by the latex fixation slide test. The prevalence of RF-IgG was significantly higher (88%) (p less than 0.0005) among the CF patients than among the control persons (7%), while no difference was found between the two groups with regard to RF of the IgA or IgM classes. Fifty-five of the CF patients had chronic Pseudomonas aeruginosa infection in their lungs and two or more precipitins against these bacteria in their sera determined by crossed immunoelectrophoresis. These CF patients did not differ from the 34 CF patients without chronic P. aeruginosa infection, neither with regard to prevalence nor titer of RFs, but there was a positive correlation between the number of P. aeruginosa precipitins in the 55 chronically infected CF patients and their titers of IgG-RF. Nineteen CF patients were examined also for RFs, antinuclear antibodies (ANA) and anti-DNA antibodies in their sputum sol phase and corresponding sera. RFs were demonstrated in the sputum sol phase from 6 of the patients by the latex fixation test, whereas their sera were negative in this test, possibly indicating a local production of RF. Positive reactions for ANA and anti-DNA antibodies were found in 7 and 10 of the sputa respectively, and in higher titers than in the corresponding sera, also suggesting a local production. Titers of autoantibodies in sputum were low and no difference was found between patients with chronic P. aeruginosa infection and patients without P. aeruginosa infection. The possible role of autoantibodies in the patogenesis of pulmonary tissue damage in CF patients is discussed.

  5. Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy

    Directory of Open Access Journals (Sweden)

    Luciana Neder

    2014-09-01

    Full Text Available Objective: To evaluate musculoskeletal involvement and autoantibodies in pediatric leprosy patients. Methods: 50 leprosy patients and 47 healthy children and adolescents were assessed according to musculoskeletal manifestations (arthralgia, arthritis, and myalgia, musculoskeletal pain syndromes (juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome, and tendinitis, and a panel of autoantibodies and cryoglobulins. Health assessment scores and treatment were performed in leprosy patients. Results: At least one musculoskeletal manifestation was observed in 14% of leprosy patients and in none of the controls. Five leprosy patients had asymmetric polyarthritis of small hands joints. Nerve function impairment was observed in 22% of leprosy patients, type 1 leprosy reaction in 18%, and silent neuropathy in 16%. None of the patients and controls presented musculoskeletal pain syndromes, and the frequencies of all antibodies and cyoglobulins were similar in both groups (p > 0.05. Further analysis of leprosy patients demonstrated that the frequencies of nerve function impairment, type 1 leprosy reaction, and silent neuropathy were significantly observed in patients with versus without musculoskeletal manifestations (p = 0.0036, p = 0.0001, and p = 0.309, respectively, as well as multibacillary subtypes in leprosy (86% vs. 42%, p = 0.045. The median of physicians' visual analog scale (VAS, patients' VAS, pain VAS, and Childhood Health Assessment Questionnaire (CHAQ were significantly higher in leprosy patients with musculoskeletal manifestations (p = 0.0001, p = 0.002, p = 0002, and p = 0.001, respectively. Conclusions: This was the first study to identify musculoskeletal manifestations associated with nerve dysfunction in pediatric leprosy patients. Hansen's disease should be included in the differential diagnosis of asymmetric arthritis, especially in endemic regions.

  6. Simultaneous occurrence of foetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    DEFF Research Database (Denmark)

    Morling Taaning, Ellen Birkerod; Jensen, Lise; Varming, Kim

    2012-01-01

    Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia...

  7. Specific presence of intracellular citrullinated proteins in rheumatoid arthritis synovium: relevance to antifilaggrin autoantibodies

    NARCIS (Netherlands)

    Baeten, D.; Peene, I.; Union, A.; Meheus, L.; Sebbag, M.; Serre, G.; Veys, E. M.; de Keyser, F.

    2001-01-01

    OBJECTIVE: To investigate the presence of citrullinated proteins in the synovial membrane of patients with rheumatoid arthritis (RA) and controls, and to analyze a possible relationship with antifilaggrin autoantibody (AFA) reactivity. METHODS: Synovial biopsy samples were obtained from 88

  8. Clinical Significance of Autoantibodies to P53 Protein in Patients with Autoimmune Liver Diseases

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2012-01-01

    Full Text Available Mutations in the p53 gene leading to conformational changes in the p53 protein have been well established in many human cancers. Conformational changes and/or cellular accumulation of the protein may induce an immune response, resulting in circulating autoantibodies to p53, which have been documented in several types of cancers. Although rarely associated with autoimmune disease, a few reports have documented titres of anti-p53 autoantibodies in patients with autoimmune hepatitis and primary biliary cirrhosis. The clinical relevance of circulating autoantibodies to p53, therefore, remains unclear. Accordingly, this study aimed to examine the prevalence and clinical relevance of anti-p53 autoantibodies in patients with selected autoimmune liver diseases.

  9. Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lazaridis, Konstantinos; Dalianoudis, Ioannis; Baltatzidi, Vasiliki; Tzartos, Socrates J

    2017-11-15

    Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Shared Genetic Basis for Type 1 Diabetes, Islet Autoantibodies, and Autoantibodies Associated With Other Immune-Mediated Diseases in Families With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline Anna; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim of this s......Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim...... of this study was to investigate whether susceptibility loci identified in genome-wide association studies (GWAS) of T1D were also associated with autoantibody positivity in individuals with diabetes. Fifty single nucleotide polymorphisms (SNPs) were genotyped in 6,556 multiethnic cases collected by the Type 1...

  11. Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis

    International Nuclear Information System (INIS)

    Fernández Madrid, Félix; Maroun, Marie-Claire; Olivero, Ofelia A; Long, Michael; Stark, Azadeh; Grossman, Lawrence I; Binder, Walter; Dong, Jingsheng; Burke, Matthew; Nathanson, S David; Zarbo, Richard; Chitale, Dhananjay; Zeballos-Chávez, Rocío; Peebles, Carol

    2015-01-01

    The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not

  12. Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

    Science.gov (United States)

    Chruscinski, Andrzej; Huang, Flora Y Y; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C; Kozuszko, Stella; Tinckam, Kathryn J; Rao, Vivek; Dunn, Shannon E; Persinger, Michael A; Levy, Gary A; Ross, Heather J

    2016-01-01

    Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has

  13. Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

    Directory of Open Access Journals (Sweden)

    Andrzej Chruscinski

    Full Text Available Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen. Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient

  14. Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.

    Science.gov (United States)

    Derksen, V F A M; Ajeganova, S; Trouw, L A; van der Helm-van Mil, A H M; Hafström, I; Huizinga, T W J; Toes, R E M; Svensson, B; van der Woude, D

    2017-04-01

    In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

    Science.gov (United States)

    Price, Jordan V.; Haddon, David J.; Kemmer, Dodge; Delepine, Guillaume; Mandelbaum, Gil; Jarrell, Justin A.; Gupta, Rohit; Balboni, Imelda; Chakravarty, Eliza F.; Sokolove, Jeremy; Shum, Anthony K.; Anderson, Mark S.; Cheng, Mickie H.; Robinson, William H.; Browne, Sarah K.; Holland, Steven M.; Baechler, Emily C.; Utz, Paul J.

    2013-01-01

    Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE. PMID:24270423

  16. Hello from the Other Side: How Autoantibodies Circumvent the Blood-Brain Barrier in Autoimmune Encephalitis.

    Science.gov (United States)

    Platt, Maryann P; Agalliu, Dritan; Cutforth, Tyler

    2017-01-01

    Antibodies against neuronal receptors and synaptic proteins are associated with autoimmune encephalitides (AE) that produce movement and psychiatric disorders. In order to exert their pathological effects on neural circuits, autoantibodies against central nervous system (CNS) targets must gain access to the brain and spinal cord by crossing the blood-brain barrier (BBB), a tightly regulated gateway formed by endothelial cells lining CNS blood vessels. To date, the pathogenic mechanisms that underlie autoantibody-triggered encephalitic syndromes are poorly understood, and how autoantibodies breach the barrier remains obscure for almost all AE syndromes. The relative importance of cellular versus humoral immune mechanisms for disease pathogenesis also remains largely unexplored. Here, we review the proposed triggers for various autoimmune encephalopathies and their animal models, as well as basic structural features of the BBB and how they differ among various CNS regions, a feature that likely underlies some regional aspects of autoimmune encephalitis pathogenesis. We then discuss the routes that antibodies and immune cells employ to enter the CNS and their implications for AE. Finally, we explore future therapeutic strategies that may either preserve or restore barrier function and thereby limit immune cell and autoantibody infiltration into the CNS. Recent mechanistic insights into CNS autoantibody entry indicate promising future directions for therapeutic intervention beyond current, short-lived therapies that eliminate circulating autoantibodies.

  17. Hello from the Other Side: How Autoantibodies Circumvent the Blood–Brain Barrier in Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    Tyler Cutforth

    2017-04-01

    Full Text Available Antibodies against neuronal receptors and synaptic proteins are associated with autoimmune encephalitides (AE that produce movement and psychiatric disorders. In order to exert their pathological effects on neural circuits, autoantibodies against central nervous system (CNS targets must gain access to the brain and spinal cord by crossing the blood–brain barrier (BBB, a tightly regulated gateway formed by endothelial cells lining CNS blood vessels. To date, the pathogenic mechanisms that underlie autoantibody-triggered encephalitic syndromes are poorly understood, and how autoantibodies breach the barrier remains obscure for almost all AE syndromes. The relative importance of cellular versus humoral immune mechanisms for disease pathogenesis also remains largely unexplored. Here, we review the proposed triggers for various autoimmune encephalopathies and their animal models, as well as basic structural features of the BBB and how they differ among various CNS regions, a feature that likely underlies some regional aspects of autoimmune encephalitis pathogenesis. We then discuss the routes that antibodies and immune cells employ to enter the CNS and their implications for AE. Finally, we explore future therapeutic strategies that may either preserve or restore barrier function and thereby limit immune cell and autoantibody infiltration into the CNS. Recent mechanistic insights into CNS autoantibody entry indicate promising future directions for therapeutic intervention beyond current, short-lived therapies that eliminate circulating autoantibodies.

  18. Beta-cell autoantibodies and their function in Taiwanese children with type 1 diabetes mellitus.

    Science.gov (United States)

    Tung, Yi-Ching; Chen, Mei-Huei; Lee, Cheng-Ting; Tsai, Wen-Yu

    2009-11-01

    To understand the importance of autoimmunity in the development of type 1 diabetes in Taiwanese children, we evaluated the presence of beta-cell autoantibodies and their correlation with residual beta-cell function. From 1989 to 2006, 157 Taiwanese children with newly diagnosed type 1 diabetes were enrolled in this study. We determined the presence of beta-cell autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), insulinoma antigen 2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs). A 6-minute glucagon test was also performed at diagnosis. At diagnosis, 73% of children tested positive for GADAs, 76% for IA-2As and 21% for IAAs. Ninety-two percent of them had at least one of the beta-cell autoantibodies detected. Positivity for IAAs was more frequent in patients younger than 5 years than in those older than 5 years (45% vs. 13%). Using multiple regression analysis, the presence of GADAs or IAAs, or age of onset of these patients was an independent factor for residual beta-cell function. Younger patients and those with GADAs had less residual beta-cell function at disease onset, whereas those with IAAs had more insulin reserve. Autoimmunity plays an important role in the pathogenesis of type 1 diabetes in Taiwanese children, and the presence of IAAs tends to be more common in younger children.

  19. Troponin and anti-troponin autoantibody levels in patients with ventricular noncompaction.

    Directory of Open Access Journals (Sweden)

    Hatice Betül Erer

    Full Text Available Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24 and noncompaction with reduced EF (LVEF <35%, n = 26 groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group, troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG. Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.

  20. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...

  1. Cognitive functions and autoantibodies in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Anna Bogaczewicz

    2016-06-01

    Full Text Available Introduction: Autoantibodies may occur in the course of various diseases. In the case of systemic lupus erythematosus the presence of specific autoantibodies is included in the classification criteria of the disease. The aim of the study was to investigate whether the presence of the serologic markers of systemic lupus erythematosus, i.e. anti-dsDNA, anti-Sm and anticardiolipin antibodies of the class IgM and IgG are linked with the results of neuropsychological tests evaluating selected cognitive functions in patients without overt neuropsychiatric lupus and without antiphospholipid syndrome. Material and methods: The study included 22 patients with systemic lupus erythematosus. For the assessment of anti-dsDNA, anti-Sm and anticardiolipin antibodies the immunoenzymatic method was used. For neuropsychological estimation of the selected cognitive functions the attention switching test and the choice reaction time were applied, in which the results are expressed as the average delay i.e. mean correct latency, using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB. Results: The results of attention switching test in patients with anti-Sm antibodies were lower, but not significantly different from those obtained by the patients without such antibodies: 75.0 (73.12–88.12 vs. 92.5 (85–95. Choice reaction time was significantly longer in patients with anti-Sm antibodies in comparison to the patients without antiSm antibodies: 614.9 (520.6–740.8 vs. 476.7 (396.6–540 (p = 0.01. No significant difference was demonstrated in the results of attention switching test and choice reaction time with regard to the presence of anti-dsDNA antibodies. The results of attention switching test and choice reaction time were not different between the groups of patients with and without anticardiolipin antibodies in the IgM and IgG class. Conclusions: Anti-Sm antibodies seem to contribute to

  2. Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis.

    LENUS (Irish Health Repository)

    Gunawardena, H

    2009-06-01

    OBJECTIVE: The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140-kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland. METHODS: Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140-kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation\\/immunodepletion, using commercial monoclonal antibodies to NXP-2, reference anti-p140, and anti-p155\\/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects. RESULTS: Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti-p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM-overlap syndrome or control subjects. No anti-p140 antibody-positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP-2 (the previously identified MJ autoantigen). In children with anti-p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0-16.1). The clinical features of patients with anti-p140 autoantibodies were different from those of children with anti-p155\\/140 autoantibodies. The presence of HLA-DRB1*08 was a possible risk factor for anti-p140 autoantibody positivity. CONCLUSION: This study has established that anti-p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the

  3. Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests

    OpenAIRE

    Egerer, Karl; Roggenbuck, Dirk; Hiemann, Rico; Weyer, Max-Georg; Büttner, Thomas; Radau, Boris; Krause, Rosemarie; Lehmann, Barbara; Feist, Eugen; Burmester, Gerd-Rüdiger

    2010-01-01

    Introduction Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of autoantibody IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated. Methods Autoantibody...

  4. Disorders of phonological encoding.

    Science.gov (United States)

    Butterworth, B

    1992-03-01

    Studies of phonological disturbances in aphasic speech are reviewed. It is argued that failure to test for error consistency in individual patients makes it generally improper to draw inferences about specific disorders of phonological encoding. A minimalist interpretation of available data on phonological errors is therefore proposed that involves variable loss of information in transmission between processing subsystems. Proposals for systematic loss or corruption of phonological information in lexical representations or in translation subsystems is shown to be inadequately grounded. The review concludes with some simple methodological prescriptions for future research.

  5. Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease.

    Science.gov (United States)

    Lin, Jiunn-Diann; Wang, Yuan-Hung; Fang, Wen-Fang; Hsiao, Chia-Jung; Chagnaadorj, Amarzaya; Lin, Yuh-Feng; Tang, Kam-Tsun; Cheng, Chao-Wen

    2016-11-01

    This study investigated the association of serum B-lymphocyte activating factor (BAFF) levels with autoimmune thyroid disease (AITD) in a Chinese population. We enrolled 221 patients with AITD [170 patients with Graves' disease (GD), 51 patients with Hashimoto's thyroiditis (HT)], and 124 healthy controls. Serum BAFF levels, thyroid function and thyroid autoantibody (TAb) levels, including of thyroid-stimulating hormone receptor antibody (TSHRAb), anti-thyroid peroxidase antibody (Anti-TPO Ab), and antithyroglobulin antibody (ATA), were measured at baseline. Serum BAFF levels were higher in the GD, HT, and AITD groups than in the control group. Significant correlations were observed between BAFF and TSHRAb levels (r=0.238, p=0.018), between BAFF and Anti-TPO Ab levels (p=0.038), and between BAFF and ATA titers (p=0.025) in women but not in men. In addition, serum BAFF levels were significantly associated with free thyroxine (r=0.430, p=0.004) and TSHRAb (r=0.495, p=0.001) levels in women with active GD but not in those with inactive GD. Serum BAFF levels are increased in GD, HT, and AITD. The correlation between serum BAFF and TAb levels exhibits a dimorphic pattern, particularly in active GD. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Autoantibodies and immunoglobulins among atomic-bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Carter, R.L.; Akiyama, Mitoshi

    1993-06-01

    The purpose of this study was to determine if exposure to atomic-bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody, and immunoglobulin levels (IgG, IgM, IgA, and IgE) were measured among 2061 Adult Health Study participants in Hiroshima and Nagasaki from December 1987 to November 1989. The prevalence and titers of rheumatoid factor increased in a statistically significant manner with increasing radiation dose. No radiation effect was found on the prevalence of antinuclear antibody, antithyroglobulin antibody, and anti-thyroid-microsomal antibody. A statistically significant relationship was also found between radiation exposure and the IgA level in females and the IgM levels in both sexes-both levels increased as radiation dose increased. However, the effects of radiation exposure were not large and accounted for less than 10% of the total variation in each measurement. Levels of IgG and IgE were not affected by radiation exposure. (author)

  7. Autoantibodies to vimentin cause accelerated rejection of cardiac allografts.

    Science.gov (United States)

    Mahesh, Balakrishnan; Leong, Hon-Sing; McCormack, Ann; Sarathchandra, Padmini; Holder, Angela; Rose, Marlene L

    2007-04-01

    Autoimmune responses to vimentin occur after solid organ transplantation, but their pathogenic effects are unclear. The aim of these studies was to investigate the effects of vimentin preimmunization on allogeneic and isografted hearts in a murine transplant model. Immunization of C57BL/6 mice with murine vimentin in complete Freund's adjuvant resulted in anti-vimentin antibodies and vimentin-reactive Th-1 cells. Transplantation of 129/sv hearts into vimentin-immunized C57BL/6 recipients resulted in accelerated rejection (8.4 +/- 1.5 days; n = 18), compared with hen egg lysozyme-immunized C57BL/6 (13.3 +/- 2.2 days; n = 10; P rejection, shown by the fact that vimentin-immunized B-cell-deficient IgH6 mice did not show accelerated rejection of 129/sv allografts, but rejection was restored by adoptive transfer of serum containing anti-vimentin antibodies. Eluates from donor hearts placed in vimentin/complete Freund's adjuvant recipients contained anti-vimentin antibodies, shown by Western blotting. Confocal imaging of rejected hearts de-monstrated presence of vimentin and C3d on apoptosed leukocytes, endothelial cells, and platelet/leukocyte conjugates. These results demonstrate that autoantibodies to vimentin, in conjunction with the alloimmune response, have a pathogenic role in allograft rejection.

  8. Thyroid Dysfunction and Autoantibodies Association with Hypertensive Disorders during Pregnancy

    Directory of Open Access Journals (Sweden)

    Azin Alavi

    2012-01-01

    Full Text Available Background. Thyroid dysfunction and autoimmunity are relatively common in reproductive age and have been associated with adverse health outcomes for both mother and child, including hypertensive disorders during pregnancy. Objective. To survey the relation between thyroid dysfunction and autoimmunity and incidence and severity of pregnancy-induced hypertensive disorders. Method. In this case control study 48 hypertensive patients in 4 subgroups (gestational hypertension, mild preeclampsia, severe preeclampsia, eclampsia and 50 normotensive ones were studied. The samples were nulliparous and matched based on age and gestational age and none of them had previous history of hypertensive or thyroid disorders and other underlying systemic diseases or took medication that might affect thyroid function. Their venous blood samples were collected using electrochemiluminescence and ELISA method and thyroid hormones and TSH and autoantibodies were measured. Results. Hypertensive patients had significant lower T3 concentration compared with normotensive ones with mean T3 values 152.5±48.93 ng/dL, 175.36±58.07 ng/dL respectively. Anti-TPO concentration is higher in control group 6.07±9.02 IU/mL compared with 2.27±2.94 IU/mL in cases. Conclusion. The severity of preeclampsia and eclampsia was not associated with thyroid function tests. The only significant value was low T3 level among pregnancy, induced hypertensive patients.

  9. Recognition and Relevance of Anti-DFS70 Autoantibodies in Routine Antinuclear Autoantibodies Testing at a Community Hospital

    Directory of Open Access Journals (Sweden)

    John B. Carter

    2018-04-01

    Full Text Available Antinuclear autoantibodies (ANA displaying a dense fine speckled pattern (DFS, ICAP AC-2 on HEp-2 cells are frequently observed in clinical laboratory referrals, often associated with anti-DFS70 specificity. Anti-DFS70 positive patients rarely develop systemic autoimmune rheumatic disease (SARD, especially in the absence of clinical evidence or additional anti-extractable nuclear antigen (ENA antibodies, prompting suggestions that an isolated DFS70-specific ENA may be an exclusionary finding for SARD. In this study, the frequency and diagnostic significance of anti-DFS70 autoantibodies was investigated in a community hospital cohort of patients undergoing routine ANA testing. ANA screening was performed by HEp-20-10-based indirect immunofluorescence, followed by ENA profiling using a multiparametric line immunoassay (LIA. Of 6,511 patient samples tested for ANA in 2016, the DFS pattern was identified in 1,758 (27.0%, 720 (41.0% of which were anti-DFS70 positive by LIA. Of these, 526 (73.1% revealed isolated anti-DFS70 reactivity, while 194 (26.9% showed additional ENA specificities. Among 1,038 anti-DFS70 negative or borderline samples, 778 (75.0% were ENA profile negative, while the remaining 260 (25.0% showed a varied presence of other ENA specificities. Chart reviews of patients with an isolated anti-DFS70 ANA affirmed that ANA-related SARD is rare in the absence of clinical evidence or other ENA specificities, there being no case thus far identified. Rheumatoid arthritis patients occasionally had an isolated anti-DFS70 ANA and were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. In conclusion, the recognition of a DFS ANA pattern using a mitotic-rich HEp-2 substrate, followed by confirmation of anti-DFS70 specificity should be a routine ANA testing service. Use of an expanded ENA profile and clinical correlation is necessary to affirm the “isolation” of anti-DFS70 as the cause of an ANA. Recognition of

  10. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    2010-05-01

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  11. Intestinal inflammation influences α-MSH reactive autoantibodies: relevance to food intake and body weight.

    Science.gov (United States)

    Coquerel, Quentin; Sinno, Maria Hamze; Boukhettala, Nabile; Coëffier, Moïse; Terashi, Mutsumi; Bole-Feysot, Christine; Breuillé, Denis; Déchelotte, Pierre; Fetissov, Sergueï O

    2012-01-01

    Autoantibodies reacting with alpha-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are involved in regulation of feeding. In this work we studied if intestinal inflammation (mucositis) may influence α-MSH autoantibodies production relevant to food intake and body weight. Mucositis and anorexia were produced in Sprague-Dawley rats by methotrexate (MTX, 2.5mg/kg/day, for three days, subcutaneously). Plasma levels of total IgG and of α-MSH autoantibodies were measured during and after MTX-induced mucositis and were compared with pair-fed and ad libitum-fed controls. Effects of intraperitoneal injections of rabbit anti-α-MSH IgG (3 or 10 μg/day/rat) on MTX-induced anorexia and on plasma α-MSH peptide concentration were separately studied. Here we show that in MTX rats, intestinal mucositis and anorexia were accompanied by decreased plasma levels of both total IgG and of α-MSH autoantibodies while refeeding was characterized by their elevated levels. In spite of similar food intake in MTX and pair-fed rats, recovery of body weight was delayed by at least 1 week in the MTX group. During refeeding and body weight deficit in MTX rats, α-MSH IgG autoantibody levels correlated negatively with food to water intake ratios. Injections of anti-α-MSH IgG induced a dose-dependent attenuation of food intake and body weight regain in MTX-treated rats accompanied by increased concentrations of α-MSH peptide which correlated positively with plasma levels of α-MSH autoantibodies. These data show that intestinal inflammation, independently from food restriction, affects general humoral immune response which may influence food intake and body weight control via modulation of α-MSH plasma concentration by α-MSH reactive autoantibodies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Flow cytometric immunobead assay for quantitative detection of platelet autoantibodies in immune thrombocytopenia patients.

    Science.gov (United States)

    Zhai, Juping; Ding, Mengyuan; Yang, Tianjie; Zuo, Bin; Weng, Zhen; Zhao, Yunxiao; He, Jun; Wu, Qingyu; Ruan, Changgeng; He, Yang

    2017-10-23

    Platelet autoantibody detection is critical for immune thrombocytopenia (ITP) diagnosis and prognosis. Therefore, we aimed to establish a quantitative flow cytometric immunobead assay (FCIA) for ITP platelet autoantibodies evaluation. Capture microbeads coupled with anti-GPIX, -GPIb, -GPIIb, -GPIIIa and P-selectin antibodies were used to bind the platelet-bound autoantibodies complex generated from plasma samples of 250 ITP patients, 163 non-ITP patients and 243 healthy controls, a fluorescein isothiocyanate (FITC)-conjugated secondary antibody was the detector reagent and mean fluorescence intensity (MFI) signals were recorded by flow cytometry. Intra- and inter-assay variations of the quantitative FCIA assay were assessed. Comparisons of the specificity, sensitivity and accuracy between quantitative and qualitative FCIA or monoclonal antibody immobilization of platelet antigen (MAIPA) assay were performed. Finally, treatment process was monitored by our quantitative FCIA in 8 newly diagnosed ITPs. The coefficient of variations (CV) of the quantitative FCIA assay were respectively 9.4, 3.8, 5.4, 5.1 and 5.8% for anti-GPIX, -GPIb, -GPIIIa, -GPIIb and -P-selectin autoantibodies. Elevated levels of autoantibodies against platelet glycoproteins GPIX, GPIb, GPIIIa, GPIIb and P-selectin were detected by our quantitative FCIA in ITP patients compared to non-ITP patients or healthy controls. The sensitivity, specificity and accuracy of our quantitative assay were respectively 73.13, 81.98 and 78.65% when combining all 5 autoantibodies, while the sensitivity, specificity and accuracy of MAIPA assay were respectively 41.46, 90.41 and 72.81%. A quantitative FCIA assay was established. Reduced levels of platelet autoantibodies could be confirmed by our quantitative FCIA in ITP patients after corticosteroid treatment. Our quantitative assay is not only good for ITP diagnosis but also for ITP treatment monitoring.

  13. Anti-neurotrophic effects from autoantibodies in adult diabetes having primary open angle glaucoma or dementia

    Directory of Open Access Journals (Sweden)

    Mark B Zimering

    2013-05-01

    Full Text Available Aims: To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets of diabetes having open- angle glaucoma, dementia or control subjects.Methods: Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies' neurite inhibitory effect was investigated in coincubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing.Results: Diabetic primary open angle glaucoma or suspects (n=20 or diabetic dementia (n=3 autoantibodies caused significantly greater mean inhibition of neurite outgrowth in PC12 cells (p < .0001 compared to autoantibodies in control diabetic (n=24 or nondiabetic (n=10 subjects without glaucoma (p < .01. Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10 µM concentrations of Y27632 (n=4. It was substantially reduced by 30 mM concentrations of sodium chlorate (n=4. Peak, long-lasting activity survived storage x 5 years at 0-4 deg C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n=5 caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5 µM concentrations of Y27632. Conclusion: These data suggest that autoantibodies in adult diabetes having primary open angle glaucoma (glaucoma suspects and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve activation of the RhoA/p160 ROCK signaling pathway.

  14. Nanocrystal-encoded fluorescent microbeads for proteomics: antibody profiling and diagnostics of autoimmune diseases.

    Science.gov (United States)

    Sukhanova, Alyona; Susha, Andrei S; Bek, Alpan; Mayilo, Sergiy; Rogach, Andrey L; Feldmann, Jochen; Oleinikov, Vladimir; Reveil, Brigitte; Donvito, Beatrice; Cohen, Jacques H M; Nabiev, Igor

    2007-08-01

    The first application of nanocrystal (NC)-encoded microbeads to clinical proteomics is demonstrated by multiplexed detection of circulating autoantibodies, markers of systemic sclerosis. Two-color complexes, consisting of NC-encoded, antigen-covered beads, anti-antigen antibody or clinical serum samples, and dye-tagged detecting antibodies, were observed using flow cytometry assays and on the surface of single beads. The results of flow cytometry assays correlated with the ELISA technique and provided clear discrimination between the sera samples of healthy donors and patients with autoimmune disease. Microbead fluorescence signals exhibited narrow distribution regardless of their surface antigen staining, without the need of any fluorescence compensation-a parameter determining the limit of sensitivity of flow cytometry assays. In single bead measurements, less than 30 dye-labeled antibodies interacting with the topoI-specific antibodies at the surface of a bead have been detected by the emission of dye excited through the FRET from NCs. In this format, the antibody-bead interaction reaction turns specifically the fluorescence signal from dye label off and on, additionally increasing autoantibody detection sensitivity.

  15. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer.

    Science.gov (United States)

    Milne, Katy; Barnes, Rebecca O; Girardin, Adam; Mawer, Melanie A; Nesslinger, Nancy J; Ng, Alvin; Nielsen, Julie S; Sahota, Robert; Tran, Eric; Webb, John R; Wong, May Q; Wick, Darin A; Wray, Andrew; McMurtrie, Elissa; Köbel, Martin; Kalloger, Steven E; Gilks, C Blake; Watson, Peter H; Nelson, Brad H

    2008-01-01

    Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy.

  16. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC. A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B and other immunological markers (CD20, MHC class I and MHC class II. Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35 of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004. Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant

  17. Time encoded radiation imaging

    Science.gov (United States)

    Marleau, Peter; Brubaker, Erik; Kiff, Scott

    2014-10-21

    The various technologies presented herein relate to detecting nuclear material at a large stand-off distance. An imaging system is presented which can detect nuclear material by utilizing time encoded imaging relating to maximum and minimum radiation particle counts rates. The imaging system is integrated with a data acquisition system that can utilize variations in photon pulse shape to discriminate between neutron and gamma-ray interactions. Modulation in the detected neutron count rates as a function of the angular orientation of the detector due to attenuation of neighboring detectors is utilized to reconstruct the neutron source distribution over 360 degrees around the imaging system. Neutrons (e.g., fast neutrons) and/or gamma-rays are incident upon scintillation material in the imager, the photons generated by the scintillation material are converted to electrical energy from which the respective neutrons/gamma rays can be determined and, accordingly, a direction to, and the location of, a radiation source identified.

  18. Encoding the Factorisation Calculus

    Directory of Open Access Journals (Sweden)

    Reuben N. S. Rowe

    2015-08-01

    Full Text Available Jay and Given-Wilson have recently introduced the Factorisation (or SF- calculus as a minimal fundamental model of intensional computation. It is a combinatory calculus containing a special combinator, F, which is able to examine the internal structure of its first argument. The calculus is significant in that as well as being combinatorially complete it also exhibits the property of structural completeness, i.e. it is able to represent any function on terms definable using pattern matching on arbitrary normal forms. In particular, it admits a term that can decide the structural equality of any two arbitrary normal forms. Since SF-calculus is combinatorially complete, it is clearly at least as powerful as the more familiar and paradigmatic Turing-powerful computational models of Lambda Calculus and Combinatory Logic. Its relationship to these models in the converse direction is less obvious, however. Jay and Given-Wilson have suggested that SF-calculus is strictly more powerful than the aforementioned models, but a detailed study of the connections between these models is yet to be undertaken. This paper begins to bridge that gap by presenting a faithful encoding of the Factorisation Calculus into the Lambda Calculus preserving both reduction and strong normalisation. The existence of such an encoding is a new result. It also suggests that there is, in some sense, an equivalence between the former model and the latter. We discuss to what extent our result constitutes an equivalence by considering it in the context of some previously defined frameworks for comparing computational power and expressiveness.

  19. Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering

    Science.gov (United States)

    Spindler, Volker; Rötzer, Vera; Dehner, Carina; Kempf, Bettina; Gliem, Martin; Radeva, Mariya; Hartlieb, Eva; Harms, Gregory S.; Schmidt, Enno; Waschke, Jens

    2013-01-01

    In pemphigus vulgaris, a life-threatening autoimmune skin disease, epidermal blisters are caused by autoantibodies primarily targeting desmosomal cadherins desmoglein 3 (DSG3) and DSG1, leading to loss of keratinocyte cohesion. Due to limited insights into disease pathogenesis, current therapy relies primarily on nonspecific long-term immunosuppression. Both direct inhibition of DSG transinteraction and altered intracellular signaling by p38 MAPK likely contribute to the loss of cell adhesion. Here, we applied a tandem peptide (TP) consisting of 2 connected peptide sequences targeting the DSG adhesive interface that was capable of blocking autoantibody-mediated direct interference of DSG3 transinteraction, as revealed by atomic force microscopy and optical trapping. Importantly, TP abrogated autoantibody-mediated skin blistering in mice and was effective when applied topically. Mechanistically, TP inhibited both autoantibody-induced p38 MAPK activation and its association with DSG3, abrogated p38 MAPK-induced keratin filament retraction, and promoted desmosomal DSG3 oligomerization. These data indicate that p38 MAPK links autoantibody-mediated inhibition of DSG3 binding to skin blistering. By limiting loss of DSG3 transinteraction, p38 MAPK activation, and keratin filament retraction, which are hallmarks of pemphigus pathogenesis, TP may serve as a promising treatment option. PMID:23298835

  20. Neuronal Surface Autoantibodies in Neuropsychiatric Disorders: Are There Implications for Depression?

    Directory of Open Access Journals (Sweden)

    Shenghua Zong

    2017-07-01

    Full Text Available Autoimmune diseases are affecting around 7.6–9.4% of the general population. A number of central nervous system disorders, including encephalitis and severe psychiatric disorders, have been demonstrated to associate with specific neuronal surface autoantibodies (NSAbs. It has become clear that specific autoantibodies targeting neuronal surface antigens and ion channels could cause severe mental disturbances. A number of studies have focused or are currently investigating the presence of autoantibodies in specific mental conditions such as schizophrenia and bipolar disorders. However, less is known about other conditions such as depression. Depression is a psychiatric disorder with complex etiology and pathogenesis. The diagnosis criteria of depression are largely based on symptoms but not on the origin of the disease. The question which arises is whether in a subgroup of patients with depression, the symptoms might be caused by autoantibodies targeting membrane-associated antigens. Here, we describe how autoantibodies targeting membrane proteins and ion channels cause pathological effects. We discuss the physiology of these antigens and their role in relation to depression. Finally, we summarize a number of studies detecting NSAbs with a special focus on cohorts that include depression diagnosis and/or show depressive symptoms.

  1. Prevalence of thyroid function test abnormalities and thyroid autoantibodies in children with vitiligo

    Directory of Open Access Journals (Sweden)

    Fatma Sule Afsar

    2013-01-01

    Full Text Available Although the exact pathogenic processes involved in vitiligo are still unknown, its association with autoimmune disorders and endocrine dysfunction has been reported. One of its associations is with thyroid diseases. The purpose of this retrospective study was to determine the prevalence of thyroid function tests and thyroid autoantibody abnormalities in children diagnosed with vitiligo and compare the results with the literature. The laboratory documents of thyroid function tests (FT3, FT4, and TSH and thyroid autoantibodies (TgAb and TPOAb belonging to the pediatric vitiligo patients were studied retrospectively. Thyroid function tests and thyroid autoantibody abnormalities were detected in 20 (25.3% of the pediatric vitiligo patients. Thirteen (16.4% patients were evaluated as subclinical hypothyroidism, two (2.5% were evaluated as hypothyroidism, and five (6.3% were evaluated as euthyroidism. Thyroid autoantibodies were found to be positive in nine (11.3% patients. Previously reported prevalence of thyroid disease in children with vitiligo ranged from 10.7 to 24.1%, and the prevalence of 25.3% determined in this study was compatible with the literature. Also, the high rate of subclinical hypothyroidism determined in these patients attracted attention to the probable development of overt hypothyroidism in a long term. Thus, our results suggest that thyroid function tests and thyroid autoantibodies should be analyzed in children with vitiligo.

  2. Association of Autoantibodies to BP180 with Disease Activity in Greek Patients with Bullous Pemphigoid

    Directory of Open Access Journals (Sweden)

    Aikaterini Patsatsi

    2012-01-01

    Full Text Available 39 bullous pemphigoid (BP patients were studied to assess the clinical significance of anti-BP180 and anti-BP230 circulating autoantibodies of BP and correlate their titers with the clinical scores of the BP Disease Area Index (BPDAI and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS as well as with the intensity of pruritus measured by the BPDAI pruritus component. All parameters were evaluated by the time of diagnosis (baseline, month 3, and month 6. Titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (, and ABSIS (, values, as well as with BPDAI component for the intensity of pruritus (, at baseline. At month 3, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (, and ABSIS (, values, as well as with the BPDAI component for the intensity of pruritus (, . At month 6, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (, and ABSIS (, values, as well as with the BPDAI component for the intensity of pruritus (, . There was no statistically significant correlation between titers of anti-BP230 autoantibodies and the BPDAI, ABSIS, and BPDAI component for the intensity of pruritus at the same time points.

  3. Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody exacerbated by epstein-barr virus.

    Science.gov (United States)

    Fadeyi, Emmanuel A; Simmons, Julie H; Jones, Mary Rose; Palavecino, Elizabeth L; Pomper, Gregory J

    2015-01-01

    Most cases of autoimmune hemolytic anemia (AIHA) are caused by the production of an autoantibody that targets determinants on red blood cells (RBCs). This autoantibody can be immunoglobulin (Ig) G, IgM, or IgA. Some autoantibodies react optimally at 0° to 4°C (ie, cold agglutinin) and usually are clinically insignificant. High-titer cold agglutinins are associated with IgM autoantibody and complement fixation induced by infectious agents, including the Epstein-Barr virus (EBV). This case report describes a 31-year-old man who had jaundice, a hemoglobin of 6.0 gdL, and was diagnosed with a hemolytic crisis of AIHA. He received a total of 11 RBC transfusions during a 15-hour period without sustained response and later died. The direct antiglobulin test results for this patient were positive, whereas the cold-agglutinin-testing results were negative. We detected EBV DNA in blood via polymerase chain reaction (PCR). We report a rare case of AIHA associated with an IgG autoantibody and exacerbated by EBV infection, causing a fatal hemolytic anemia. Copyright© by the American Society for Clinical Pathology (ASCP).

  4. Rare myositis-specific autoantibody associations among Hungarian patients with idiopathic inflammatory myopathy

    Directory of Open Access Journals (Sweden)

    Levente Bodoki

    2015-10-01

    Full Text Available Idiopathic inflammatory myopathies are systemic, chronic autoimmune diseases characterized by symmetrical, proximal muscle weakness. Homogeneous groups present with similar symptoms. The response to therapy and prognosis could be facilitated by myositis-specific autoantibodies, and in this way, give rise to immunoserological classification. The myositis-specific autoantibodies are directed against specific proteins found in the cytoplasm or in the nucleus of the cells. To date, literature suggests the rarity of the co-existence of two myositis-specific autoantibodies. In this study the authors highlight rare associations of myositis-specific autoantibodies. Three hundred and thirty-seven Hungarian patients with polymyositis or dermatomyositis were studied. Their clinical findings were noted retrospectively. Specific blood tests identified six patients with the rare co-existence of myositis-specific autoantibodies, anti-Jo-1 and anti-SRP, anti-Jo-1 and anti-Mi-2, anti-Mi-2 and anti-PL-12, anti-Mi-2 and anti-SRP, and anti-SRP and anti-PL-7, respectively. This case review aims to identify the clinical importance of these rare associations and their place within the immunoserological classification.

  5. Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Nathan Karin

    2018-03-01

    Full Text Available We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoantibodies are high-affinity neutralizing antibodies. Based on animal models studies, we suggested that they participate in the regulation of cancer and autoimmunity, albeit at the level of their production cannot entirely prevent the development and progression of these diseases. We have, therefore, named this selective breakdown of tolerance as “Beneficial Autoimmunity.” Despite its beneficial outcome, this process is likely to be stochastic and not directed by a deterministic mechanism, and is likely to be associated with the dominant expression of these inflammatory mediators at sites that are partially immune privileged. A recent study conducted on autoimmune regulator-deficient patients reported that in human this type of breakdown of B cell tolerance is T cell dependent. This explains, in part, why the response is highly restricted, and includes high-affinity antibodies. The current mini-review explores this subject from different complementary perspectives. It also discusses three optional translational aspects: amplification of autoantibody production as a therapeutic approach, development of autoantibody based diagnostic tools, and the use of B cells from donors that produce these autoantibodies for the development of high-affinity human monoclonal antibodies.

  6. Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility

    Science.gov (United States)

    Jin, Hui; Arase, Noriko; Hirayasu, Kouyuki; Kohyama, Masako; Suenaga, Tadahiro; Saito, Fumiji; Tanimura, Kenji; Matsuoka, Sumiko; Ebina, Kosuke; Shi, Kenrin; Toyama-Sorimachi, Noriko; Yasuda, Shinsuke; Horita, Tetsuya; Hiwa, Ryosuke; Takasugi, Kiyoshi; Ohmura, Koichiro; Yoshikawa, Hideki; Saito, Takashi; Atsumi, Tatsuya; Sasazuki, Takehiko; Katayama, Ichiro; Lanier, Lewis L.; Arase, Hisashi

    2014-01-01

    Specific HLA class II alleles are strongly associated with susceptibility to rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to RA has remained unclear. Recently, we found a unique function of HLA class II molecules: their ability to aberrantly transport cellular misfolded proteins to the cell surface without processing to peptides. Rheumatoid factor (RF) is an autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected in 70–80% of RA patients but also in patients with other diseases. Here, we report that intact IgG heavy chain (IgGH) is transported to the cell surface by HLA class II via association with the peptide-binding groove and that IgGH/HLA class II complexes are specifically recognized by autoantibodies in RF-positive sera from RA patients. In contrast, autoantibodies in RF-positive sera from non-RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for that allele’s association with RA was observed (r = 0.81; P = 4.6 × 10−5). Our findings suggest that IgGH complexed with certain HLA class II alleles is a target for autoantibodies in RA, which might explain why these HLA class II alleles confer susceptibility to RA. PMID:24567378

  7. Autoantibodies in children with juvenile dermatomyositis: A single centre experience from North-West India.

    Science.gov (United States)

    Hussain, Altaf; Rawat, Amit; Jindal, Ankur Kumar; Gupta, Anju; Singh, Surjit

    2017-05-01

    The objective of this study is to determine autoantibody profile in children with juvenile dermatomyositis (JDM). Children who were diagnosed with JDM (either recently diagnosed during the study period or follow-up patients) were included in the study. Autoantibodies were detected with commercially available Immunodot kit. Thirty patients were included in the study. Nine out of thirty patients (30%) were positive for one of the 12 autoantibodies tested. Anti-SRP antibody was most common antibody detected in 3 patients followed by anti-MDA-5 antibody in 2 patients; while anti-Jo1 antibody, anti-TIF1-γ antibody, anti-Mi-2 antibody, and anti-PM-Scl antibody were positive in 1 patient each. A different disease phenotype was observed with each autoantibody. The patient with anti-Jo1 antibody had a severe systemic disease in the form of interstitial lung disease; patients with anti-MDA-5 antibody and anti-Mi2 antibody had more severe skin disease with mild muscle disease and patients with anti-SRP antibody had significant skin and muscle disease. Anti-TIF1-γ and anti-PM-Scl antibodies were seen in patients with features of overlap syndrome (myositis-scleroderma). Estimation of autoantibodies may serve as an adjunct tool in delineating and defining distinct clinical phenotypes in children diagnosed with juvenile dermatomyositis. They may also help in prognostication.

  8. Anti-oxLDL autoantibodies and their correlation with lipid profile and nutritional status in adolescents.

    Science.gov (United States)

    Sanches, Leticia B; da Silva, Isis T; Paz, Aline F S; Fisberg, Mauro; Cintra, Isa P; Villar, Betzabeth S; Damasceno, Nágila R T

    2008-01-01

    To investigate whether levels of autoantibodies to oxidized LDL (anti-oxLDL) in the plasma of adolescents correlates with their anthropometric measurements and lipid profiles. The study enrolled 150 adolescents aged between 10 and 15 years, recruited from the obesity clinic at Universidade Federal de São Paulo (SP) and from public schools in Piracicaba, SP, Brazil. Anthropometric measurements such as body mass index and waist and arm circumferences were used to classify the adolescents as having healthy weight, overweight or obesity. Colorimetric enzymatic methods were used for biochemical lipid profile analysis and ELISA was used to determine anti-oxLDL autoantibody levels. Analysis of anthropometric variables indicated that the obese group's profile was abnormal compared to the healthy weight and overweight groups (p cardiovascular risk. Analysis of the lipid profiles demonstrated statistically significant differences in concentrations of total cholesterol (p = 0.011), HDL-cholesterol (p = 0.001) and LDL-cholesterol (p < 0.042) between the healthy weight group and the obese group. Analysis of plasma anti-oxLDL autoantibodies demonstrated that the overweight (p = 0.012) and obese groups (p < 0.001) had higher values than the healthy weight group. There were also correlations between anti-oxLDL autoantibody levels and anthropometric variables. In adolescents the presence of anti-oxLDL autoantibodies and metabolic changes to the lipid profile vary in proportion with anthropometric parameters, which makes anti-oxLDL concentration a potential biochemical indicator of risk of metabolic syndrome.

  9. Functional autoantibodies targeting G protein-coupled receptors in rheumatic diseases.

    Science.gov (United States)

    Cabral-Marques, Otavio; Riemekasten, Gabriela

    2017-11-01

    G protein-coupled receptors (GPCRs) comprise the largest and most diverse family of integral membrane proteins that participate in different physiological processes such as the regulation of the nervous and immune systems. Besides the endogenous ligands of GPCRs, functional autoantibodies are also able to bind GPCRs to trigger or block intracellular signalling pathways, resulting in agonistic or antagonistic effects, respectively. In this Review, the effects of functional GPCR-targeting autoantibodies on the pathogenesis of autoimmune diseases, including rheumatic diseases, are discussed. Autoantibodies targeting β1 and β2 adrenergic receptors, which are expressed by cardiac and airway smooth muscle cells, respectively, have an important role in the development of asthma and cardiovascular diseases. In addition, high levels of autoantibodies against the muscarinic acetylcholine receptor M3 as well as those targeting endothelin receptor type A and type 1 angiotensin II receptor have several implications in the pathogenesis of rheumatic diseases such as Sjögren syndrome and systemic sclerosis. Expanding the knowledge of the pathophysiological roles of autoantibodies against GPCRs will shed light on the biology of these receptors and open avenues for new therapeutic approaches.

  10. Association of susceptible genetic markers and autoantibodies in ...

    Indian Academy of Sciences (India)

    alleles that encode a conserved sequence of amino acids,. (70QRRAA74, 70RRRAA74 or 70QKRAA74) consist of residues 70–74 in the third hyper variable region (HVR3) of the DRb1 chain (Gregersen et al. 1987). These residues constitute a helical domain forming one side of the antigen binding site, a site likely to affect ...

  11. p53 autoantibodies, cytokine levels and ovarian carcinogenesis.

    Science.gov (United States)

    Tsai-Turton, Miyun; Santillan, Antonio; Lu, Dan; Bristow, Robert E; Chan, Kwun C; Shih, Ie-Ming; Roden, Richard B S

    2009-07-01

    To address the hypothesis that type II ovarian carcinoma, mutation of p53 and plasma levels of particular cytokines are associated with the generation of p53-specific serum autoantibody (AAb) responses in patients. Levels of CA125, 17 cytokines and AAbs to tumor-associated antigens including p53 were measured in plasma of 130 gynecologic tumor patients and 84 healthy controls. TP53 exons 4-9 were sequenced in tumor specimens. p53 AAbs are associated with high grade, but not low grade ovarian carcinoma. Seropositivity for p53 AAb occurred only in those ovarian carcinoma patients whose tumors contained mutated TP53, regardless of the exon targeted. Higher p53 AAb levels were detected in ovarian carcinoma patients who had higher stage disease, but p53 AAb levels were not correlated with CA125 levels. Among high-grade carcinoma patients, there was no relationship between p53 AAb seropositivity and seropositivity to other tumor-associated antigens tested, CA125 level or survival outcome. Both high and low grade ovarian carcinoma patients exhibited elevated levels of IL6, IL8 and IL10 as compared to healthy volunteers, although increased levels of IL5, MCP1, MIP1 and TNFalpha were associated only with high grade and advanced disease. Higher levels of p53AAb responses were correlated with elevated circulating IL4 and IL12, but reduced IL8 levels. Type II, but not type I, ovarian carcinoma patients had elevated serum levels of p53 AAb. P53 AAb is associated with mutation of TP53, higher plasma IL4 and IL12 but lower plasma IL8 levels and no survival advantage.

  12. Frequency of glutamic acid decarboxylase autoantibodies in Mexican diabetic children.

    Science.gov (United States)

    Mendoza-Morfín, F; Curiel-Pérez, M O; Cárdenas-Tirado, H; Montero-González, P; Gutiérrez-Avila, C; Bravo-Ríos, L E; Cárdenas-Cornejo, I; Normandía-Almeida, M A

    2000-01-01

    Use radio binding assay (RBA) to quantify the frequency of autoantibodies to glutamic acid decarboxylase in Mexican children with type 1 diabetes mellitus (DM 1). GAD antibodies were measured in 140 mestizo children with DM 1, 66 female (47.14%) and 74 male (52.8%); age 11.7 +/- 3.55 years, and range 1.10 to 18.5 years. Most patients were treated with intermediate acting insulin, and some with the former combined with regular insulin. Mean disease duration was 3.11 +/- 2.94 years, and range 1 month to 14.5 years. Once the signed written consent was obtained, a 5.0-mL blood sample was drawn, immediately centrifuged, and the serum was kept frozen to -20 degrees C until RBA evaluation was performed with a commercial kit. The anti-GAD was positive in 76 DM 1 patients (54.28%) with values from 1.11 to 156.73 U/mL, and negative in 64 (45.71%). In 19 positive anti-GAD patients, the test was repeated and levels were found between 1.38 and 156.62 U/mL. An initial control group consisting of 25 healthy non-related volunteers matched by sex and age, showed negative anti-GAD for all. The frequency of anti-GAD in these patients was lower than that of the DM 1 European patients, but similar to that of Asians. This supports the heterogeneity of the etiopathogenic factors of DM 1 in different ethnic groups.

  13. Zinc transporter 8 autoantibodies assessment in daily practice.

    Science.gov (United States)

    Hussein, Hala; Ibrahim, Fidaa; Sobngwi, Eugène; Gautier, Jean François; Boudou, Philippe

    2017-01-01

    Zinc transporter 8 (ZnT8) is specifically expressed in the pancreatic β-cell and is more restricted in its tissue distribution than other auto-antigens as glutamic acid decarboxylase 65 (GAD 65 ) and insulinoma-associated antigen-2 (IA2). ZnT8 autoantibodies (ZnT8A) assessment allows identifying rapid progression to clinical onset of the disease. We evaluated the prevalence of ZnT8A in adults of different ethnic and phenotypic groups and analyzed its potential utility as additional marker of autoimmunity in daily practice. ZnT8A, GADA and IA2A were assessed using enzyme-linked immune-sorbent assay (ELISA) in 160 controls and 216 diabetic subjects. 105 were of type 1 diabetes (T1D), 17 had Latent Autoimmune Diabetes of Adults (LADA), 38 were type 2 diabetic (T2D) and 56 had ketosis-prone diabetes (KPD). 82 patients were newly diagnosed cases. ZnT8A were detected in 1% of controls and were not found in any of our 38 T2D subjects or 56 KPD subjects. In contrast, ZnT8A were detected in 18% of LADA subjects and in 38% of T1D subjects. A slight difference of percentage of ZnT8A positivity was found among our T1D ethnic groups. ZnT8A were positive in 41% of patients positive for GADA and 67% of patients positive for IA2A. The percentage of stratification achieved 91% when GADA, IA2A and ZnT8A were assessed simultaneously. Results obtained for ZnT8A measurement using ELISA were consistent with previous data. Such investigation could improve the risk stratification and would be integrated in our daily practice. Copyright © 2016. Published by Elsevier Inc.

  14. Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis

    Directory of Open Access Journals (Sweden)

    Junko Inagaki

    2004-01-01

    Full Text Available Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, α1, β1 and γ1 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-α1, -β1 and -γ1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-α1, -β1 and -γ1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of α1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with –mouse— laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

  15. Selecting Operations for Assembler Encoding

    Directory of Open Access Journals (Sweden)

    Tomasz Praczyk

    2010-04-01

    Full Text Available Assembler Encoding is a neuro-evolutionary method in which a neural network is represented in the form of a simple program called Assembler Encoding Program. The task of the program is to create the so-called Network Definition Matrix which maintains all the information necessary to construct the network. To generate Assembler Encoding Programs and the subsequent neural networks evolutionary techniques are used.
    The performance of Assembler Encoding strongly depends on operations used in Assembler Encoding Programs. To select the most effective operations, experiments in the optimization and the predator-prey problem were carried out. In the experiments, Assembler Encoding Programs equipped with different types of operations were tested. The results of the tests are presented at the end of the paper.

  16. Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care

    DEFF Research Database (Denmark)

    Schou, M; Sæther, S G; Borowski, K

    2016-01-01

    BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated...... the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD......)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti-neuronal autoantibodies were found in 11...

  17. Identification of autoantibodies to tyrosil-tRNA synthetase in heart disfunctions

    Directory of Open Access Journals (Sweden)

    Ryabenko D. V.

    2010-09-01

    Full Text Available Aim. To investigate the levels of specific autoantibodies against tyrosyl-tRNA synthetase and its individual modules in the blood serum of people with heart failure caused by dilated cardiomyopathy, myocarditis and ischemic heart disease compared with healthy donors. Methods. Recombinant proteins were obtained using bacterial strains transformed with appropriate plasmid vectors and were purified by chromatography on Ni-NTA-agarose. The levels of specific autoantibodies were investigated by ELISA. Results. The increased levels of autoantibodies specific to tyrosyl-tRNA synthetase, its N-terminal catalytic module and non-catalytic C-module, were found in the blood serum of patients, compared with healthy donors. Conclusions. The results obtained demonstrate the possible role of tyrosyl-tRNA synthetase in adaptive changes of the myocardium in response to stress factors.

  18. Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera.

    Directory of Open Access Journals (Sweden)

    Eric Nagele

    Full Text Available After decades of Alzheimer's disease (AD research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease.

  19. First results with a radioreceptor-assay (TRAK-Assay) for TSH-receptor-autoantibodies

    International Nuclear Information System (INIS)

    Becker, W.; Reiners, C.; Boerner, W.

    1983-01-01

    A new radioreceptor-assay (TRAK-assay) for autoantibodies against TSH-receptors was tested in 48 untreated thyrotoxic patients (26 regional autonomies, 22 toxic diffuse goiters). None of the 26 patients with regional autonomy showed positive autoantibody-titers. 4 patients with toxic diffuse goiter and thyrotoxic exophthalmos were TRAK-positive. Positive titers of microsomal and thyreoglobulin autoantibodies could be seen in 8 of 9 patients with positive TRAK-titers. In accordance with the conventional methods for detecting thyroid-stimulating immunoglobulins the new TRAK-assay seems to be suited for differentiating between immunogenic toxic diffuse goiter (Graves' disease) and goiter with disseminated autonomy as well as for prediction of relapse. (orig.) [de

  20. Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with pemphigus vulgaris and foliaceus and in healthy relatives

    NARCIS (Netherlands)

    Torzecka, Jolanta Dorota; Narbutt, Joanna; Sysa-Jedrzejowska, Anna; Waszczykowska, Elzbieta; Lukamowicz, Jolanta; Pas, Hendri H.

    2003-01-01

    BACKGROUND: Pemphigus is a life-threatening, autoimmune blistering disease, mediated by IgG autoantibodies. The aim of our study was to assess the usefulness of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating pemphigus autoantibodies, and to compare its sensitivity and

  1. Circulating pemphigus autoantibodies in healthy relatives of pemphigus patients : coincidental phenomenon with a risk of disease development?

    NARCIS (Netherlands)

    Torzecka, Jolanta Dorota; Wozniak, Katarzyna; Kowalewski, Cezary; Waszczykowska, Elrbieta; Sysa-Jedrzejowska, Anna; Pas, Hendri H.; Narbutt, Joanna

    Pemphigus is a severe autoimmune disease characterized by circulating and bound in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur in healthy first-degree relatives of pemphigus patients; however, their significance is not fully elucidated. Thus, the aim of the study was

  2. Clinical utility of anti-p53 auto-antibody: systematic review and focus on colorectal cancer.

    Science.gov (United States)

    Suppiah, Aravind; Greenman, John

    2013-08-07

    Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 auto-antibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses on the data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.

  3. A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity.

    Science.gov (United States)

    El Rahman, Heba Allah Abd; Salama, Mohamed; Gad El-Hak, Seham A; El-Harouny, Mona A; ElKafrawy, Passent; Abou-Donia, Mohamed B

    2018-02-01

    In the present study, we screened the sera of subjects chronically exposed to mixtures of pesticides (composed mainly of organophosphorus compounds (OPs) and others) and developed neurological symptoms for the presence of autoantibodies against cytoskeletal neural proteins. OPs have a well-characterized clinical profile resulting from acute cholinergic crisis. However, some of these compounds cause neuronal degeneration and demyelination known as organophosphorus compound-induced delayed neurotoxicity (OPIDN) and/or organophosphorus compound-induced chronic neurotoxicity (OPICN). Studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins against cytoskeletal neural proteins in patients with chemical-induced brain injury. In this study, we screened the serum of 50 pesticide-exposed subjects and 25 non-exposed controls, using Western blot analysis against the following proteins: neurofilament triplet proteins (NFPs), tubulin, microtubule-associated tau proteins (Tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII), glial S100-B protein, and alpha-synuclein (SNCA). Serum reactivity was measured as arbitrary chemiluminescence units. As a group, exposed subjects had significantly higher levels of autoantibody reactivity in all cases examined. The folds of increase in of autoantibodies against neural proteins of the subjects compared to healthy humans in descending order were as follows: MBP, 7.67, MAG 5.89, CaMKII 5.50, GFAP 5.1, TAU 4.96, MAP2 4.83, SNCA 4.55, NFP 4.55, S-100B 2.43, and tubulin 1.78. This study has demonstrated the presence of serum autoantibodies to central nervous system-specific proteins in a group of farmers chronically exposed to pesticides who developed neurological signs and symptoms of neural injury. These autoantibodies can be used as future diagnostic

  4. Development and validation of a high throughput system for discovery of antigens for autoantibody detection.

    Directory of Open Access Journals (Sweden)

    Isabel K Macdonald

    Full Text Available An assay employing a panel of tumor-associated antigens has been validated and is available commercially (EarlyCDT®-Lung to aid the early detection of lung cancer by measurement of serum autoantibodies. The high throughput (HTP strategy described herein was pursued to identify new antigens to add to the EarlyCDT-Lung panel and to assist in the development of new panels for other cancers. Two ligation-independent cloning vectors were designed and synthesized, producing fusion proteins suitable for the autoantibody ELISA. We developed an abridged HTP version of the validated autoantibody ELISA, determining that results reflected the performance of the EarlyCDT assay, by comparing results on both formats. Once validated this HTP ELISA was utilized to screen multiple fusion proteins prepared on small-scale, by a HTP expression screen. We determined whether the assay performance for these HTP protein batches was an accurate reflection of the performance of R&D or commercial batches. A HTP discovery platform for the identification and optimal production of tumor-associated antigens which detects autoantibodies has been developed and validated. The most favorable conditions for the exposure of immunogenic epitopes were assessed to produce discriminatory proteins for use in a commercial ELISA. This process is rapid and cost-effective compared to standard cloning and screening technologies and enables rapid advancement in the field of autoantibody assay discovery. This approach will significantly reduce timescale and costs for developing similar panels of autoantibody assays for the detection of other cancer types with the ultimate aim of improved overall survival due to early diagnosis and treatment.

  5. Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center.

    Science.gov (United States)

    Artim-Esen, Bahar; Çene, Erhan; Şahinkaya, Yasemin; Ertan, Semra; Pehlivan, Özlem; Kamali, Sevil; Gül, Ahmet; Öcal, Lale; Aral, Orhan; Inanç, Murat

    2014-07-01

    Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

  6. Coeliac disease-specific autoantibodies targeted against transglutaminase 2 disturb angiogenesis

    Science.gov (United States)

    Myrsky, E; Kaukinen, K; Syrjänen, M; Korponay-Szabó, I R; Mäki, M; Lindfors, K

    2008-01-01

    Coeliac disease is characterized by immunoglobulin-A (IgA)-class autoantibodies targeted against transglutaminase 2 (TG2), a multi-functional protein also with a role in angiogenesis. These antibodies are present in patient serum but are also found bound to TG2 below the epithelial basement membrane and around capillaries in the small intestinal mucosa. Based on these facts and the information that the mucosal vasculature of coeliac patients on a gluten-containing diet is disorganized, we studied whether the coeliac disease-specific autoantibodies targeted against TG2 would disturb angiogenesis. The effects of coeliac disease-specific autoantibodies on in vitro angiogenesis were studied in angiogenic cell cultures. The binding of the antibodies to cells, endothelial sprouting, migration of both endothelial and vascular mesenchymal cells, the integrity of the actin cytoskeleton in both cell types and the differentiation of vascular mesenchymal cells were recorded. In vitro, IgA derived from coeliac disease patients on a gluten-containing diet binds to surface TG2 on endothelial and vascular mesenchymal cells and this binding can be inhibited by the removal of TG2. In addition, coeliac disease-specific autoantibodies targeting TG2 disturb several steps of angiogenesis: endothelial sprouting and the migration of both endothelial and vascular mesenchymal cells. Furthermore, the autoantibodies cause disorganization of the actin cytoskeleton in both capillary cell types that account most probably for the defective cellular migration. We conclude that coeliac disease-specific autoantibodies recognizing TG2 inhibit angiogenesis in vitro. This disturbance of the angiogenic process could lead in vivo to the disruption of the mucosal vasculature seen in coeliac disease patients on a gluten-containing diet. PMID:18279443

  7. Polyclonal hypergammaglobulinemia and autoantibody production induced by vaccination in farmed Atlantic salmon.

    Science.gov (United States)

    Satoh, Minoru; Bjerkås, Inge; Haugarvoll, Erlend; Chan, Edward K L; Szabo, Nancy J; Jirillo, Emilio; Poppe, Trygve T; Sveier, Harald; Tørud, Brit; Koppang, Erling O

    2011-01-01

    The introduction of oil-adjuvanted vaccines in salmon aquaculture made large-scale production feasible by reducing the impact of infections. Vaccines given intraperitoneally (ip) contain oil adjuvant such as mineral oil. However, in rodents, a single ip injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome. We have recently reported that autoimmune disease in farmed salmon, characterized by production of various autoantibodies, immune complex glomerulonephritis, liver thrombosis, and spinal deformity, are previously unrecognized side effects of vaccination. In the present study, we examined whether vaccination-induced autoantibody production in farmed Atlantic salmon is a mere result of polyclonal B-cell activation. Sera were collected from 205 vaccinated and unvaccinated Atlantic salmon (experimental, 7 farms) and wild salmon. Total IgM levels and autoantibodies to salmon blood cell (SBC) extract in sera were measured by ELISA and the relationship between hypergammaglobulinemia and autoantibody production was analyzed. Comparison of endpoint titers vs levels/units using a single dilution of sera in detection of autoantibodies to SBC showed near perfect correlation, justifying the use of the latter for screening. Both total IgM and anti-SBC antibodies are increased in vaccinated salmon compared with unvaccinated controls, however, they do not always correlate well when compared between groups or between individuals, suggesting the involvement of antigen-specific mechanisms in the production of anti-SBC autoantibodies. The primary considerations of successful vaccine for aquaculture are cost-effectiveness and safety. Vaccination-induced autoimmunity in farmed Atlantic salmon may have consequences on future vaccine development and salmon farming strategy. Evaluation for polyclonal hypergamamglobulinemia and autoimmunity should be included as an important trait when vaccine efficacy and safety are evaluated in future. Copyright © 2011

  8. Analysis of novel Sjogren's syndrome autoantibodies in patients with dry eyes.

    Science.gov (United States)

    Everett, Sandra; Vishwanath, Sahana; Cavero, Vanessa; Shen, Long; Suresh, Lakshmanan; Malyavantham, Kishore; Lincoff-Cohen, Norah; Ambrus, Julian L

    2017-03-07

    Dry eye is a common problem in Ophthalmology and may occur for many reasons including Sjogren's syndrome (SS). Recent studies have identified autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP), which occur early in the course of SS. The current studies were designed to evaluate how many patients with idiopathic dry eye and no evidence of systemic diseases from a dry eye practice have these autoantibodies. Patients from a dry eye clinic and normal controls were assessed by Schirmer's test for tear flow. Sera were assessed for autoantibodies using ELISA assays. Statistics was performed with Prism 7 software and student's unpaired t test. In this study 60% of the dry eye patients expressed one of these autoantibodies. Only 30% expressed one of the autoantibodies associated with long-standing SS, which are included in the diagnostic criteria for SS, anti-Ro and anti-La. Patients with disease for less than 2 years and mild dry eyes did not express anti-Ro or anti-La, while 25% expressed anti-SP1. Similar observations, with smaller numbers, were made when patients had not only dry eye but also dry mouth. Antibodies to SP1, CA6 and PSP occur in some patients with idiopathic dry eyes. Further studies will be needed to determine how many of these patients go on to develop systemic manifestations of SS. Testing for these autoantibodies may allow early recognition of patients with SS. This will lead to improved management of the patients and the development of new strategies to maintain normal lacrimal and salivary gland function in patients with SS.

  9. IL‐6‐specific autoantibodies among APECED and thymoma patients

    Science.gov (United States)

    Pihlap, Maire; Ranki, Annamari; Krohn, Kai; Trebusak Podkrajsek, Katarina; Bratanic, Nina; Battelino, Tadej; Willcox, Nick; Peterson, Pärt; Kisand, Kai

    2016-01-01

    Introduction Both autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) and the rare thymoma patients with chronic mucocutaneous candidiasis (CMC) have neutralizing autoantibodies to Th17 cytokines and significant defects in production of IL‐22 and IL‐17F by their T cells. The cause of these defects is unknown. We hypothesized that they might result from autoimmunity against upstream cytokines normally responsible for generating and maintaining Th17 cells. Methods Luciferase immunoprecipitation (LIPS) was used to screen for autoantibodies to IL‐6, IL‐1β, TGF‐β3, IL‐21, and IL‐23 in patients with APECED or thymoma. We used Western blotting to assess the conformation‐dependence of the IL‐6 autoantibodies and flow cytometric analysis of intracellular phospho‐STAT3 induction to assess IL‐6‐neutralizing capacity in IgGs isolated from patient and control sera. We also used Luminex xMAP to measure serum cytokine levels. Results We found autoantibodies binding to conformational epitopes of IL‐6 in 19.5% of 41 patients with APECED and 12.5% of 104 with thymoma—especially in those with long disease durations. The autoantibodies were predominantly of IgG1 subclass and failed to neutralize IL‐6 activity. Notably, serum levels of the IL‐6 and IL‐17A cytokines were higher in anti‐IL‐6 seropositive than—negative APECED patients or healthy controls. We also detected autoantibody binding to IL‐23 in 27.9% of thymoma patients, resulting from cross‐recognition through the p40 subunit it shares with IL‐12. Conclusions IL‐6 and IL‐17A elevation in these seropositive patients suggests that antibody‐binding may protect IL‐6 from degradation and prolong its half‐life in vivo. PMID:27957331

  10. Lack of association between folate-receptor autoantibodies and neural-tube defects.

    LENUS (Irish Health Repository)

    Molloy, Anne M

    2009-07-09

    BACKGROUND: A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as compared with 10% of controls. We sought to confirm this finding in an Irish population, which traditionally has had a high prevalence of neural-tube defects. METHODS: We performed two studies. Study 1 consisted of analysis of stored frozen blood samples collected from 1993 through 1994 from 103 mothers with a history of pregnancy complicated by a neural-tube defect (case mothers), 103 mothers with a history of pregnancy but no complication by a neural-tube defect (matched with regard to number of pregnancies and sampling dates), 58 women who had never been pregnant, and 36 men. Study 2, conducted to confirm that the storage of samples did not influence the folate-receptor autoantibodies, included fresh samples from 37 case mothers, 22 control mothers, 10 women who had never been pregnant, and 9 men. All samples were assayed for blocking and binding autoantibodies against folate receptors. RESULTS: In Study 1, blocking autoantibodies were found in 17% of case mothers, as compared with 13% of control mothers (odds ratio, 1.54; 95% confidence interval [CI], 0.70 to 3.39), and binding autoantibodies in 29%, as compared with 32%, respectively (odds ratio, 0.82; 95% CI, 0.44 to 1.50). Study 2 showed similar results, indicating that sample degradation was unlikely. CONCLUSIONS: The presence and titer of maternal folate-receptor autoantibodies were not significantly associated with a neural-tube defect-affected pregnancy in this Irish population.

  11. Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

    DEFF Research Database (Denmark)

    Burford, B; Gentry-Maharaj, A; Graham, R

    2013-01-01

    Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed...... these autoantibodies in large population cohorts of sera taken before cancer diagnosis....

  12. AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    N. V. Piven

    2011-01-01

    Full Text Available Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to glutamic acid decarboxylase by means of ELISA approach. (Med. Immunol., 2011, vol. 13, N 2-3, pp 257-260

  13. Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.

    Science.gov (United States)

    Haddon, D James; Diep, Vivian K; Price, Jordan V; Limb, Cindy; Utz, Paul J; Balboni, Imelda

    2015-06-17

    Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n = 45) to healthy controls (n = 17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n = 23) and without significant renal involvement (n = 18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n = 23) and longitudinal samples (88 patient visits) to test its accuracy. Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B cell-activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV and X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative

  14. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher M.; Carlsen, Jørn

    2010-01-01

    Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides...... be differentiated by a profile of autoantibodies binding to 28 proteins or their peptides. The informative autoantibody profile included down-regulation as well as up-regulation of both IgM and IgG specific reactivities. This profile was evaluated for robustness using a panel of six independent test patients...

  15. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis.

    Science.gov (United States)

    Kreye, Jakob; Wenke, Nina K; Chayka, Mariya; Leubner, Jonas; Murugan, Rajagopal; Maier, Nikolaus; Jurek, Betty; Ly, Lam-Thanh; Brandl, Doreen; Rost, Benjamin R; Stumpf, Alexander; Schulz, Paulina; Radbruch, Helena; Hauser, Anja E; Pache, Florence; Meisel, Andreas; Harms, Lutz; Paul, Friedemann; Dirnagl, Ulrich; Garner, Craig; Schmitz, Dietmar; Wardemann, Hedda; Prüss, Harald

    2016-10-01

    SEE ZEKERIDOU AND LENNON DOI101093/AWW213 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesias, and seizures. Little is known about the cerebrospinal fluid autoantibody repertoire. Antibodies against the NR1 subunit of the NMDAR are thought to be pathogenic; however, direct proof is lacking as previous experiments could not distinguish the contribution of further anti-neuronal antibodies. Using single cell cloning of full-length immunoglobulin heavy and light chain genes, we generated a panel of recombinant monoclonal NR1 antibodies from cerebrospinal fluid memory B cells and antibody secreting cells of NMDAR encephalitis patients. Cells typically carried somatically mutated immunoglobulin genes and had undergone class-switching to immunoglobulin G, clonally expanded cells carried identical somatic hypermutation patterns. A fraction of NR1 antibodies were non-mutated, thus resembling 'naturally occurring antibodies' and indicating that tolerance induction against NMDAR was incomplete and somatic hypermutation not essential for functional antibodies. However, only a small percentage of cerebrospinal fluid-derived antibodies reacted against NR1. Instead, nearly all further antibodies bound specifically to diverse brain-expressed epitopes including neuronal surfaces, suggesting that a broad repertoire of antibody-secreting cells enrich in the central nervous system during encephalitis. Our functional data using primary hippocampal neurons indicate that human cerebrospinal fluid-derived monoclonal NR1 antibodies alone are sufficient to cause neuronal surface receptor downregulation and subsequent impairment of NMDAR-mediated currents, thus providing ultimate proof of antibody pathogenicity. The observed formation of immunological memory might be relevant for clinical relapses. © The Author (2016). Published by Oxford University Press on

  16. Use of self-collected capillary blood samples for islet autoantibody screening in relatives: a feasibility and acceptability study.

    Science.gov (United States)

    Liu, Y; Rafkin, L E; Matheson, D; Henderson, C; Boulware, D; Besser, R E J; Ferrara, C; Yu, L; Steck, A K; Bingley, P J

    2017-07-01

    To evaluate the feasibility of using self-collected capillary blood samples for islet autoantibody testing to identify risk in relatives of people with Type 1 diabetes. Participants were recruited via the observational TrialNet Pathway to Prevention study, which screens and monitors relatives of people with Type 1 diabetes for islet autoantibodies. Relatives were sent kits for capillary blood collection, with written instructions, an online instructional video link and a questionnaire. Sera from capillary blood samples were tested for autoantibodies to glutamic acid decarboxylase, islet antigen-2, insulin and zinc transporter 8. 'Successful' sample collection was defined as obtaining sufficient volume and quality to provide definitive autoantibody results, including confirmation of positive results by repeat assay. In 240 relatives who returned samples, the median (range) age was 15.5 (1-49) years and 51% were male. Of these samples, 98% were sufficient for glutamic acid decarboxylase, islet antigen-2 and zinc transporter 8 autoantibody testing and 84% for insulin autoantibody testing and complete autoantibody screen. The upper 90% confidence bound for unsuccessful collection was 4.4% for glutamic acid decarboxylase, islet antigen-2 and/or zinc transporter 8 autoantibody assays, and 19.3% for insulin autoantibodies. Despite 43% of 220 questionnaire respondents finding capillary blood collection uncomfortable or painful, 82% preferred home self-collection of capillary blood samples compared with outpatient venepuncture (90% of those aged 18 years). The perceived difficulty of collecting capillary blood samples did not affect success rate. Self-collected capillary blood sampling offers a feasible alternative to venous sampling, with the potential to facilitate autoantibody screening for Type 1 diabetes risk. © 2017 Diabetes UK.

  17. Calcium-sensing receptor autoantibodies and idiopathic hypoparathyroidism.

    Science.gov (United States)

    Tomar, Neeraj; Gupta, Nandita; Goswami, Ravinder

    2013-09-01

    Data on calcium-sensing receptor autoantibodies (CaSRAbs) in hypoparathyroidism are variable. We assessed the prevalence and significance of CaSRAbs in idiopathic hypoparathyroidism. This was a case-control study. One hundred forty-seven patients with idiopathic hypoparathyroidism treated during 1998-2011 in a tertiary care setting and 348 controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic lymphocytic thyroiditis (CLT), n = 50] participated in the study. CaSRAb assays included Western blot with CaSR protein expressed in Escherichia coli or human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro-transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR. Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR genes were sequenced for mutations. E coli-Western blot assay revealed 16.3% CaSRAb positivity in idiopathic hypoparathyroidism, which was comparable with healthy subjects and CLT but significantly less than the T1DM controls. The prevalence of CaSRAbs on HEK293-Western blot (24.5%) against 150 kDa and/or 168 kDa protein in hypoparathyroidism was significantly higher than the healthy subjects, T1DM, and CLT. IP assay showed CaSRAbs in 12.9% of the hypoparathyroid patients but not in controls. The sensitivity and specificity of CaSRAbs in E coli and HEK-293-CaSR Western blot and IP assays were 16.3% and 83.1%, 24.5% and 88.9%, and 12.9% and 100%, respectively, and 42.1% of the cases detected were common in the IP assay and HEK293-Western blot. Duration of illness and coexistent autoimmunity were similar in patients with and without CaSRAbs. The CaSRAb-positive sera showed no immunofluorescence and phosphorylated ERK1/2 activity. The CaSR gene sequence was normal in all patients. One of the patients showed a novel p.Met1_Asp6del mutation in the signal peptide region of the PTH gene. IP performed the best in detecting CaSRAbs in 12.9% of hypoparathyroid patients

  18. Peri-encoding predictors of memory encoding and consolidation.

    Science.gov (United States)

    Cohen, Noga; Pell, Liat; Edelson, Micah G; Ben-Yakov, Aya; Pine, Alex; Dudai, Yadin

    2015-03-01

    We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis

    DEFF Research Database (Denmark)

    Wichman, Johanna Eva Märta; Winther, Kristian Hillert; Bonnema, Steen Joop

    2016-01-01

    3366 records. Controlled trials in adults (≥18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects...

  20. Pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis and potential targets for biologic treatment

    NARCIS (Netherlands)

    Sanders, J.S.F.; Abdulahad, W H; Stegeman, C A; Kallenberg, C G M

    2014-01-01

    Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are autoimmune diseases in which the small vessels are inflamed. Clinical observations suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data and animal models, particularly for

  1. Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Mari R. Thomas

    2015-08-01

    Conclusions: Anti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP.

  2. [Significance of non-organ-specific autoantibodies in HCV-related chronic hepatitis].

    Science.gov (United States)

    Guidi, Marcello; Muratori, Paolo; Granito, Alessandro; Muratori, Luigi; Pappas, Georgios; Bianchi, Francesco B

    2005-12-01

    The preliminary question regarding the clinical issue of the antiviral therapy in the HCV related chronic hepatitis patients is: is it mandatory the research for the autoantibodies in the eligible patients for the antiviral treatment? This issue is of particular interest at the light of the the reported cases of HCV positive patients with positivity for liver kidney microsome type 1 antibody who developed a hepatitic flare during the antiviral treatment. The data from literature about the efficacy and safety on the antiviral treatment in patients with autoantibodies are few and controversial, particularly if the ones regarding antiviral drugs and more recent treatment regimens are taking into account (peg-interferon, combined therapy of interferon and ribavirin). Large and prospective studies are needed for a thorough evaluation about the potential impact of autoantibodies reactivity on the therapeutic outcome. To date, it must be confirmed that a strict monitoring of hepatic parameters is to recommend during the whole treatment phase. This in the light of a potential appearance of significant flares of aminotransferases, particularly in subjects with anti LKM-1 autoantibodies, during interferon therapy.

  3. Patients with systemic vasculitis have increased levels of autoantibodies against oxidized LDL

    NARCIS (Netherlands)

    Swets, BP; Brouwer, DAJ; Tervaert, JWC

    Oxidation of low density lipoprotein (LDL) is considered to play an important role in the development of atherosclerosis and increased levels of autoantibodies against oxidized LDL have been found in patients with various manifestations of atherosclerosis. Patients with vasculitis are prone to the

  4. Screening for autoantibodies in patients with primary fibromyalgia syndrome and a matched control group

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Høyer-Madsen, M; Danneskiold-Samsøe, B

    1990-01-01

    Primary fibromyalgia syndrome (PFS) is a non-articular rheumatic condition characterized by chronic muscular pain. We have performed screening for autoantibodies in 20 women with PFS and in 19 age-matched healthy women. Fifty-five percent of the PFS patients had anti-smooth muscle antibodies and 40...

  5. Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Jørgensen, P E

    1995-01-01

    We have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The study was focused on organs known to contain EGF or its receptor. Compared with controls, the offspring of autoimmune rats had a higher perinatal mortality and...

  6. Autoantibodies Against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ahmet Menteşe

    2017-12-01

    Full Text Available Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML and to provide a novel perspective regarding the autoimmune basis of the disease. Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers. Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively. A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001. Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

  7. Autoimmune hemolytic anemia, as part of Evans' syndrome, caused by cold reactive IgG autoantibodies

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

    We describe a boy with Evans' syndrome, consisting of immune thrombocytopenic purpura at age 2 and autoimmune hemolytic anemia (AIHA) at age 4. AIHA was caused by cold Ige autoantibodies. This is unusual because AIHA is generally associated with either warm IgG antibodies or cold IgM antibodies.

  8. Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) with unusual manifestations and without detectable autoantibodies

    OpenAIRE

    Jimena Sanz-Bueno; Daniella Cullen; Carlos Zarco; Francisco Vanaclocha

    2014-01-01

    We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS) secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.

  9. Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus with unusual manifestations and without detectable autoantibodies

    Directory of Open Access Journals (Sweden)

    Jimena Sanz-Bueno

    2014-01-01

    Full Text Available We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.

  10. [Hypothyroidism Associated to TSH Hormone-Receptor Autoantibodies with Blocking Activity Assessed In Vitro].

    Science.gov (United States)

    Marques, Pedro; Chikh, Karim; Charrié, Anne; Pina, Rosa; Bugalho, Maria João; Lopes, Lurdes

    2015-01-01

    Thyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient's serum; it was estimated a 'moderate' blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis.

  11. Necrobiosis lipoidica associated with Hashimoto's thyroiditis and positive detection of ANA and ASMA autoantibodies.

    Science.gov (United States)

    Borgia, Francesco; Russo, Giuseppina T; Villari, Provvidenza; Guarneri, Fabrizio; Cucinotta, Domenico; Cannavò, Serafinella P

    2015-07-01

    Necrobiosis lipoidica (NL) is a rare idiopathic cutaneous condition exceptionally associated with autoimmune thyroiditis. We describe the first case of NL, Hashimoto's thyroiditis and positive detection of autoantibodies. Appropriate screening for NL in patients with autoimmune thyroiditis may clarify its real incidence and the existence of a common pathogenetic pathway.

  12. Autoantibodies Affect Brain Density Reduction in Nonneuropsychiatric Systemic Lupus Erythematosus Patients

    Directory of Open Access Journals (Sweden)

    Jian Xu

    2015-01-01

    Full Text Available This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE. Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD and white matter (WMD were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA, and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients.

  13. Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy.

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Laak, H.J. ter; Vree Egberts, W.T.M.; Lundberg, I.E.; Moutsopoulos, H.M.; Vencovsky, J.; Doria, A.; Mosca, M.; Venrooij, W.J.W. van; Engelen, B.G.M. van

    2006-01-01

    OBJECTIVE: To elucidate the clinical importance of the anti-signal recognition particle (SRP) autoantibody in patients with myositis. METHODS: Retrospective systematic assessment of the clinical, laboratory and histological characteristics of 23 anti-SRP-positive patients from six European centres.

  14. Autoantibodies to cytosolic 5'-nucleotidase 1A in inclusion body myositis

    NARCIS (Netherlands)

    Pluk, H.; Hoeve, B.J.A. van; Dooren, S.H. van; Stammen-Vogelzangs, J.; Heijden, A. van der; Schelhaas, H.J.; Verbeek, M.M.; Badrising, U.A.; Arnardottir, S.; Gheorghe, K.; Lundberg, I.E.; Boelens, W.C.; Engelen, B.G.M. van; Pruijn, Ger

    2013-01-01

    OBJECTIVE: Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy characterized by both degenerative and autoimmune features. In contrast to other inflammatory myopathies, myositis-specific autoantibodies had not been found in sIBM patients until recently. We used human skeletal muscle

  15. Parity and 11-Year Serum Thyrotropin and Thyroid Autoantibody Change: A Longitudinal Population-Based Study

    DEFF Research Database (Denmark)

    Bjergved, Lena; Carlé, Allan; Jørgensen, Torben

    2016-01-01

    thyrotropin (TSH), as well as change in thyroid peroxidase autoantibody (TPOAb) status. A random sample of 4649 people aged 18-65 years participated in a population-based study in the period 1997-1998. In the study presented here, 1749 non-pregnant women with no history of thyroid disease were included who...

  16. Augmentation of Autoantibodies by Helicobacter pylori in Parkinson's Disease Patients May Be Linked to Greater Severity.

    Directory of Open Access Journals (Sweden)

    Gunasekaran Suwarnalata

    Full Text Available Parkinson's disease (PD is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case and 30 age- and gender-matched H. pylori-seronegative PD patients (control in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA, Platelet-derived growth factor B (PDGFB and Eukaryotic translation initiation factor 4A3 (eIFA3. The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.

  17. Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins

    Directory of Open Access Journals (Sweden)

    Dmytro Fishman

    2017-08-01

    Full Text Available High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity.

  18. Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins

    Science.gov (United States)

    Fishman, Dmytro; Kisand, Kai; Hertel, Christina; Rothe, Mike; Remm, Anu; Pihlap, Maire; Adler, Priit; Vilo, Jaak; Peet, Aleksandr; Meloni, Antonella; Podkrajsek, Katarina Trebusak; Battelino, Tadej; Bruserud, Øyvind; Wolff, Anette S. B.; Husebye, Eystein S.; Kluger, Nicolas; Krohn, Kai; Ranki, Annamari; Peterson, Hedi; Hayday, Adrian; Peterson, Pärt

    2017-01-01

    High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity. PMID:28861084

  19. Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

    International Nuclear Information System (INIS)

    Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

    1983-01-01

    The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

  20. Autoantibodies in a Three-Year-Old Girl with Visceral Leishmaniasis: A Potential Diagnostic Pitfall

    Directory of Open Access Journals (Sweden)

    Gholamreza Pouladfar

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL, a life-threatening parasitic infection, is endemic in the Mediterranean region. Diagnosis of VL is based on epidemiologic, clinical, and laboratory findings. However, sometimes, clinical features and laboratory findings overlap with those of autoimmune diseases. In some cases, autoantibodies are detected in patients with VL and this could be a potential diagnostic pitfall. In this study, we have reported on a three-year-old girl from a VL-endemic area in Iran, who presented with prolonged fever and splenomegaly. Bone marrow examination, serologic tests, and the molecular PCR assay were performed; however, results were inconclusive. The levels of anti-double stranded DNA, cytoplasmic antineutrophil cytoplasmic autoantibody, and perinuclear antineutrophil cytoplasmic autoantibody were elevated and, at the end, splenic biopsy was performed. The splenic tissue PCR test detected the DNA of Leishmania infantum. The patient’s condition improved with anti-Leishmania therapy, and the autoantibodies disappeared within the following four months. Clinical presentations and laboratory findings of VL and autoimmune diseases may overlap in some patients.

  1. Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

    NARCIS (Netherlands)

    Sanders, J.S.F.; Huitema, M.G.; Hanemaaijer, R.; Goor, H. van; Kallenberg, C.G.M.; Stegeman, C.A.

    2007-01-01

    Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these

  2. Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher M.; Sahar, Eli

    2011-01-01

    correlation (r = 0·63, P = 0·011) between differences in IgM reactivity and differences in gene expression levels. This connection between donor lung gene expression and long‐lasting recipient IgM autoantibodies towards a specific set of proteins suggests a mechanism for the development of autoimmunity in PGD....

  3. DPD epitope-specific glutamic acid decarboxylase GAD)65 autoantibodies in children with Type 1 diabetes

    Science.gov (United States)

    To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical dat...

  4. Are pancreatic autoantibodies associated with azathioprine-induced pancreatitis in Crohn's disease?

    NARCIS (Netherlands)

    Weersma, Rinse K; Batstra, Manou R; Kleibeuker, Jan H; van Dullemen, Hendrik M

    2008-01-01

    CONTEXT: Azathioprine is frequently used in the treatment of Crohn's disease. A severe side effect is acute pancreatitis, which is specific for Crohn's disease. Autoantibodies against exocrine pancreas occur in about 30% of Crohn's disease cases but not in other inflammatory diseases. Pancreatic

  5. Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block.

    Science.gov (United States)

    Salomonsson, Stina; Sonesson, Sven-Erik; Ottosson, Lars; Muhallab, Saad; Olsson, Tomas; Sunnerhagen, Maria; Kuchroo, Vijay K; Thorén, Peter; Herlenius, Eric; Wahren-Herlenius, Marie

    2005-01-03

    Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers. The condition is often fatal and the majority of live-born children require a pacemaker at an early age. The specific antibody that induces the heart block and the mechanism by which it mediates the pathogenic effect have not been elucidated. In this study, we define the cellular mechanism leading to the disease and show that maternal autoantibodies directed to a specific epitope within the leucine zipper amino acid sequence 200-239 (p200) of the Ro52 protein correlate with prolongation of fetal atrioventricular (AV) time and heart block. This finding was further confirmed experimentally in that pups born to rats immunized with p200 peptide developed AV block. p200-specific autoantibodies cloned from patients bound cultured cardiomyocytes and severely affected Ca2+ oscillations, leading to accumulating levels and overload of intracellular Ca2+ levels with subsequent loss of contractility and ultimately apoptosis. These findings suggest that passive transfer of maternal p200 autoantibodies causes congenital heart block by dysregulating Ca2+ homeostasis and inducing death in affected cells.

  6. Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

    NARCIS (Netherlands)

    Dieker, J.W.; Berden, J.H.; Bakker, M.A.; Briand, J.P.; Muller, S.; Voll, R.; Sjowall, C.; Herrmann, M.; Hilbrands, L.B.; Vlag, J. van der

    2016-01-01

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified

  7. Thyroid peroxidase and thyroglobulin auto-antibodies in patients with newly diagnosed overt hypothyroidism

    DEFF Research Database (Denmark)

    Carle, A.; Laurberg, P.; Knudsen, N.

    2006-01-01

    Objectives: Thyroid autoimmunity is a major cause for hypothyroidism. We describe thyroid auto-antibodies in patients with various nosological subtypes of hypothyroidism identified in a population study. Design: Population-based follow-up study identifying all new cases of hypothyroidism in an open...

  8. Colostrum of Healthy Mothers Contains Broad Spectrum of Secretory IgA Autoantibodies

    Czech Academy of Sciences Publication Activity Database

    Přibylová, Jaroslava; Krausová, Klára; Kocourková, I.; Rossmann, Pavel; Klimešová, Klára; Kverka, Miloslav; Tlaskalová-Hogenová, Helena

    2012-01-01

    Roč. 32, č. 6 (2012), s. 1372-1380 ISSN 0271-9142 R&D Projects: GA ČR(CZ) GAP304/11/1252 Institutional support: RVO:61388971 Keywords : Autoantibodies * mucosal immunity * immunoglobulins Subject RIV: EC - Immunology Impact factor: 3.382, year: 2012

  9. Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven

    DEFF Research Database (Denmark)

    Schaller, Monica; Bigler, Cornelia; Danner, Doris

    2009-01-01

    Autoantibodies against complement C1q (anti-C1q Abs) were shown to strongly correlate with the occurrence of severe nephritis in patients with systemic lupus erythematosus (SLE), suggesting a potential pathogenic role by interfering with the complement cascade. To analyze the humoral immune...

  10. Quantification of HER2 autoantibodies in the amplification phenomenon of HER2 in breast cancer

    DEFF Research Database (Denmark)

    Lauterlein, Jens-Jacob L; Petersen, Eva R B; Olsen, Dorte Aa

    2011-01-01

    Gene amplification of HER2 (human epidermal growth factor receptor 2) is a well-known phenomenon in various cancers. However, little is known about the mechanism of the gene amplification phenomenon itself. Autoantibodies to cellular receptors have been described in several cancer types. We hypot...

  11. Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus.

    Science.gov (United States)

    Eriksson, C; Rantapää-Dahlqvist, S

    2014-06-01

    A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age- and sex-matched controls were also identified. The concentrations of interferon-α, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. The interferon-γ inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p lupus erythematosus. An increased concentration of interferon-γ inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-γ inducible protein-10 and interferon-α were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Pathophysiological aspects of thyroid hormone disorders/thyroid peroxidase autoantibodies and reproduction

    NARCIS (Netherlands)

    Vissenberg, R.; Manders, V. D.; Mastenbroek, S.; Fliers, E.; Afink, G. B.; Ris-Stalpers, C.; Goddijn, M.; Bisschop, P. H.

    2015-01-01

    Thyroid hormone disorders and thyroid peroxidase autoantibodies (TPO-Ab) in women are associated with subfertility and early pregnancy loss. Here, we aim to provide a comprehensive overview of the literature on the pathophysiology of these associations. A review of the literature in the English

  13. Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort

    Directory of Open Access Journals (Sweden)

    Rufei Lu

    2012-01-01

    Full Text Available Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use.

  14. Thyroid autoantibodies in autoimmune diseases Anticuerpos antitiroideos en enfermedades autoinmunes

    Directory of Open Access Journals (Sweden)

    Regina M. Innocencio

    2004-06-01

    Full Text Available Abnormalities in the thyroid function and thyroid autoantibodies have been frequently described in patients with autoimmune diseases but seldom in antiphospholipid syndrome patients. In order to determine the prevalence of thyroid function and autoimmune abnormalities, we compared serum thyrotropin (TSH, serum free thyroxine (T4 levels, thyroid antithyroglobulin (TgAb and antithyroperoxidase (TPOAb levels of 25 patients with systemic sclerosis, 25 patients with rheumatoid arthritis and 13 patients with antiphospholipid syndrome to a control group of 113 healthy individuals. Evaluation included a thorough clinical examination with particular attention to thyroid disease and a serologic immune profile including rheumatoid factor, antinuclear and anticardiolipin antibody measurements. Subclinical hypothyroidism (4.2Ciertas anormalidades en la función tiroidea y anticuerpos antitiroideos han sido frecuentemente descriptos en pacientes con enfermedades autoinmunes, y más raramente en pacientes con el síndrome antifosfolipídico. Para determinar la prevalencía de anormalidades en la función tiroidea y de autoinmunidad, comparamos los niveles séricos de tirotropina (TSH tiroxina libre en suero (T4 anticuerpos antitiroglobulina (TgAb y antitiroperoxidasa (TPOAb en 25 pacientes con esclerosis sistémica, 25 pacientes con artritis reumatoidea y 13 pacientes con el síndrome antifosfolipídico con un grupo control de 113 individuos aparentemente sanos. La evaluación incluyó un completo examen clínico con particular atención para las enfermedades de la tiroides y una evaluación inmunológica incluyendo dosaje del factor reumatoideo, anticuerpos antinucleares y anticardiolipina. Hipotiroidismo subclínico (4.2

  15. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

    Directory of Open Access Journals (Sweden)

    Sandra M. McLachlan

    2017-12-01

    Full Text Available Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg, thyroid peroxidase (TPO, and the thyrotropin receptor (TSHR A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of spontaneously arising pathogenic TSHR antibodies in transgenic human thyrotropin receptor/NOD.H2h4 mice by injecting a non-pathogenic form of TSHR A-subunit protein also provides evidence for original antigenic sin. From other studies, antigen presentation by B cells, not dendritic cells, is likely responsible for original antigenic sin. Recognition of restricted epitopes on the large glycosylated thyroid autoantigens (60-kDa A-subunit, 100-kDa TPO, and 600-kDa Tg facilitates exploring the amino acid locations in the immunodominant regions. Epitope spreading has also been revealed by autoantibodies in thyroid autoimmunity. In humans, and in mice that spontaneously develop autoimmunity to all three thyroid autoantigens, autoantibodies develop first to Tg and later to TPO and the TSHR A-subunit. The pattern of intermolecular epitope spreading is related in part to the thyroidal content of Tg, TPO and TSHR A-subunit and to the molecular sizes of these proteins. Importantly, the epitope spreading pattern provides a rationale for future antigen-specific manipulation to block the development of all thyroid autoantibodies by inducing tolerance to Tg, first in the autoantigen cascade. Because of its abundance, Tg may be the autoantigen of choice to explore antigen-specific treatment, preventing the development of pathogenic TSHR antibodies.

  16. AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED.

    Science.gov (United States)

    Cervato, Sara; Morlin, Luca; Albergoni, Maria Paola; Masiero, Stefano; Greggio, Nella; Meossi, Cristiano; Chen, Shu; del Pilar Larosa, Maria; Furmaniak, Jadwiga; Rees Smith, Bernard; Alimohammadi, Mohammad; Kämpe, Olle; Valenzise, Mariella; Betterle, Corrado

    2010-11-01

    To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ- or non-organ-specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison's disease (AD) or chronic candidiasis (CC). Twenty-four patients who had CH without AD or CC were included in the study. AIRE gene mutations in all 14 exons were studied using PCR in 24 patients, 105 healthy controls and 15 first-degree relatives of CH patients with AIRE mutations. Human leucocyte antigens (HLA) were determined for all 24 patients and 105 healthy controls. Autoantibodies to a range of antigens including NACHT leucine-rich-repeat protein-5 (NALP5) and interferon omega (IFNω) were tested in all 24 patients. AIRE gene mutations were found in 6 of 24 (25%) patients, all females, and this was significantly higher (P < 0·001) compared with AIRE mutations found in healthy controls (2/105). Three patients (12·5%) had homozygous AIRE mutations characteristic of Autoimmune-Poly-Endocrinopathy-Candidiasis-Ectodermal-Dystrophy and all three were also positive for IFNω-autoantibodies. Three patients (12·5%) had heterozygous AIRE mutations; two of these were novel mutations. One of the patients with heterozygous AIRE mutations was positive for both NACHT leucine-rich-repeat protein 5 and IFNω autoantibodies. Heterozygous AIRE mutations were found in 10 of 15 first-degree relatives of CH patients with AIRE mutations, although none was affected by CH. Class II HLA haplotypes were not statistically different in patients with CH compared to healthy controls. Analysis of AIRE gene mutations together with serum autoantibody profile should be helpful in the assessment of patients with CH, in particular young women with associated autoimmune diseases. © 2010 Blackwell Publishing Ltd.

  17. Tumor-associated autoantibody signature for the early detection of gastric cancer.

    Science.gov (United States)

    Zayakin, Pawel; Ancāns, Guntis; Siliņa, Karīna; Meistere, Irēna; Kalniņa, Zane; Andrejeva, Diāna; Endzeliņš, Edgars; Ivanova, Lāsma; Pismennaja, Angelina; Ruskule, Agnese; Doniņa, Simona; Wex, Thomas; Malfertheiner, Peter; Leja, Mārcis; Linē, Aija

    2013-01-01

    Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150-feature microarray was tested with sera from 100 patients with GC and 100 cancer-free controls, and then the top-ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45-autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease. Copyright © 2012 UICC.

  18. Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies

    Science.gov (United States)

    Wiberg, A; Granstam, A; Ingvast, S; Härkönen, T; Knip, M; Korsgren, O; Skog, O

    2015-01-01

    In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3·3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52·6 (range 21–74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases. PMID:26313035

  19. Characterization of a cDNA encoding a 34-kDa Purkinje neuron protein recognized by sera from patients with paraneoplastic cerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Furneaux, H.M.; Dropcho, E.J.; Barbut, D.; Chen, Yaotseng; Rosenblum, M.K.; Old, L.J.; Posner, J.B. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

    1989-04-01

    Paraneoplastic cerebellar degeneration is a neurological disorder of unknown cause occurring in patients with an identified or occult cancer. An autoimmune etiology is likely since autoantibodies directed against the Purkinje cells of the cerebellum have been found in the serum and cerebrospinal fluid of some patients. Two Purkinje cell-specific antigens are recognized by these autoantibodies, a major antigen of 62 kDa (CDR 62, cerebellar degeneration-related 62-kDa protein) and a minor antigen of 34 kDa (CDR 34). Previous studies have described the isolation and characterization of a human cerebellar cDNA that encodes an epitope recognized by sera from patients with paraneoplastic cerebellar degeneration. The authors have now established by two independent methods that this gene is uniquely expressed in Purkinje cells of the cerebellum and corresponds to the minor antigen CDR 34. This antigen is also expressed in tumor tissue from a patient with paraneoplastic cerebellar degeneration.

  20. The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Choi, M. Y.; Clarke, A. E.; St Pierre, Y.

    2017-01-01

    , clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate......Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic...

  1. Peptide Signals Encode Protein Localization▿

    OpenAIRE

    Russell, Jay H.; Keiler, Kenneth C.

    2007-01-01

    Many bacterial proteins are localized to precise intracellular locations, but in most cases the mechanism for encoding localization information is not known. Screening libraries of peptides fused to green fluorescent protein identified sequences that directed the protein to helical structures or to midcell. These peptides indicate that protein localization can be encoded in 20-amino-acid peptides instead of complex protein-protein interactions and raise the possibility that the location of a ...

  2. IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice.

    Directory of Open Access Journals (Sweden)

    Yuriy Baglaenko

    Full Text Available The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations.

  3. IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice.

    Science.gov (United States)

    Baglaenko, Yuriy; Manion, Kieran P; Chang, Nan-Hua; Gracey, Eric; Loh, Christina; Wither, Joan E

    2016-01-01

    The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations.

  4. Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes.

    Science.gov (United States)

    Quintana, Francisco J; Hagedorn, Peter H; Elizur, Gad; Merbl, Yifat; Domany, Eytan; Cohen, Irun R

    2004-10-05

    One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune disease? Here, we developed an antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes developing in nonobese diabetic male mice in which the disease was accelerated and synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained sera from 19 individual mice, treated the mice to induce cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9 mice became severely diabetic, whereas 10 mice permanently resisted diabetes. We again obtained serum from each mouse after CAD induction. We then analyzed, by using rank-order and superparamagnetic clustering, the patterns of antibodies in individual mice to 266 different antigens spotted on the chip. A selected panel of 27 different antigens (10% of the array) revealed a pattern of IgG antibody reactivity in the pre-CAD sera that discriminated between the mice resistant or susceptible to CAD with 100% sensitivity and 82% specificity (P = 0.017). Surprisingly, the set of IgG antibodies that was informative before CAD induction did not separate the resistant and susceptible groups after the onset of CAD; new antigens became critical for post-CAD repertoire discrimination. Thus, at least for a model disease, present antibody repertoires can predict future disease, predictive and diagnostic repertoires can differ, and decisive information about immune system behavior can be mined by bioinformatic technology. Repertoires matter.

  5. Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases.

    Directory of Open Access Journals (Sweden)

    Guo Luo

    Full Text Available A recent publication suggested molecular mimicry of a nucleoprotein (NP sequence from A/Puerto Rico/8/1934 (PR8 strain, the backbone used in the construction of the reassortant strain X-179A that was used in Pandemrix® vaccine, and reported on anti-hypocretin (HCRT receptor 2 (anti-HCRTR2 autoantibodies in narcolepsy, mostly in post Pandemrix® narcolepsy cases (17 of 20 sera. In this study, we re-examined this hypothesis through mass spectrometry (MS characterization of Pandemrix®, and two other pandemic H1N1 (pH1N1-2009 vaccines, Arepanrix® and Focetria®, and analyzed anti-HCRTR2 autoantibodies in narcolepsy patients and controls using three independent strategies.MS characterization of Pandemrix® (2 batches, Arepanrix® (4 batches and Focetria® (1 batch was conducted with mapping of NP 116I or 116M spectrogram. Two sets of narcolepsy cases and controls were used: 40 post Pandemrix® narcolepsy (PP-N cases and 18 age-matched post Pandemrix® controls (PP-C, and 48 recent (≤6 months early onset narcolepsy (EO-N cases and 70 age-matched other controls (O-C. Anti-HCRTR2 autoantibodies were detected using three strategies: (1 Human embryonic kidney (HEK 293T cells with transient expression of HCRTR2 were stained with human sera and then analyzed by flow cytometer; (2 In vitro translation of [35S]-radiolabelled HCRTR2 was incubated with human sera and immune complexes of autoantibody and [35S]-radiolabelled HCRTR2 were quantified using a radioligand-binding assay; (3 Optical density (OD at 450 nm (OD450 of human serum immunoglobulin G (IgG binding to HCRTR2 stably expressed in Chinese hamster ovary (CHO-K1 cell line was measured using an in-cell enzyme-linked immunosorbent assay (ELISA.NP 116M mutations were predominantly present in all batches of Pandemrix®, Arepanrix® and Focetria®. The wild-type NP109-123 (ILYDKEEIRRIWRQA, a mimic to HCRTR234-45 (YDDEEFLRYLWR, was not found to bind to DQ0602. Three or four subjects were found positive

  6. Thyroid profile and autoantibodies in Type 1 diabetes subjects: A perspective from Eastern India

    Directory of Open Access Journals (Sweden)

    Debmalya Sanyal

    2017-01-01

    Full Text Available Context: There has been a rise in the incidence of type 1 diabetes mellitus (T1DM in India. The prevalence of thyroid autoantibodies and thyroid dysfunction is common in T1DM. Aims: The aim of this study is to determine the incidence of thyroid dysfunction and thyroid autoantibodies in T1DM subjects, without any history of thyroid disease, and the prevalence of glutamic acid decarboxylase (GAD antibody, Islet antigen-2 antibody (IA2, thyroid peroxidase (TPO, and thyroglobulin autoantibodies (Tg-AB in T1DM subjects. Settings and Design: This was a cross-sectional clinical-based study. Subjects and Methods: Fifty subjects (29 males, 31 females with T1DM and without any history of thyroid dysfunction were included in the study. All subjects were tested for GAD antibody, IA2 antibody, TPO antibody, thyroglobulin antibody, free thyroxine, and thyroid-stimulating hormone. Statistical Analysis Used: A Chi-square/pooled Chi-square test was used to assess the trends in the prevalence of hypothyroidism. A two-tailed P< 0.05 was considered statistically significant. Results: The mean age of the subjects was 23.50 years. 9.8% of subjects were below the age of 12 years, 27.45% of subjects were of age 12–18 years, 37.25% of subjects were of age 19–30 years, and 25.49% of subjects were above 30 years. 78% were positive autoantibody for GAD, 30% for IA-2, 24% for TPO, and 16% were positive for Tg-AB. A total of 6.0% of T1DM subjects had evidence of clinical hypothyroidism, but the prevalence of subclinical hyperthyroidism (SCH varied from 32% to 68.0% for we considered different definitions of SCH as advocated by different guidelines. All subjects with overt hypothyroidism had positive GAD and thyroid autoantibodies. One (2% subject had clinical hyperthyroidism with strongly positive GAD, TPO, and Tg-AB. Conclusions: We found a high prevalence of GAD, IA2, TPO, and Tg-AB in our T1DM subjects. A substantial proportion of our subjects had undiagnosed thyroid

  7. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice.

    NARCIS (Netherlands)

    Klooster, R.; Plomp, J.J.; Huijbers, M.G.; Niks, E.H.; Straasheijm, K.R.; Detmers, F.J.M.; Hermans, P.W.M.; Sleijpen, K.; Verrips, A.; Losen, M.; Martinez-Martinez, P.; Baets, M.H.V. de; Maarel, S.M. van der; Verschuuren, J.J.

    2012-01-01

    Myasthenia gravis is a paralytic disorder with autoantibodies against acetylcholine receptors at the neuromuscular junction. A proportion of patients instead has antibodies against muscle-specific kinase, a protein essential for acetylcholine receptor clustering. These are generally of the

  8. Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY).

    Science.gov (United States)

    Steck, Andrea K; Vehik, Kendra; Bonifacio, Ezio; Lernmark, Ake; Ziegler, Anette-G; Hagopian, William A; She, JinXiong; Simell, Olli; Akolkar, Beena; Krischer, Jeffrey; Schatz, Desmond; Rewers, Marian J

    2015-05-01

    While it is known that there is progression to diabetes in IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months. Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma.

    Science.gov (United States)

    Peng, Yu-Hui; Xu, Yi-Wei; Qiu, Si-Qi; Hong, Chao-Qun; Zhai, Tian-Tian; Li, En-Min; Xu, Li-Yan

    2014-09-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

  10. Anti-rods and rings autoantibodies can occur in the hepatitis c-naïve population.

    Science.gov (United States)

    Shaikh, Y; Krantz, A; El-Farra, Y

    2013-09-01

    The anti-Rods and Rings autoantibody recently described in clinical populations is thought to occur in the setting of hepatitis C treatment, specifically in the context of cytidine triphosphate (CTP) and guanosine triphosphate (GTP) synthetic pathway inhibitors, and is important in its potential impact on response to therapy. This study asks the question: what is the epidemiology of anti-RR autoantibody in the general, non-clinical population? This is a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES). Immunofluorescence assay for anti-Rods and Rings autoantibody were performed by NHANES labs and the results made publically available. Sample weights were used to calculate the prevalence and distribution of the autoantibody across demographics. A medication profile of the autoantibody positive population was also constructed The study sample consisted of 4738 persons over the age of 12 years. Anti-Rods and Rings autoantibodies were found in 39 persons representing 1.3 million persons in the United States population. 38 of 39 persons with anti-Rods and Rings autoantibody had no prior history of hepatitis C virus infection. A majority of these persons were found to have poly-pharmacy. This is the first study to show that anti-RR can occur in the general population without evidence of hepatits C virus infection, and that the majority of persons with anti-RR in the population have no evidence of prior hepatitis C infection. This indicates that there may be another undetermined etiology for anti-rods and rings autoantibodies besides the currently accepted exposure etiology of hepatitis C virus infection and treatment found in clinical studies.

  11. Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3-6 years

    DEFF Research Database (Denmark)

    Sørensen, Jesper Sand; Vaziri-Sani, Fariba; Maziarz, M

    2012-01-01

    To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D.......To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D....

  12. Comparison of the prevalence of islet autoantibodies according to age and disease duration in patients with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Young Hwa Kong

    2013-06-01

    Full Text Available PurposeThis study investigated the prevalence of islet autoantibodies in children and adults with T1DM according to their age and the duration of disease.MethodsWe measured the levels of islet autoantibodies, including antiglutamic acid decarboxylase antibody (anti-GAD Ab, and combined these with anthropometric measurements and laboratory tests of 137 patients newly diagnosed with T1DM during the last 20 years. The subjects were subdivided into four groups according to their age at the onset of the disease. We then compared the prevalence of islet autoantibodies in the different age groups with the duration of disease.ResultsAmong the 137 patients, 68.9% tested positive for islet autoantibodies (71.4% within 1 year; 67.7% after 1 year of the disease onset. Within 1 year of the onset of the disease, 66.3% of the patients were positive for the anti-GAD Ab, and 35.6% were positive for IAAs. The prevalence of islet autoantibodies was significantly higher in the prepubertal groups than in the postpubertal groups (80.0% vs. 58.3%. The rate of positive islet autoantibodies changed with the duration of disease, and it differed according to the type of autoantibody and the age of the patient.ConclusionThe rates of positive islet autoantibodies were significantly higher in younger than in older patients at the time of the diagnosis of the disease. The positive rates were significantly changed 1 year after the onset of the disease in the preschool and the children groups. So these findings suggest that we need to diagnose type 1B diabetes distinguished T2DM in aldolescent group, carefully.

  13. Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

    Science.gov (United States)

    Yuan, Mo; Tan, Ying; Pang, Yun; Li, Yong-Zhe; Song, Yan; Yu, Feng; Zhao, Ming-Hui

    2017-11-01

    Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

  14. Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non ovarian cancer with various CA-125 levels

    Science.gov (United States)

    Karabudak, Aykan; Hafner, Julie; Shetty, Vivekananda; Chen, Songming; Secord, Angeles Alvarez; Morse, Michael

    2013-01-01

    Purpose CA-125 has been a valuable marker for detecting ovarian cancer, however, not sensitive enough to detect early stage disease and not specific for ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific for ovarian cancer regardless of CA-125 levels. Methods Top-down and iTRAQ quantitative proteomics methods were used to identify high frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers. Results The proteomics methodologies identified >60 potential high frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels. Conclusions Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant for early detection of ovarian cancer. PMID:23999876

  15. Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

    Science.gov (United States)

    Karabudak, Aykan A; Hafner, Julie; Shetty, Vivekananda; Chen, Songming; Secord, Angeles Alvarez; Morse, Michael A; Philip, Ramila

    2013-10-01

    CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels. Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers. The proteomics methodologies identified more than 60 potential high-frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high-frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels. Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant to early detection of ovarian cancer.

  16. Multidimensionally encoded magnetic resonance imaging.

    Science.gov (United States)

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

  17. Restriction in the repertoire of detectable autoantibodies in polyclonal B cell activations and the mimicry of autoantigens by idiotopes

    Directory of Open Access Journals (Sweden)

    L. C. Pontes de Carvalho

    1987-01-01

    Full Text Available Despite the existence of erythrocyte-autoreactive B cells in normal animals, erythrocyte-autoantibodies could not be detected during polyclonal B-cell activation (PBA both in patients with visceral leishmaniasis and in bacterial lipopolysacharide (LPS - injected mice. The failure to detect these autoantibodies in mice with PBA di not seem to be due to suppressor-cell activity, since (1 transfer of spleen cells from LPS-treated mice to naive recipients did not affect the erythrocyte-autoantibody response elicited by subsequent injections of rat erythrocytes and (2 low doses of X-radiation did no lead to erythrocyte-autoantibody detection in LPS-treated mice. The possibility that the detection of erytrocyte-autoantibodies could be affected by autoantibodies with idiotopes mimicring erythrocyte epitopes, the synthesis of which would also be triggerred in PBA, is discussed. Indirect evidence for the existence in normal animal of an expanded lymphocyte population with DNP-binding. Ia-mimicring antigen receptors is presented.

  18. Radioimmunoassays for glutamic acid decarboxylase (GAD65) and GAD65 autoantibodies using 35S or 3H recombinant human ligands.

    Science.gov (United States)

    Falorni, A; Ortqvist, E; Persson, B; Lernmark, A

    1995-10-12

    Autoantibodies are an important marker of human autoimmune diseases and the development of simple, precise and reproducible immunoassays to detect autoantibodies is important to our understanding of human autoimmunity. GAD65 autoantibodies occur frequently in insulin-dependent diabetic patients and is a useful marker for IDDM. A RIA to detect immunoreactive GAD65 has not been described. In the present study we describe a semi-automated fluid-phase immunoassay for the rapid detection of GAD65 autoantibodies in human serum. We also developed a sensitive RIA to determine immunoreactive human GAD65 in biological fluids and in vitro cell systems. Using in vitro translated recombinant human GAD65 in a multiwell-adapted procedure, our GAD65Ab RIA combines high specificity and sensitivity with a high capacity to analyze a large number of samples. In this report the three critical steps in the GAD65Ab RIA, DNA preparation, in vitro translation and immunoprecipitation, have been optimized. In our RIA, GAD65Ab were detected in 116/155 (75%) new onset Swedish IDDM children and in 1/85 (1.2%) healthy controls. In an immunoassay to detect autoantibodies against the proinsulin converting enzyme 2 (PC-2) no such antibodies were detected in IDDM patients. In the GAD65 RIA the lower detection limit was 2 ng/ml (31 fmol/ml). Our data demonstrate that autoantigen radioligands produced by in vitro translation are useful in RIA for autoantibodies and autoantigens in studies of human autoimmunity.

  19. Autoantibodies to neurotransmitter receptors and ion channels: from neuromuscular to neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Pilar eMartinez-Martinez

    2013-09-01

    Full Text Available Changes of voltage-gated ion channels and ligand-gated receptor channels caused by mutation or autoimmune attack are the cause of so-called channelopathies in the central and peripheral nervous system. We present the pathophysiology of channelopathies of the neuromuscular junction in terms of loss-of-function and gain-of-function principles. Autoantibodies generally have reduced access to the CNS, but in some cases this is enough to cause disease. A review is provided of recent findings implicating autoantibodies against ligand–activated receptor channels and potassium channels in psychiatric and neurological disorders, including schizophrenia and limbic encephalitis. The emergence of channelopathy-related neuropsychiatric disorders has implications for research and practice.

  20. Anti-neutrophil cytoplasm autoantibodies (ANCA). The need for specific and sensitive assays

    DEFF Research Database (Denmark)

    Baslund, B; Petersen, J

    1998-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are a group of autoantibodies primarily associated with systemic vasculitis. Hitherto, the method of choice for ANCA detection has been indirect immunofluorescence (IIF). By this method two major patterns can be seen: a cytoplasmic pattern (cANCA) or a ......Anti-neutrophil cytoplasm antibodies (ANCA) are a group of autoantibodies primarily associated with systemic vasculitis. Hitherto, the method of choice for ANCA detection has been indirect immunofluorescence (IIF). By this method two major patterns can be seen: a cytoplasmic pattern (c......ANCA) or a perinuclear pattern (pANCA). The cANCA pattern is most often caused by antibodies directed against proteinase-3 (PR3) and in rare cases it is caused by anti-myeloperoixdase (MPO) antibodies. The pANCA pattern can de caused by antibodies directed against a large group of proteins i.e. MPO, lactofenin...

  1. Misfolded proteins complexed with MHC class II molecules are targets for autoantibodies.

    Science.gov (United States)

    Hiwa, Ryosuke; Arase, Hisashi

    2016-01-01

    Major histocompatibility complex (MHC) molecule is important for immune system through its function of presentation of peptide antigens. MHC is the gene most strongly associated with susceptibility to many autoimmune diseases. We recently found a novel function of MHC class II molecules to transport cellular misfolded proteins to the cell surface without processing to peptides. Interestingly, misfolded proteins transported to the cell surface by MHC class II molecules were found to be a specific targets for autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is strongly associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins associated with MHC class II molecules might be involved in the pathogenesis of autoimmune diseases.

  2. Autoantibodies to folate receptor alpha during early pregnancy and risk of oral clefts in Denmark

    DEFF Research Database (Denmark)

    Bille, Camilla; Pedersen, Dorthe Almind; Andersen, Anne-Marie Nybo

    2010-01-01

    The objective of this study was to determine whether IgG and IgM autoantibodies to folate receptor alpha (FRalpha) in pregnant women are associated with an increased risk of oral cleft-affected offspring. A case-control study nested in the prospective Danish National Birth Cohort (100......,418 pregnancies, enrolled during 1997-2003) was done. Hundred eighty-five children were born with an oral cleft. Maternal serum from their mothers (cases) was compared with maternal serum from 779 randomly selected mothers of nonmalformed children (controls). We found that the average level of FRalpha Ig.......04). Blocking of folate binding to FR was similar among cases and controls (p = 0.54). The results did not change when stratifying into the cleft subgroups, nor when only isolated oral cleft cases were considered. In conclusion, high maternal autoantibody levels and blocking of folate binding to FRalpha...

  3. Synthetic Peptide-Based ELISA and ELISpot Assay for Identifying Autoantibody Epitopes.

    Science.gov (United States)

    Pozsgay, Judit; Szarka, Eszter; Huber, Krisztina; Babos, Fruzsina; Magyar, Anna; Hudecz, Ferenc; Sarmay, Gabriella

    2016-01-01

    Enzyme-linked immunosorbent assay (ELISA) is an invaluable diagnostic tool to detect serum autoantibody binding to target antigen. To map the autoantigenic epitope(s), overlapping synthetic peptides covering the total sequence of a protein antigen are used. A large set of peptides synthesized on the crown of pins can be tested by Multipin ELISA for fast screening. Next, to validate the results, the candidate epitope peptides are resynthesized by solid-phase synthesis, coupled to ELISA plate directly, or in a biotinylated form, bound to neutravidin-coated surface and the binding of autoantibodies from patients' sera is tested by indirect ELISA. Further, selected epitope peptides can be applied in enzyme-linked immunospot assay to distinguish individual, citrullinated peptide-specific autoreactive B cells in a pre-stimulated culture of patients' lymphocytes.

  4. Autoantibodies and Resident Renal Cells in the Pathogenesis of Lupus Nephritis: Getting to Know the Unknown

    Directory of Open Access Journals (Sweden)

    Susan Yung

    2012-01-01

    Full Text Available Systemic lupus erythematosus is characterized by a breakdown of self-tolerance and production of autoantibodies. Kidney involvement (i.e., lupus nephritis is both common and severe and can result in permanent damage within the glomerular, vascular, and tubulo-interstitial compartments of the kidney, leading to acute or chronic renal failure. Accumulating evidence shows that anti-dsDNA antibodies play a critical role in the pathogenesis of lupus nephritis through their binding to cell surface proteins of resident kidney cells, thereby triggering the downstream activation of signaling pathways and the release of mediators of inflammation and fibrosis. This paper describes the mechanisms through which autoantibodies interact with resident renal cells and how this interaction plays a part in disease pathogenesis that ultimately leads to structural and functional alterations in lupus nephritis.

  5. Prognostic relevance of Bmi-1 expression and autoantibodies in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Liu, Wan-li; Li, Man-zhi; Song, Li-bing; Zeng, Mu-sheng; Guo, Xian-zhi; Zhang, Lan-jun; Wang, Jun-ye; Zhang, Ge; Guan, Su; Chen, Yu-min; Kong, Qing-li; Xu, Li-hua

    2010-01-01

    Overexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients. The objective of this study was to determine the level of Bmi-1 expression or its autoantibodies in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic data. We first examined Bmi-1 expression in ESCC cell lines and tumor samples by RT-PCR and Western blot analysis. We then analyzed Bmi-1 protein expression in 171 clinicopathologically characterized ESCC cases by immunohistochemistry. In addition, we detected its autoantibodies in sera of patients with ESCC by ELISA. We found that Bmi-1 expression was higher in the immortalized cells, cancer cell lines and most cancer tissue than in non-tumorous control tissue at both mRNA and protein level. In addition, Bmi-1 expression was observed in 64.3% (110 of 171) archive ESCC specimen by immunohistochemistry analysis, and the location of Bmi-1 in ESCC was in the nuclei instead of cytoplasm of tumor cells. There was a significant difference of Bmi-1 expression in patients categorized according to stage (P = 0.003) and pN classification (P = 0.047). Multivariate analysis suggested that Bmi-1 expression was an independent prognostic marker for ESCC patients. A prognostic significance of Bmi-1 was also found in the subgroup of T3~T4 and N1 tumor classification. Bmi-1 autoantibodies were detected in sera of 39.0% (62 of 159) ESCC patients. The correlations between anti-Bmi-1 antibodies and tumor stage (P = 0.040), or lymph node status (P < 0.001) were significant. Our results suggest that Bmi-1 protein is a valuable marker of ESCC progression. The presence of Bmi-1 autoantibodies in sera from patients with ESCC may have clinical utility in esophageal cancer diagnosis

  6. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinat...

  7. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    IL-6 is involved in inflammation and a therapeutic target. 0.1% of Danish blood donors have nanomolar plasma concentrations of polyclonal, picomolar affinity and in vitro as well as in vivo neutralizing IgG autoantibodies to IL-6 (aAb-IL-6). Such donors are assumed to be severely IL-6 deficient; ...... principle might be a viable alternative in immune competent humans suffering from disorders driven by IL-6....

  8. The Analysis of the Value of the Thyroid Autoantibody Measured by Radioimmunoassay

    International Nuclear Information System (INIS)

    Chung, Jae Hoon; Lee, Myung Shik; Cho, Bo Youn; Lee, Hong Kyu; Koh, Chang Soon; Min, Hun Ki; Lee, Mun Ho

    1987-01-01

    To evaluate the values of the thyroid autoantibody measured by radioimmunoassay (RIA) and compare it with hemagglutination method (HA) in the normal and the thyroid disease, data were obtained from total 618 persons; 236 healthy persons, 217 patients with Graves disease (including 113 patients with undertreated Graves' disease), 100 Hashimoto's disease, 31 thyroid nodule, and 34 simple goiter. RSR kit made in England was used and could be detected at least 3 U/ml. The positive rates of normal group were antirnicrosomal antibody (AMA) 31.8%, antithyroglobulin antibody (ATA) 44.5% by RIA and there was no considerable change in sex and age distribution. In Graves disease, the positive rates of AMA and ATA were 90.4, 76.9% by RIA, 85, 39% by HA. In Hashimoto's disease, 94,91% by RIA, and 87,48% by HA, respectively. The autoantibody titer by RIA in thyroid autoimmune disease as welt as in normal group was more sensitive than that by HA, especially in ATA. There were linear relationships between the titer of RIA and that of HA in AMA of Graves disease and AMA and ATA of Hashimotos disease. There was no relationship among thyroid autoantibody, free T, index, TBII, and TSH. The titers of AMA and ATA were found to decrease in patients with Graves disease during the course of antithyroid drug therapy. Of the 236 normal subjects, thirty-seven (15.7%) had concentrations of above 7.5 U/ml in AMA, forty-four (18. 6%) above 9 U/ml in ATA. These values were considered as the upper limit for the normal range. In Graves disease, 82,7, 53.8% were above 7.5, 9 U/ml, respectively; In Hashimoto's disease, HZ, 79% were positive. We conclude that RIA was more sensitive than HA in measuring the thyroid autoantibody, but we will study further more for determining the normal range and its interpretation.

  9. Chronic malaria revealed by a new fluorescence pattern on the antinuclear autoantibodies test.

    Directory of Open Access Journals (Sweden)

    Benjamin Hommel

    Full Text Available BACKGROUND: Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA. METHODS: We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. RESULTS: We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. CONCLUSION: In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy.

  10. The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

    DEFF Research Database (Denmark)

    Liszewski, Walter; Gniadecki, Robert

    2016-01-01

    Cytokines are small, secreted proteins that are essential for promoting and maintaining a normal immune response. Upregulation of cytokines frequently occurs in autoimmune and inflammatory diseases. Conversely, several immunodeficiency, autoimmune and autoinflammatory disorders are known to occur...... review the role of cytokine deficiencies and cytokine autoantibodies in immunodeficiency syndromes, as well as in autoimmune disorders. Finally, we will examine autoinflammatory disorders due to cytokine deficiencies....

  11. Automated Indirect Immunofluorescence Evaluation of Antinuclear Autoantibodies on HEp-2 Cells

    OpenAIRE

    Voigt, Jörn; Krause, Christopher; Rohwäder, Edda; Saschenbrecker, Sandra; Hahn, Melanie; Danckwardt, Maick; Feirer, Christian; Ens, Konstantin; Fechner, Kai; Barth, Erhardt; Martinetz, Thomas; Stöcker, Winfried

    2012-01-01

    Indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells is considered as the gold standard screening method for the detection of antinuclear autoantibodies (ANA). However, in terms of automation and standardization, it has not been able to keep pace with most other analytical techniques used in diagnostic laboratories. Although there are already some automation solutions for IIF incubation in the market, the automation of result evaluation is still in its infancy. Therefore, the E...

  12. Proteomics Approaches to Identify Tumor Antigen Directed Autoantibodies as Cancer Biomarkers

    OpenAIRE

    Imafuku, Yuji; Omenn, Gilbert S.; Hanash, Samir

    2004-01-01

    The identification of autoantibodies to tumor cell proteins by proteomics approaches has great potential impact on cancer biomarker discovery. The humoral immune response represents a form of biological amplification of signals that are otherwise weak due to very low concentrations of antigen, especially in the early stages of cancers. In addition, proteomics can detect immunoreactivity directed against protein post-translational modifications. Two-dimensional gel based Western blots, protein...

  13. Autoantibody profiling of patients with antiphospholipid syndrome using an automated multiplexed immunoassay system.

    Science.gov (United States)

    Tozzoli, R; Villalta, D

    2014-01-01

    The antiphospholipid syndrome (APS) is an autoimmune disease defined by the co-occurrence of clinical and serological symptoms [presence of at least one of the antiphospholipid autoantibodies (aPL), such as anti-cardiolipin (aCL) IgG/IgM and anti-β2glycoprotein I (aβ2GPI) IgG/IgM]. The measurement of these autoantibodies constitutes the first-line approach for the diagnosis of APS. Recently the advent of multiplex proteomic technologies seems to be an optimal solution for the parallel detection of autoantibodies (IgG, IgA, IgM) related to APS. The BioPlex 2200 is an automated commercial platform based on the multi-analyte profiling technology that allows the detection of different types of autoantibodies, particularly ANA, ENA, dsDNA, PR3, MPO, GBM. We performed firstly a study to evaluate the diagnostic accuracy of this analytical system in a group of APS patients. The BioPlex system showed a good diagnostic accuracy for all test evaluated, very similar to that of the other established commercial singleplex immunoassays. In our study, the simultaneous detection of aCL and aβ2GPI of IgA isotype in addition to IgG and IgM isotypes did not increase the diagnostic sensitivity for APS. The good diagnostic accuracy, the high level of automation, and the high throughput make this multiplex platform a very useful and practical tool for the laboratory diagnosis of aPL in daily practice. © 2013 Elsevier B.V. All rights reserved.

  14. Paving the way to understand humoral autoantibody epilepsy on the molecular level

    Directory of Open Access Journals (Sweden)

    Guiscard eSeebohm

    2015-07-01

    Full Text Available Correct function of neuronal networks is enabled by a delicate interplay among neurons communicating with each other. One of the keys is the communication at chemical synapses where neurotransmitters like glutamate, GABA and glycine enable signal transfer over the synaptic cleft. Thereby, the neurotransmitters are released from the presynapse and bind as ligands to specific receptors at the postsynaptic side to allow for modulation of the postsynaptic membrane potentials. The postsynaptic electrical signal, which is highly modulated by voltage gated ion channels, spreads over the dendritic tree and is thus integrated to allow for generation of action potentials at the axon hillock. This concert of receptors and voltage gated ion channels depends on correct function of all its components. Misfunction of receptors and/or voltage-gated potassium channels (VGKC leads to diverse adverse effects in patients. Such malfunctions can be the result of inherited genetic alterations or pharmacological side effects by drugs. Recently, auto-antibodies targeting receptor or channel complexes like NMDAR, AMPAR, GABA-receptors, glycine-receptors, LGI1 or CASPR2 (previously termed VGKC-complex antibodies have been discovered. The presence of specific auto-antibodies against these targets associates with severe forms of antibody-mediated encephalitis. Understanding the molecular details of auto-antibody actions on receptor and VGKC complexes is highly desirable and may open the path to develop specific therapies to treat humoral autoimmune encephalitis. Here, we summarize the current knowledge and discuss technical approaches to fill the gap of knowledge. These techniques include electrophysiology, biochemical approaches for epitope mapping and in silico modeling to simulate molecular interactions between autoantibody and its molecular target.

  15. Novel Autoantibody Serum and Cerebrospinal Fluid Biomarkers in Veterans with Gulf War Illness

    Science.gov (United States)

    2017-10-01

    applicable Other: -- The DUHS IRB has determined the specific components above to be in compliance with all applicable Health Insurance ... health of veterans with GWI is not improving. Such blood-based autoantibodies may prove useful as biomarkers of GWI, upon validation of the findings using...of the project? o The major goals of the project as stated in the approved SOW are listed in the table below. Milestones/target dates for important

  16. Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice

    Science.gov (United States)

    Kärner, J.; Meager, A.; Laan, M.; Maslovskaja, J.; Pihlap, M.; Remm, A.; Juronen, E.; Wolff, A. S. B.; Husebye, E. S.; Podkrajšek, K. T.; Bratanic, N.; Battelino, T.; Willcox, N.; Peterson, P.; Kisand, K.

    2013-01-01

    Summary Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions they neutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE. Moreover, autoantibodies against Th17 cell-associated cytokines correlate with chronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsible for neutralizing IFN-ω, IFN-α2a, interleukin (IL)-17A and IL-22. Their dominant subclasses proved to be IgG1 and, surprisingly, IgG4 without IgE, possibly implicating regulatory T cell responses and/or epithelia in their initiation in these AIRE-deficiency states. The epitopes on IL-22 and IFN-α2a appeared mainly conformational. We also found mainly IgG1 neutralizing autoantibodies to IL-17A in aged AIRE-deficient BALB/c mice – the first report of any target shared by these human and murine AIRE-deficiency states. We conclude that autoimmunization against cytokines in AIRE deficiency is not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation. PMID:23379432

  17. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Cotler, Scott J; Kanji, Kiran; Keshavarzian, Ali; Jensen, Donald M; Jakate, Shriram

    2004-10-01

    The aim of this study is to evaluate the prevalence and the clinical and histologic correlates of autoantibodies in patients with nonalcoholic steatohepatitis (NASH). Antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) have been identified in patients with NASH. The significance of autoantibodies in NASH is uncertain. Clinical data from patients with a histologic diagnosis of NASH at a university hospital in Chicago, Illinois between January 1999 and April 2003 were reviewed retrospectively. Seventy-four patients who were tested for autoantibodies and had no history of alcohol abuse or a systemic autoimmune disease were included. Demographic information and laboratory data were collected. Autoantibody titers > or = 1:40 were considered positive. A single pathologist reviewed all liver biopsies and scored features of NASH and identified characteristics of autoimmune hepatitis. Thirty-four percent of patients with NASH had positive ANA titers and 6% were ASMA positive. Demographic and laboratory parameters did not differ by ANA status, except that women were more frequently ANA positive then men (P = 0.01). The severity of steatosis, inflammation, and fibrosis on liver biopsy were similar in the ANA positive and negative groups. Only 15% of ANA positive patients with NASH had a plasma cell infiltrate on liver biopsy and there was no difference in the frequency of histologic features of autoimmune hepatitis between ANA positive and negative patients. Antinuclear antibodies are common in patients with NASH and most frequently represent a nonspecific antibody response that is not associated with the pattern or severity of injury on liver biopsy.

  18. Myositis-specific autoantibodies and their association with malignancy in Italian patients with polymyositis and dermatomyositis.

    Science.gov (United States)

    Ceribelli, Angela; Isailovic, Natasa; De Santis, Maria; Generali, Elena; Fredi, Micaela; Cavazzana, Ilaria; Franceschini, Franco; Cantarini, Luca; Satoh, Minoru; Selmi, Carlo

    2017-02-01

    This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1γ/α, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1γ was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1γ/α (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1γ/α in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.

  19. Demyelinating polyneuropathy, dermatomyositis, and interstitial pneumonitis associated with autoantibody against melanoma differentiation-associated gene 5

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Chiu

    2017-01-01

    Full Text Available Patients with serum anti-melanoma differentiation-associated gene 5 autoantibodies (anti-MDA5 are related to amyopathic dermatomyositis, especially in Asians. Here, we present a 46-year-old woman who was diagnosed with anti-MDA5-mediated demyelinating polyneuropathy clinically mimicking dermatomyositis. She had rapid progression of interstitial pneumonitis complicated with Pneumocystis jirovecii and Aspergillus pneumonia with septic shock. It is rare that patients with anti-MDA5-positive dermatomyositis present as demyelinating polyneuropathy.

  20. Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis.

    Science.gov (United States)

    McLeod, Olga; Silveira, Angela; Fredrikson, Gunilla N; Gertow, Karl; Baldassarre, Damiano; Veglia, Fabrizio; Sennblad, Bengt; Strawbridge, Rona J; Larsson, Malin; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Ohrvik, John; Nilsson, Jan; Hamsten, Anders

    2014-01-01

    Experimental studies have suggested that autoimmunity is involved in atherosclerosis and provided evidence that both protective and pro-atherogenic immune responses exist. This concept has received support from small clinical studies implicating autoantibodies directed against apolipoprotein B-100 (apoB-100) in human atherosclerosis. We examined circulating autoantibodies directed against native and malondialdehyde (MDA)-modified epitope p210 of apoB-100 (IgG-p210nat and IgM-p210MDA) in relation to early atherosclerosis in a large, European longitudinal cohort study of healthy high-risk individuals. IgG-p210nat and IgM-p210MDA were quantified in baseline plasma samples of 3430 participants in the IMPROVE study and related to composite and segment-specific measures of severity and rate of progression of carotid intima-media thickness (cIMT) determined at baseline and after 30 months. IgM-p210MDA autoantibody levels were independently related to several cIMT measures both in the common carotid artery and in the carotid bulb, including measures of cIMT progression, higher levels being associated with lower cIMT or slower cIMT progression. Consistent inverse relationships were also found between plasma levels of IgG-p210nat and baseline composite measures of cIMT. These associations disappeared when adjusting for established and emerging risk factors, and there were no associations with rate of cIMT progression besides in certain secondary stratified analyses. The present study provides further evidence of involvement of autoantibodies against native and MDA-modified apoB-100 peptide 210 in cardiovascular disease in humans and demonstrates that these associations are present already at a subclinical stage of the disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Tumour auto-antibody screening: performance of protein microarrays using SEREX derived antigens

    International Nuclear Information System (INIS)

    Stempfer, René; Weinhäusel, Andreas; Syed, Parvez; Vierlinger, Klemens; Pichler, Rudolf; Meese, Eckart; Leidinger, Petra; Ludwig, Nicole; Kriegner, Albert; Nöhammer, Christa

    2010-01-01

    The simplicity and potential of minimal invasive testing using serum from patients make auto-antibody based biomarkers a very promising tool for use in diagnostics of cancer and auto-immune disease. Although several methods exist for elucidating candidate-protein markers, immobilizing these onto membranes and generating so called macroarrays is of limited use for marker validation. Especially when several hundred samples have to be analysed, microarrays could serve as a good alternative since processing macro membranes is cumbersome and reproducibility of results is moderate. Candidate markers identified by SEREX (serological identification of antigens by recombinant expression cloning) screenings of brain and lung tumour were used for macroarray and microarray production. For microarray production recombinant proteins were expressed in E. coli by autoinduction and purified His-tag (histidine-tagged) proteins were then used for the production of protein microarrays. Protein arrays were hybridized with the serum samples from brain and lung tumour patients. Methods for the generation of microarrays were successfully established when using antigens derived from membrane-based selection. Signal patterns obtained by microarrays analysis of brain and lung tumour patients' sera were highly reproducible (R = 0.92-0.96). This provides the technical foundation for diagnostic applications on the basis of auto-antibody patterns. In this limited test set, the assay provided high reproducibility and a broad dynamic range to classify all brain and lung samples correctly. Protein microarray is an efficient means for auto-antibody-based detection when using SEREX-derived clones expressing antigenic proteins. Protein microarrays are preferred to macroarrays due to the easier handling and the high reproducibility of auto-antibody testing. Especially when using only a few microliters of patient samples protein microarrays are ideally suited for validation of auto-antibody

  2. Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review.

    Science.gov (United States)

    Ma, Wen-Tao; Chang, Christopher; Gershwin, M Eric; Lian, Zhe-Xiong

    2017-09-01

    The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. Both humoral and cellular elements of the adaptive immune system play a role in the pathogenesis of autoimmune diseases and the presence of autoantibodies have been detected in most but not all autoimmune diseases before the appearance of clinical symptoms. In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well. This observation is intriguing because it suggests that we can, to some degree, predict who may or may not develop autoimmune diseases. However, the role of autoantibodies in the pathogenesis of autoimmune diseases, whether they actually affect disease progression or are merely an epiphenomenon is still not completely clear in many autoimmune diseases. Because of these gaps in our knowledge, the ability to accurately predict a future autoimmune disease can only be considered a relative risk factor. Importantly, it raises the critical question of defining other events that may drive a patient from a preclinical to a clinical phase of disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Characterization of autoantibodies in autoimmune hemolytic anemia following treatment with interferon alfa

    International Nuclear Information System (INIS)

    Bencomo Hernandez, Antonio; Gutierrez Diaz, Adys; Avila Cabrera, Onel; Rodriguez, Luis Ramon

    2012-01-01

    We studied 13 patients with chronic myeloid leukemia and autoimmune hemolytic anemia induced by interferon alfa. They underwent tests for immune protein detection and characterization of IgG subclasses in RBCs by direct antiglobulin test (PAD) and the microplate technique. Also they were applied ELISA test for quantifying immunoglobulins in the red blood cells. It was detected the presence of IgG and C3 in 53.84 % of cases, IgG alone in 23.07 % and in 15.38 % were identified IgG and IgA autoantibodies. In 11 patients the presence of IgG1 was showed and also in one case the subclass IgG3 autoantibodies was identified. The ELISA detected antibodies at concentrations of 183 IgG molecules per erythrocyte in a patient with negative PAD. In high-grade hemolysis patients, it was found a concentration of autoantibodies between 1 500 and 3 180 molecules of IgG per erythrocyte, while in low-grade hemolysis patients it behaved between 183 and 1 000 molecules. There was a negative correlation between Hb and plasma haptoglobin values with the number of IgG molecules per erythrocyte and a positive correlation between the latter with the reticulocyte count

  4. Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity

    Directory of Open Access Journals (Sweden)

    Robinson Nicola J

    2009-02-01

    Full Text Available Abstract Background Celiac disease (CD occurs in as many as 1 in 80 pregnant women and is associated with poor pregnancy outcome, but it is not known if this is an effect on maternal nutrient absorption or, alternatively, if the placenta is an autoimmune target. The major autoantigen, tissue transglutaminase (tTG, has previously been shown to be present in the maternal-facing syncytiotrophoblast plasma membrane of the placenta. Methods ELISA was used to demonstrate the presence of antibodies to tissue transglutaminase in a panel of CD sera. Immunohistochemistry was used to evaluate the binding of IgA autoantibodies from CD serum to term placenta. In addition, novel direct binding and activity assays were developed to mimic the in vivo exposure of the villous placenta to maternal autoantibody. Results and Discussion CD IgA autoantibodies located to the syncytial surface of the placenta significantly more than IgA antibodies in control sera (P Conclusion These data indicate that direct immune effects in untreated CD women may compromise placental function.

  5. Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management.

    Science.gov (United States)

    Chiang, Chun-Pin; Yu-Fong Chang, Julia; Wang, Yi-Ping; Wu, Yu-Hsueh; Lu, Shin-Yu; Sun, Andy

    2018-02-19

    Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia, respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the 320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti-mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320 OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%, 7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and folic acid deficiencies, and abnormally high serum homocysteine level, respectively. Therefore, it is very important to examine the serum autoantibody, hematinic and homocysteine levels in OLP patients before starting the treatments for OLP patients. Because OLP is an immunologically-mediated disease, corticosteroids are the drugs of choice for treatment of OLP. Copyright © 2018. Published by Elsevier B.V.

  6. Autoantibodies in renal diseases – clinical significance and recent developments in serological detection

    Directory of Open Access Journals (Sweden)

    Gianna eKirsztajn

    2015-05-01

    Full Text Available Autoimmune dysfunctions are the bête noire in a range of debilitating nephropathies. Autoimmune-mediated damage to the kidneys can be triggered by autoantibodies directed against specific proteins or renal structures, for example the phospholipase A2 receptor or the glomerular basement membrane, resulting in glomerular diseases such as primary membranous nephropathy or Goodpasture’s disease. Moreover, secondary damage to the kidney can be part of the wide-reaching effects of systemic autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE – the latter counts lupus nephritis among its most severe manifestations. Systemic autoimmune diseases are characterized by non-organ-specific autoantibodies, directed for example against neutrophil cytoplasmic antigens in systemic vasculitis and against double-stranded DNA and nucleosomes in SLE.A large variety of innovative and highly specific and sensitive autoantibody tests have been developed in the last years that are available to identify autoimmune kidney diseases at an early stage. Thus, serological in vitro diagnostics allow for appropriate interventional therapy in order to prevent disease progression often resulting in need of dialysis and transplantation.

  7. Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon.

    Science.gov (United States)

    Mueller, Markus; Gschwandtner, Michael E; Gamper, Jutta; Giurgea, Georgiana-Aura; Charwat-Resl, Silvia; Kiener, Hans P; Smolen, Josef S; Perkmann, Thomas; Koppensteiner, Renate; Schlager, Oliver

    2016-02-02

    In incipient Raynaud phenomenon, nailfold capillaroscopy and autoantibody tests are obtained to screen for an emerging connective tissue disease. Whether the presence of abnormal nailfold capillaries and autoantibodies are related to mortality in patients with incipient Raynaud phenomenon is not known. In 2958 consecutive patients (78% women, median age 45 years) with incipient Raynaud phenomenon without previously known connective tissue disease, nailfold capillaroscopy and laboratory tests for antinuclear antibodies (ANA) and ANA subsets were obtained at initial presentation. During a median follow-up period of 9.3 years, 227 women (9.9% of female patients) and 129 men (20% of male patients) with Raynaud phenomenon died. In comparison with a demographically matched standard population, survival was poorer in patients with Raynaud phenomenon (log-rank test PRaynaud phenomenon, mortality was higher in men than in women (PRaynaud phenomenon, male sex, age, and serum creatinine are related to mortality. Abnormal nailfold capillaries and autoantibodies are associated with an increase in all-cause mortality in female patients, but not in male patients with Raynaud phenomenon. © 2016 American Heart Association, Inc.

  8. Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes

    Science.gov (United States)

    Link, Maire; Wolff, Anette S. B.; Meager, Anthony; Tserel, Liina; Org, Tõnis; Murumägi, Astrid; Uibo, Raivo; Willcox, Nick; Trebušak Podkrajšek, Katarina; Battelino, Tadej; Lobell, Anna; Kämpe, Olle; Lima, Kari; Meloni, Antonella; Ergun-Longmire, Berrin; Maclaren, Noel K.; Perheentupa, Jaakko; Krohn, Kai J. E.; Scott, Hamish S.; Husebye, Eystein S.; Peterson, Pärt

    2008-01-01

    Neutralizing autoantibodies to type I, but not type II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead to defects in thymic T-cell selection. Combining genome-wide expression array with real time RT-PCR assays, we here demonstrate that antibodies against IFN-α cause highly significant down-regulation of interferon-stimulated gene expression in cells from APECED patients' blood by blocking their highly dilute endogenous IFNs. This down-regulation was lost progressively as these APECED cells matured in cultures without neutralizing autoantibodies. Most interestingly, a rare APECED patient with autoantibodies to IFN-ω but not IFN-α showed a marked increase in expression of the same interferon-stimulated genes. We also report unexpected increases in serum CXCL10 levels in APECED. Our results argue that the breakdown of tolerance to IFNs in AIRE deficiency is associated with impaired responses to them in thymus, and highlight APECED as another autoimmune disease with associated dysregulation of IFN activity. PMID:18606876

  9. [Interstitial lung disease-associated with amyopathic dermatomyositis and anti-MDA5 autoantibodies].

    Science.gov (United States)

    Gerfaud-Valentin, M; Ahmad, K; Piegay, F; Fabien, N; Raphanel, B; Cordier, J-F; Cottin, V

    2014-11-01

    Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies is a rare and very recently described clinical entity. A 58-year-old woman was admitted with subacute onset of dyspnea (NYHA class IV) associated with cough, oligoarthritis of the wrists, myalgia and intermittent fever. Examination demonstrated skin lesions with heliotrope rash, Gottron's papules, "mechanics hands", and basal inspiratory crackles on lung auscultation. Pulmonary function tests showed a restrictive ventilatory defect, with decreased carbon monoxide diffusion capacity and marked hypoxemia (PaO2 61 mmHg). The chest high-resolution computed tomography appearances were consistent with organizing pneumonia. Bronchoalveolar lavage differential cell count demonstrated 22 % neutrophils. Serum creatine kinase and electromyography were normal ; the serum ferritin level was elevated. Antinuclear antibodies were present and anti-MDA5 autoantibodies were identified. Significant improvement was obtained with systemic corticosteroids, later converted to mycophenolate mofetil as a steroid-sparing agent. Amyopathic dermatomyositis associated with anti-MDA5 autoantibodies shares some characteristics with those associated with anti-synthetase antibodies. Muscular involvement may be mild or absent. Early diagnosis and treatment may improve outcome. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  10. A simple and fast non-radioactive bridging immunoassay for insulin autoantibodies.

    Science.gov (United States)

    Kikkas, Ingrid; Mallone, Roberto; Tubiana-Rufi, Nadia; Chevenne, Didier; Carel, Jean Claude; Créminon, Christophe; Volland, Hervé; Boitard, Christian; Morel, Nathalie

    2013-01-01

    Type 1 diabetes (T1D) is an autoimmune disease which results from the destruction of pancreatic beta cells. Autoantibodies directed against islet antigens are valuable diagnostic tools. Insulin autoantibodies (IAAs) are usually the first to appear and also the most difficult to detect amongst the four major islet autoantibodies. A non-radioactive IAA bridging ELISA was developed to this end. In this assay, one site of the IAAs from serum samples is bound to a hapten-labeled insulin (GC300-insulin), which is subsequently captured on anti-GC300 antibody-coated 96-well plates. The other site of the IAAs is bound to biotinylated insulin, allowing the complex to be detected by an enzyme-streptavidin conjugate. In the present study, 50 serum samples from patients with newly diagnosed T1D and 100 control sera from non-diabetic individuals were analyzed with our new assay and the results were correlated with an IAA radioimmunoassay (RIA). Using IAA bridging ELISA, IAAs were detected in 32 out of 50 T1D children, whereas with IAA RIA, 41 out of 50 children with newly diagnosed T1D were scored as positive. In conclusion, the IAA bridging ELISA could serve as an attractive approach for rapid and automated detection of IAAs in T1D patients for diagnostic purposes.

  11. Changes of thyroid function, autoantibodies, bone mineral density and bone metabolism indexes in patients with hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2016-07-01

    Full Text Available Objective: To investigate the changes of thyroid function, autoantibodies, bone mineral density and bone metabolism in patients with hyperthyroidism. Methods: A total of 216 cases of hyperthyroidism in our hospital from December 2015 to January 2015 were selected as the case group, 216 cases of healthy people selected the same period in our hospital physical examination center as the control group, detected thyroid function, autoantibodies, bone mineral density and bone metabolism indexes of all the studied subjects and compared with each other. Results: In this study, it was found that diastolic blood pressure, BMI, triglyceride, total cholesterol, HDL-C, VLDL-C, TSH were all significantly lower than the control group (P<0.05, systolic blood pressure, LDL-C, GLU, T3, T4, FT3, FT4, HTG, TG-Ab, TPO-Ab in case group were significantly higher than the control group (P<0.05. Right calcaneal speed of sound (SOS in case group was significantly lower than the control group (P<0.05, BGP, PTH in case group were significantly higher than the control group (P<0.05. Conclusions: Hyperthyroidism can cause thyroid hormone levels abnormal, abnormal increase autoantibodies, decrease bone density, bone metabolism actively, easy to form osteoporosis, clinical treatment of hyperthyroidism in the same time, should actively prevent the occurrence of osteoporosis

  12. Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum of autistic children impair in vitro models of synaptic plasticity in rat hippocampus.

    Science.gov (United States)

    Gonzalez-Gronow, Mario; Cuchacovich, Miguel; Francos, Rina; Cuchacovich, Stephanie; Blanco, Angel; Sandoval, Rodrigo; Gomez, Cristian Farias; Valenzuela, Javier A; Ray, Rupa; Pizzo, Salvatore V

    2015-10-15

    Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high titers, but no autoantibodies of the IgM class. IgA autoantibodies act as serine proteinases and degrade MBP in vitro. They also induce a decrease in long-term potentiation in the hippocampi of rats either perfused with or previously inoculated with this IgA. Because this class of autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we hypothesized a similar pathological role for them in ASD. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  14. The production of cross-reactive autoantibodies that bind to bovine serum albumin in mice administered reducing sugars by subcutaneous injection

    OpenAIRE

    Park, Ji-Hun; Choi, Tae-Saeng

    2015-01-01

    Introduction In a previous study, we identified the formation of cross-reactive autoantibodies that bound to bovine serum albumin (BSA) in a D-galactose-induced aging mouse model. Aim of the study In this study, we investigated the effect of other reducing sugars (namely, glucose and fructose) on the formation of autoantibodies. The effects of concentration and route of administration on the formation of autoantibodies were examined in detail. Material and methods Three concentrations (100, 5...

  15. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Licarete Emilia

    2012-04-01

    Full Text Available Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA, but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50, Crohn's disease (CD, n = 50, ulcerative colitis (UC, n = 50, bullous pemphigoid (BP, n = 76, and pemphigus vulgaris (PV, n = 42 and healthy donors (n = 245. Results By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005, allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%, 2 CD (4%; 95% CI: 0%-9.43%, 8 UC (16%; 95% CI: 5.8%-26%, 2 BP (2.63%; 95% CI: 0%-6.23%, and 4 PV (9.52%; 95% CI: 0%-18.4% patients as well as from 4 (1.63%; 95% CI: 0%-3.21% healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Conclusions Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should

  16. IgE autoantibodies and their association with the disease activity and phenotype in bullous pemphigoid: a systematic review.

    Science.gov (United States)

    Saniklidou, Ariadne Hadjikyriacou; Tighe, Patrick J; Fairclough, Lucy C; Todd, Ian

    2018-01-01

    Bullous pemphigoid (BP) is the most common autoimmune skin disease of blistering character. The underlying pathophysiological mechanism involves an immune attack, usually by IgG class autoantibodies, on the autoantigen BP 180/BPAg2, which is a type XVII collagen (COL17) protein acting as the adhesion molecule between the epidermis and the basement membrane of the dermis. About 40 years ago, following consistent findings of elevated total serum IgE levels in BP patients, it was hypothesized that IgE may be involved in the pathophysiology of BP. Our objective was to determine whether there is strong evidence for an association between IgE class autoantibodies and the clinical severity or phenotype of BP. Three databases were searched for relevant studies and appropriate exclusion and inclusion criteria were applied. Data was extracted and assessed in relation to the study questions concerning the clinical significance of IgE autoantibodies in BP. Nine studies found that anti-BP180 autoantibodies of IgE class are associated with increased severity of BP, whereas two studies did not find such an association. The number of studies which found an association between higher IgE autoantibody levels and the erythematous urticarial phenotype of BP (5) was equal in number to the studies which found no such association (5). In conclusion, higher serum IgE autoantibody levels are associated with more severe clinical manifestations of BP. There is insufficient evidence to support higher IgE autoantibody levels being associated with specific clinical phenotypes of BP.

  17. Calcinosis in juvenile dermatomyositis is influenced by both anti-NXP2 autoantibody status and age at disease onset.

    Science.gov (United States)

    Tansley, Sarah L; Betteridge, Zoe E; Shaddick, Gavin; Gunawardena, Harsha; Arnold, Katie; Wedderburn, Lucy R; McHugh, Neil J

    2014-12-01

    Calcinosis is a major cause of morbidity in JDM and has previously been linked to anti-NXP2 autoantibodies, younger age at disease onset and more persistent disease activity. This study aimed to investigate the clinical associations of anti-NXP2 autoantibodies in patients with JDM stratified by age at disease onset. A total of 285 patients with samples and clinical data were recruited via the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-NXP2 was determined by both immunoprecipitation and ELISA. Logistic regression analysis was performed to assess the age-dependent relationship between anti-NXP2 and the development of calcinosis and disease activity measures. We identified anti-NXP2 autoantibodies in 56 patients (20%). While in all patients younger age at disease onset was associated with an increased risk of calcinosis and this relationship was nearly linear, anti-NXP2 autoantibodies substantially increased the risk of calcinosis across all ages (P = 0.025) and were detectable prior to calcinosis development. Children with anti-NXP2 autoantibodies had a greater degree of weakness (median lowest ever Childhood Myositis Assessment Score 29.6 vs 42) and were less likely to be in remission at 2 years post-diagnosis. No difference in disease activity was seen 4 years post-diagnosis. Children diagnosed at a young age have a high risk of calcinosis regardless of autoantibody status. However, the presence of anti-NXP2 autoantibodies substantially increases the risk of calcinosis across all ages and is associated with disease severity. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  18. Predictive Characteristics of Diabetes-Associated Autoantibodies Among Children With HLA-Conferred Disease Susceptibility in the General Population

    Science.gov (United States)

    Siljander, Heli T.A.; Simell, Satu; Hekkala, Anne; Lähde, Jyrki; Simell, Tuula; Vähäsalo, Paula; Veijola, Riitta; Ilonen, Jorma; Simell, Olli; Knip, Mikael

    2009-01-01

    OBJECTIVE As data on the predictive characteristics of diabetes-associated autoantibodies for type 1 diabetes in the general population are scarce, we assessed the predictive performance of islet cell autoantibodies (ICAs) in combination with autoantibodies against insulin (IAAs), autoantibodies against GAD, and/or islet antigen 2 for type 1 diabetes in children with HLA-defined disease predisposition recruited from the general population. RESEARCH DESIGN AND METHODS We observed 7,410 children from birth (median 9.2 years) for β-cell autoimmunity and diabetes. If a child developed ICA positivity or diabetes, the three other antibodies were measured in all samples available from that individual. Persistent autoantibody positivity was defined as continued positivity in at least two sequential samples including the last available sample. RESULTS Pre-diabetic ICA positivity was observed in 1,173 subjects (15.8%), 155 of whom developed type 1 diabetes. With ICA screening, 86% of 180 progressors (median age at diagnosis 5.0 years) were identified. Positivity for four antibodies was associated with the highest disease sensitivity (54.4%) and negative predictive values (98.3%) and the lowest negative likelihood ratio (0.5). The combination of persistent ICA and IAA positivity resulted in the highest positive predictive value (91.7%), positive likelihood ratio (441.8), cumulative disease risk (100%), and specificity (100%). Young age at seroconversion, high ICA level, multipositivity, and persistent positivity for IAA were significant risk markers for type 1 diabetes. CONCLUSIONS Within the general population, the combination of HLA and autoantibody screening resulted in disease risks that are likely to be as high as those reported among autoantibody-positive siblings of children with type 1 diabetes. PMID:19755526

  19. Encoding information into precipitation structures

    International Nuclear Information System (INIS)

    Martens, Kirsten; Bena, Ioana; Droz, Michel; Rácz, Zoltan

    2008-01-01

    Material design at submicron scales would be profoundly affected if the formation of precipitation patterns could be easily controlled. It would allow the direct building of bulk structures, in contrast to traditional techniques which consist of removing material in order to create patterns. Here, we discuss an extension of our recent proposal of using electrical currents to control precipitation bands which emerge in the wake of reaction fronts in A + + B – → C reaction–diffusion processes. Our main result, based on simulating the reaction–diffusion–precipitation equations, is that the dynamics of the charged agents can be guided by an appropriately designed time-dependent electric current so that, in addition to the control of the band spacing, the width of the precipitation bands can also be tuned. This makes straightforward the encoding of information into precipitation patterns and, as an amusing example, we demonstrate the feasibility by showing how to encode a musical rhythm

  20. Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes.

    Science.gov (United States)

    de Moel, Emma C; Derksen, Veerle F A M; Stoeken, Gerrie; Trouw, Leendert A; Bang, Holger; Goekoop, Robbert J; Speyer, Irene; Huizinga, Tom W J; Allaart, Cornelia F; Toes, René E M; van der Woude, Diane

    2018-02-26

    The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on (1) change in disease activity score (DAS)44 between 0 and 4 months, (2) initial drug-free remission (DFR, drug-free DAS44 profile at baseline had a significantly better early treatment response: ΔDAS 0-4 months of 1-2, 3-4, and 5-6 vs 7-8 isotypes, -1.5 (p profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar trends were observed. A broad baseline autoantibody profile is associated with a better early treatment response. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity, which could make the underlying disease processes initially more suppressible by medication. The lack of association with long-term sustained DFR suggests that the relevance of the baseline autoantibody profile diminishes over time. ISRCTN11916566 . Registered on 7

  1. Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study

    DEFF Research Database (Denmark)

    Pedersen, Inge Bülow; Laurberg, Peter; Knudsen, Nils

    2008-01-01

    antibodies is limited. Aim: To evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab. Material and methods: In a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects...... from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected. Results: Data were...... analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPC-Ab status...

  2. Pathogenesis of Renal Disease in Systemic Lupus Erythematosus—The Role of Autoantibodies and Lymphocytes Subset Abnormalities

    Directory of Open Access Journals (Sweden)

    Desmond Y. H. Yap

    2015-04-01

    Full Text Available Lupus nephritis (LN is a common and severe organ manifestation of systemic lupus erythematosus (SLE, and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberration of T lymphocytes, especially the T-helper subsets, is also highly pertinent in the development of LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, TReg and follicular T-helper cells. The growing knowledge on these autoantibodies and lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and hence help devise better strategies for disease monitoring and treatment.

  3. Comparison of Serum Autoantibodies to Desmogleins I, III in Patients with Oral Lichen Planus and Healthy Controls.

    Science.gov (United States)

    Gholizadeh, Narges; Khoini Poorfar, Hossein; TaghaviZenouz, Ali; Vatandoost, Masoumeh; Mehdipour, Masoumeh

    2015-01-01

    Lichen planus is a mucocutaneous disease which is relatively common and in 30-70% of patients, mucosal lesions can be seen and known as a precancerous lesion but its etiology is not completely understood. Desmogleins I and III are the main desmosomal transmembrane proteins. These proteins have been identified as the autoantigen of the autoimmune disease. The aim of this study was evaluation of serum autoantibodies against desmogleins Ι, ΙΙΙ in oral lichen planus . We attempted to determine the etiology of this disease with evaluation of these serum factors. Thirty-five patients with oral lichen planus and 35 healthy controls were recruited and tested for serum autoantibodies against desmogleins Ι, ΙΙΙ and indirect immunofluorescence also performed. Data were analyzed by statistical-analytical methods (Independent sample t -test) with using the SPSS.15 software. Serum autoantibody against desmoglein Ι had no significant difference in the two groups ( P =0.31 ) but significant increase in serum autoantibody to desmoglein ΙΙΙ was found in patients with oral lichen planus ( P =0.00) . It seems that autoantibody against desmoglein III has a significant role in the pathogenesis of oral lichen planus.

  4. Thyroid Autoantibodies in the Cerebrospinal Fluid of Subjects with and without Thyroid Disease: Implications for Hashimoto’s Encephalopathy

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    Ioannis Ilias

    2015-01-01

    Full Text Available Introduction. Plasma antithyroid peroxidase (anti-TPO and anti-thyroglobulin antibodies (anti-Tg are widely used in the diagnosis of autoimmune thyroiditis. No research has compared anti-TPO and anti-Tg both in plasma and cerebrospinal fluid (CSF of healthy individuals vis-à-vis patients with thyroid disease. Methods. We measured anti-TPO and anti-Tg antibodies in plasma and CSF in nine subjects (mean age ± SD: 73 ± 6 years with hypothyroidism and nine subjects (mean age ± SD: 73 ± 8 years without thyroid disease. Results. The concentration of anti-TPO autoantibodies in CSF was very low compared to plasma in both subjects with thyroid and without thyroid disease (P=0.007. CSF anti-Tg autoantibodies titers were very low compared to the plasma in subjects with thyroid disease (P=0.004, whereas, in subjects without thyroid disease, this difference did not reach statistical significance (P=0.063. Conclusions. Thyroid autoantibodies levels were low in plasma and CSF; we did not observe any transfer of thyroid autoantibodies from the peripheral blood to the CSF. Therefore, regarding Hashimoto’s encephalopathy, where elevated antithyroid autoantibodies are often measured in blood, it is more likely that thyroiditis and encephalopathy represent nonspecific, but distinct, events of an aggressive immune system.

  5. Association among Complement Factor H Autoantibodies, Deletions of CFHR, and the Risk of Atypical Hemolytic Uremic Syndrome

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    Hong Jiang

    2016-12-01

    Full Text Available To evaluate the association among complement factor H-related (CFHRs gene deficiency, complement factor H (CFH autoantibodies, and atypical hemolytic uremic syndrome (aHUS susceptibility. EMBASE, PubMed, and the ISI Web of Science databases were searched for all eligible studies on the relationship among CFHRs deficiency, anti-FH autoantibodies, and aHUS risk. Eight case-control studies with 927 cases and 1182 controls were included in this study. CFHR1 deficiency was significantly associated with an increased risk of aHUS (odds ratio (OR = 3.61, 95% confidence interval (95% CI, 1.96, 6.63, p < 0.001, while no association was demonstrated in individuals with only CFHR1/R3 deficiency (OR = 1.32, 95% CI, 0.50, 3.50, p = 0.56. Moreover, a more significant correlation was observed in people with both FH-anti autoantibodies and CFHR1 deficiency (OR = 11.75, 95% CI, 4.53, 30.44, p < 0.001 in contrast to those with only CFHR1 deficiency. In addition, the results were essentially consistent among subgroups stratified by study quality, ethnicity, and gene detection methods. The present meta-analysis indicated that CFHR1 deletion was significantly associated with the risk of aHUS, particularly when combined with anti-FH autoantibodies, indicating that potential interactions among CFHR1 deficiency and anti-FH autoantibodies might impact the risk of aHUS.

  6. The production of cross-reactive autoantibodies that bind to bovine serum albumin in mice administered reducing sugars by subcutaneous injection.

    Science.gov (United States)

    Park, Ji-Hun; Choi, Tae-Saeng

    2015-01-01

    In a previous study, we identified the formation of cross-reactive autoantibodies that bound to bovine serum albumin (BSA) in a D-galactose-induced aging mouse model. In this study, we investigated the effect of other reducing sugars (namely, glucose and fructose) on the formation of autoantibodies. The effects of concentration and route of administration on the formation of autoantibodies were examined in detail. Three concentrations (100, 500, and 1,000 mg/kg) of reducing sugars were tested. The effects of different routes of administration (subcutaneous, oral, and intraperitoneal) on the formation of autoantibodies were also analysed. The immunoreactivities of serum samples from mice treated with reducing sugars were analysed by an enzyme-linked immunosorbent assay (ELISA) using BSA or mouse serum albumin antigens (MSA). Repeated subcutaneous administration of all reducing sugars lead to autoantibody formation in a concentration-dependent manner. However, these autoantibodies did not cross-react with MSA, and simultaneous treatment of aminoguanidine with reducing sugars did not show any inhibitory effects on the formation of autoantibodies. No autoantibodies were detected after oral or intraperitoneal administration of reducing sugars. Immunohistochemistry data showed that the target antigen(s) of the autoantibodies were present only in the skin tissue of mice treated with reducing sugars. Our results show that administration of reducing sugars by subcutaneous injection leads to the formation of autoantibodies that cross-react with BSA; the formation and target antigen(s) of the autoantibodies may originate from within the skin tissue treated with the reducing sugars.

  7. Measurements of auto-antibodies to α-synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease.

    Science.gov (United States)

    Akhtar, Rizwan S; Licata, Joseph P; Luk, Kelvin C; Shaw, Leslie M; Trojanowski, John Q; Lee, Virginia M-Y

    2018-03-03

    Biomarkers for α-synuclein are needed for diagnosis and prognosis in Parkinson's disease (PD). Endogenous auto-antibodies to α-synuclein could serve as biomarkers for underlying synucleinopathy, but previous assessments of auto-antibodies have shown variability and inconsistent clinical correlations. We hypothesized that auto-antibodies to α-synuclein could be diagnostic for PD and explain its clinical heterogeneity. To test this hypothesis, we developed an enzyme-linked immunosorbent assay for measuring α-synuclein auto-antibodies in human samples. We evaluated 69 serum samples (16 healthy controls (HC) and 53 PD patients) and 145 CSF samples (52 HC and 93 PD patients) from our Institution. Both serum and CSF were available for 24 participants. Males had higher auto-antibody levels than females in both fluids. CSF auto-antibody levels were significantly higher in PD patients as compared to HC, whereas serum levels were not significantly different. CSF auto-antibody levels did not associate with amyloid-β 1-42 , total tau, or phosphorylated tau. CSF auto-antibody levels correlated with performance on the Montreal Cognitive Assessment, even when controlled for CSF amyloidβ 1-42 . CSF hemoglobin levels, as a proxy for contamination of CSF by blood during lumbar puncture, did not influence these observations. Using recombinant α-synuclein with N- and C-terminal truncations, we found that CSF auto-antibodies target amino acids 100 through 120 of α-synuclein. We conclude that endogenous CSF auto-antibodies are significantly higher in PD patients as compared to HC, suggesting that they could indicate the presence of underlying synucleinopathy. These auto-antibodies associate with poor cognition, independently of CSF amyloidβ 1-42 ., and target a select C-terminal region of α-synuclein. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Critical Role of the Neonatal Fc Receptor (FcRn) in the Pathogenic Action of Antimitochondrial Autoantibodies Synergizing with Anti-desmoglein Autoantibodies in Pemphigus Vulgaris.

    Science.gov (United States)

    Chen, Yumay; Chernyavsky, Alex; Webber, Robert J; Grando, Sergei A; Wang, Ping H

    2015-09-25

    Pemphigus vulgaris (PV) is a life-long, potentially fatal IgG autoantibody-mediated blistering disease targeting mucocutaneous keratinocytes (KCs). PV patients develop pathogenic anti-desmoglein (Dsg) 3 ± 1 and antimitochondrial antibodies (AMA), but it remained unknown whether and how AMA enter KCs and why other cell types are not affected in PV. Therefore, we sought to elucidate mechanisms of cell entry, trafficking, and pathogenic action of AMA in PV. We found that PVIgGs associated with neonatal Fc receptor (FcRn) on the cell membrane, and the PVIgG-FcRn complexes entered KCs and reached mitochondria where they dissociated. The liberated AMA altered mitochondrial membrane potential, respiration, and ATP production and induced cytochrome c release, although the lack or inactivation of FcRn abolished the ability of PVIgG to reach and damage mitochondria and to cause detachment of KCs. The assays of mitochondrial functions and keratinocyte adhesion demonstrated that although the pathobiological effects of AMA on KCs are reversible, they become irreversible, leading to epidermal blistering (acantholysis), when AMA synergize with anti-Dsg antibodies. Thus, it appears that AMA enter a keratinocyte in a complex with FcRn, become liberated from the endosome in the cytosol, and are trafficked to the mitochondria, wherein they trigger pro-apoptotic events leading to shrinkage of basal KCs uniquely expressing FcRn in epidermis. During recovery, KCs extend their cytoplasmic aprons toward neighboring cells, but anti-Dsg antibodies prevent assembly of nascent desmosomes due to steric hindrance, thus rendering acantholysis irreversible. In conclusion, FcRn is a common acceptor protein for internalization of AMA and, perhaps, for PV autoantibodies to other intracellular antigens, and PV is a novel disease paradigm for investigating and elucidating the role of FcRn in this autoimmune disease and possibly other autoimmune diseases. © 2015 by The American Society for

  9. Somatic diversification in the heavy chain variable region genes expressed by human autoantibodies bearing a lupus-associated nephritogenic anti-DNA idiotype

    Energy Technology Data Exchange (ETDEWEB)

    Demaison, C.; Chastagner, P.; Theze, J.; Zouali, M. (Institut Pasteur, Paris (France))

    1994-01-18

    Monoclonal anti-DNA antibodies bearing a lupus nephritis-associated idiotype were derived from five patients with systemic lupus erythematosus (SLE). Genes encoding their heavy (H)-chain variable (V[sub H]) regions were cloned and sequenced. When compared with their closest V[sub h] germ-line gene relatives, these sequences exhibit a number of silent (S) and replacement (R) substitutions. The ratios of R/S mutations were much higher in the complementarity-determining regions (CDRs) of the antibodies than in the framework regions. Molecular amplification of genomic V[sub H] genes and Southern hybridization with somatic CDR2-specific oligonucleotide probes showed that the configuration of the V[sub H] genes corresponding to V[sub H] sequences in the nephritogenic antibodies is not present in the patient's own germ-line DNA, implying that the B-cell clones underwent somatic mutation in vivo. These findings, together with the characteristics of the diversity and junctional gene elements utilized to form the antibody, indicate that these autoantibodies have been driven through somatic selection processes reminiscent of those that govern antibody responses triggered by exogenous stimuli.

  10. Auto-antibodies and their association with clinical findings in women diagnosed with microscopic colitis.

    Directory of Open Access Journals (Sweden)

    Bodil Roth

    Full Text Available BACKGROUND: Microscopic colitis (MC is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. METHODS AND FINDINGS: Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS. Blood samples were collected. Anti-nuclear antibodies (ANA, anti-neutrophil cytoplasmic antibodies (ANCA, anti-Saccharomyces cerevisiae antibodies (ASCA, and antibodies against glutamic acid decarboxylase (anti-GAD, islet antigens-like insulin 2 (anti-IA2, thyroid peroxidase (anti-TPO, and thyrotropin receptor (TRAK were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59-67 years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%, ASCA IgG (13%, and anti-TPO antibodies (14% for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. CONCLUSIONS: Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC.

  11. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

    Science.gov (United States)

    Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

    2013-11-01

    Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

  12. Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis

    Science.gov (United States)

    Carmona, F David; Gutala, Ramana; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Vicente-Rabaneda, Esther; García-Hernández, Francisco J; de la Peña, Paloma García; Fernández-Castro, Mónica; Martínez-Estupiñán, Lina; Egurbide, María Victoria; Tsao, Betty P; Gourh, Pravitt; Agarwal, Sandeep K; Assassi, Shervin; Mayes, Maureen D; Arnett, Frank C; Tan, Filemon K; Martín, Javier

    2012-01-01

    Objective Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features. Methods Two case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc. Results Four out of five analysed SNPs were Significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: pFDR=6.14 × 10−4, OR=0.78; rs4963128: pFDR=6.14 × 10−4, OR=0.79; rs702966: pFDR=3.83 × 10−3, OR=0.82; and rs2246614: pFDR=3.83 × 10−3, OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant. Conclusions The results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases. PMID:21926187

  13. The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis

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    Isabela Siloşi

    2016-01-01

    Full Text Available Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA, the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP.

  14. Serum auto-antibody testing for early diagnosis of breast cancer

    International Nuclear Information System (INIS)

    Parvez, S.

    2012-01-01

    The aim of this thesis is generate prototype-tests suitable for randomized prospective validation of auto-antibody based diagnostic testing using serum samples. Tumours can stimulate the production of auto-antibodies against autologous cellular proteins known as TAAs (tumour associated antigens). This discovery has lead to a possibility of using the auto-antibodies as serological tools for the early diagnosis and management of breast cancer. The recombinant proteins expressed by the SEREX clones, identified from screenings of brain and lung tumour, were used for the production of the protein microarrays and macroarrays. The protein microarrays showed better correlation between the replicates of the serum samples used. The optimized protocols were used for the subsequent experiments. A sizable panel of 642 clone-proteins was selected by marker-screening on protein macroarrays with 38000 clones. These 642 clone-proteins were used to generate protein microarrays that differentiated serum samples from breast cancer patients and controls. Antigenic peptide motifs were identified by in-silico analysis of 642 clone-proteins and peptide arrays were generated using synthetically generated peptides. Comparative studies between protein microarrays and peptide microarrays were done using breast cancer and healthy control samples. Simultaneously, SEREX strategy was used for the identification of the immunogenic TAAs. I identified 192 cDNA expression clones derived from breast cancer tissue samples and the selection was done using breast cancer sera. The genes corresponding to these clones were found over-represented for the pathways that are known to be associated with cancers. These genes showed typical features of TAAs, like over-expression, mutations and fusion genes. (author)

  15. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism.

    Science.gov (United States)

    Wigerblad, Gustaf; Bas, Duygu B; Fernades-Cerqueira, Cátia; Krishnamurthy, Akilan; Nandakumar, Kutty Selva; Rogoz, Katarzyna; Kato, Jungo; Sandor, Katalin; Su, Jie; Jimenez-Andrade, Juan Miguel; Finn, Anja; Bersellini Farinotti, Alex; Amara, Khaled; Lundberg, Karin; Holmdahl, Rikard; Jakobsson, Per-Johan; Malmström, Vivianne; Catrina, Anca I; Klareskog, Lars; Svensson, Camilla I

    2016-04-01

    An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.

    Science.gov (United States)

    Yang, Aizhen; Zhou, Junsong; Wang, Bo; Dai, Jihong; Colman, Robert W; Song, Wenchao; Wu, Yi

    2017-12-01

    The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis. In a K/BxN serum transfer-induced arthritis (STIA) model, mice that lacked HK, pKal, or bradykinin receptors displayed protective phenotypes in joint swelling, histologic changes in inflammation, and cytokine production; however, FXII-deficient mice developed normal arthritis. Inhibition of Kal ameliorated arthritis severity and incidence at early stage STIA and reduced the levels of major cytokines in joints. In addition to releasing bradykinin from HK, Kal directly activated monocytes to produce proinflammatory cytokines, up-regulated their C5aR and FcRIII expression, and released C5a. Immune complex increased pKal activity, which led to HK cleavage. The absence of HK is associated with a decrease in joint vasopermeability. Thus, we identify a critical role for Kal in autoantibody-induced arthritis with pleiotropic effects, which suggests that it is a new target for the inhibition of arthritis.-Yang, A., Zhou, J., Wang, B., Dai, J., Colman, R. W., Song, W., Wu, Y. A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis. © FASEB.

  17. Bronchus-associated Lymphoid Tissue in Pulmonary Hypertension Produces Pathologic Autoantibodies

    Science.gov (United States)

    Colvin, Kelley L.; Cripe, Patrick J.; Ivy, D. Dunbar; Stenmark, Kurt R.

    2013-01-01

    Rationale: Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. Objectives: We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. Methods: We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Measurements and Main Results: Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3+ T cells over a core of CD45RA+ B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1+ high endothelial venules and vascular cell adhesion molecule–positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Conclusions: Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue–directed therapies may be beneficial in treating pulmonary hypertension. PMID:24093638

  18. Relationship between the autoantibody and expression of β3-adrenoceptor in lung and heart.

    Directory of Open Access Journals (Sweden)

    Guobin Miao

    Full Text Available BACKGROUND: Evidences suggest that β3 -adrenoceptor (β3-AR plays an important role in heart failure (HF, although no data is reported indicating how these effects may change with the increasing age. Pulmonary congestion and edema are the major life-threatening complications associated with HF. The purpose of this study is to explore the relationship between the anti-β3-AR autoantibody and the expression of β3-AR in the lungs and heart for both aged patients and rats with HF. METHODS: Synthetic β3-AR peptides served as the target antigens in ELISA were used to screen the anti-β3-AR autoantibody in aged patients and rats. Two aged rat models were constructed based on aortic banding and sham-operation. The expression of β3-AR mRNA and protein in the lung and heart was measured in intervention and non-intervention groups by Western blot analysis at the baseline, 5(th, 7(th, 9(th and 11(th week, respectively. RESULTS: The frequency and titer of anti-β3-AR autoantibody in aged patients and rats with HF were higher than those in the control group (p<0.05. The expression of β3-AR mRNA and protein in pulmonary tissues decreased continually from the 7(th week (p<0.05, followed by HF observed during the 9(th week. The expression of β3-AR in myocardial tissues continued to increase after the 9(th week (p<0.05, and the expression of both β3-AR mRNA and protein in the BRL group [HF group with BRL37344 (4-[-[2-hydroxy-(3-chlorophenylethyl-amino] phenoxyacetic acid (a β3-AR agonist injection] was positively correlated with BRL37344 when compared with non-BRL group (HF group without BRL37344 injection (p<0.05. CONCLUSION: Anti-β3-AR autoantibody was detected in aged patients and rats with HF. The expression of β3-AR mRNA and protein in pulmonary tissues decreased continually, and began earlier than in the heart, but its expression in myocardial tissues increased continually and could be further promoted by β3-AR agonist.

  19. Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo; Bahnsen, M

    1981-01-01

    . With increasing titres of ANA the concentration of testosterone fell. Serum concentration of testosterone correlated inversely (P less than 0.05) with plasma immunoglobulin G and A. It is concluded that both genetic and hormonal factors may influence the humoral immune response in these patients.......Titres and immunoglobulin classes of autoantibodies were examined in 69 male patients with alcoholic liver cirrhosis and the findings were related to particular human leucocyte antigens and serum concentration of testosterone. Both anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA...

  20. TSH-receptor-autoantibody-titers in untreated toxic diffuse goitres - an early indicator of relapse

    International Nuclear Information System (INIS)

    Becker, W.; Reiners, C.; Boerner, W.

    1984-01-01

    TSH-receptor-auto antibodies were determined in follow-up of 30 patients with relapse of toxic diffuse goitres, i.e. patients with Graves' disease and toxic disseminated autonomy, and in 13 patients with spontaneous remission after antithyroid drug therapy by use of a commercially available TSH-radioreceptorassay (TRAK-assay). All the patients with very high receptor-autoantibody-titers in untreated thyrotoxicosis (F > 20%) had one or more periods of hyperthyroidism or a very severe course of disease. None of these patients showed a spontaneous remission of disease. They all could be identified as Graves' patients. Patients with TRAK-titers 3% [de

  1. Binding of circulating autoantibodies in breast cancer to native and peroxynitrite-modified RNA

    Science.gov (United States)

    Tarannum, Sheereen; Arif, Zarina; Alam, Khursheed

    2013-01-01

    Peroxynitrite (ONOO−) is a powerful oxidant and nitrosative agent and has in vivo existence. The half life of ONOO− at physiological pH is less than 1 s. It can react with nucleic acids, proteins, lipoproteins, saccharides, cardiolipin, etc., and can modify their native structures. Action of ONOO−, synthesized in the authors’ laboratory by a rapid quenched flow process, on structural changes of commercially available RNA was studied by ultraviolet (UV), fluorescence, and agarose gel electrophoresis. Compared to native RNA, the ONOO−-modified RNA showed hyperchromicity at 260 nm. Furthermore, the ethidium bromide (EtBr) assisted emission intensities of ONOO−-modified RNA samples were found to be lower than the emission intensity of native RNA-EtBr complex. Agarose gel electrophoresis of ONOO−-modified RNA showed a gradual decrease in band intensities compared to native RNA, an observation clearly due to the poor intercalation of EtBr with ONOO−-modified RNA. Native and ONOO−-modified RNA samples were used as an antigen to detect autoantibodies in sera of patients with clinically defined breast cancer. Both direct binding and inhibition enzyme-linked immunosorbent assay (ELISA) confirmed the prevalence of native and 0.8 mmol/L ONOO−-modified RNA specific autoantibodies in breast cancer patients. Moreover, the progressive retardation in the mobility of immune complexes formed with native or 0.8 mmol/L ONOO−-modified RNA and affinity purified immunoglobulin G (IgG) from sera of breast cancer patients supports the findings of the direct binding and inhibition ELISAs. The peroxynitrite treatment to RNA at a higher concentration appears to have damaged or destroyed the typical epitopes on RNA and thus there was a sharp decrease in autoantibodies binding to 1.4 mmol/L ONOO−-modified RNA. It may be interpreted that cellular nitrosative stress can modify and confer immunogenicity on RNA molecules. Higher concentrations of nitrogen reactive species can

  2. Hall effect encoding of brushless dc motors

    Science.gov (United States)

    Berard, C. A.; Furia, T. J.; Goldberg, E. A.; Greene, R. C.

    1970-01-01

    Encoding mechanism integral to the motor and using the permanent magnets embedded in the rotor eliminates the need for external devices to encode information relating the position and velocity of the rotating member.

  3. Clinical and autoimmune features of a patient with autism spectrum disorder seropositive for anti-NMDA-receptor autoantibody.

    Science.gov (United States)

    Gréa, Hélène; Scheid, Isabelle; Gaman, Alexandru; Rogemond, Véronique; Gillet, Sandy; Honnorat, Jérôme; Bolognani, Federico; Czech, Christian; Bouquet, Céline; Toledano, Elie; Bouvard, Manuel; Delorme, Richard; Groc, Laurent; Leboyer, Marion

    2017-03-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are involved in ASD remains an open question. Here, we identified within a cohort an ASD patient with multiple circulating autoantibodies, including the well-characterized one against glutamate NMDA receptor (NMDAR-Ab). The patient exhibited alexithymia and previously suffered from two major depressive episodes without psychotic symptoms. Using a single molecule-based imaging approach, we demonstrate that neither NMDAR-Ab type G immunoglobulin purified from the ASD patient serum, nor that from a seropositive healthy subject, disorganize membrane NMDAR complexes at synapses. These findings suggest that the autistic patient NMDAR-Abs do not play a direct role in the etiology of ASD and that other autoantibodies directed against neuronal targets should be investigated.

  4. Dynamic changes and clinical significance of thyroid auto-antibodies before and after radioiodine treatment for Graves' disease

    International Nuclear Information System (INIS)

    Zhao Zhiying; Zhu Li; Wang Zhenghua

    2005-01-01

    To study the changes and their clinical effect of serum levels of thyroid globulin auto-antibodies (TGAb), thyroid peroxidase auto-antibodies (TPOAb) during radioiodine treatment of Graves' disease, and to investigate early therapeutic effect of radioiodine and influence factors for early hypothyroidism, 334 patients were divided into a positive group (TGAb>115IU/mL, TPOAb>34IU/mL) and a negative group (TGAb 131 I treatment. The levels of FT 3 , FT 4 , TSH, TGAb and TPOAb in serum were measured before 131 I therapy and at the 3rd, 6th, 9th, 12th month after the treatment respectively. Within one year after radioiodine treatment, 23.8% patients (48 out of 202) in the positive group and 11.4% (15 out of 132) in the negative group suffered from early hypothyroidism (P 131 I could reduce the level of thyroid auto-antibodies and promote the improvement and recovery of autoimmunity status. (authors)

  5. Increased prevalence of autoimmune disorders and autoantibodies in parents of children with opsoclonus-myoclonus syndrome (OMS).

    Science.gov (United States)

    Krasenbrink, I; Fühlhuber, V; Juhasz-Boess, I; Stolz, E; Hahn, A; Kaps, M; Hero, B; Blaes, F

    2007-06-01

    Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease in childhood which can be associated with neuroblastoma. Since autoantibodies have been detected in some patients with OMS, an autoimmune etiology is suspected. We compared the prevalence of autoimmune disorders and autoantibodies in parents of children with OMS and in a group of controls of same age and sex. Autoimmune diseases were found in 15.8% of the parents of OMS children, but only in 2.0% of the controls (pOMS parents (42.8% vs. 8.0%, pOMS parents also had significantly more autoantibodies against CNS structures than the controls (pOMS and may also hint to a genetic susceptibility for OMS.

  6. Interleukin-21, B cell activating factor and unmethylated CPG oligodeoxynucleotides synergize in promoting anti-proteinase 3 autoantibody production in vitro

    NARCIS (Netherlands)

    Lepse, Nikola; Land, Judith; Rutgers, Abraham; Kallenberg, Cornelis; Stegeman, Coen A.; Heeringa, Peter; Abdulahad, Wayel H.

    2012-01-01

    Background/Purpose: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are characterized by the presence of circulating autoantibodies that are often directed against proteinase 3 (PR3). Although the mechanisms that lead to ANCA production in AAV are not clear, bacterial

  7. Cytokines, autoantibodies and viral antibodies in premorbid and postdiagnostic sera from patients with rheumatoid arthritis: case-control study nested in a cohort of Norwegian blood donors

    DEFF Research Database (Denmark)

    Jørgensen, K T; Wiik, A; Pedersen, M

    2008-01-01

    To assess the timing of changes in cytokines, cytokine-related markers, autoantibodies and viral antibodies in the pathogenesis of rheumatoid arthritis (RA).......To assess the timing of changes in cytokines, cytokine-related markers, autoantibodies and viral antibodies in the pathogenesis of rheumatoid arthritis (RA)....

  8. Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old.

    Science.gov (United States)

    Ludvigsson, Johnny; Wahlberg, Jeanette

    2002-04-01

    Autoantibodies found in cord blood in children who later develop diabetes might be produced by the fetus. If so, continuous autoantibody production would still be expected in these children at one year of age. We decided to determine autoantibodies in cord blood and to see whether they persisted in these children at one year. Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. We conclude that most autoantibodies found in cord blood samples of children are probably passively transferred from mother to child. Antibody screening of cord blood cannot be used to predict diabetes in the general population. Infections during pregnancy may initiate an immune process related to diabetes development.

  9. Plasma autoantibodies against heat shock protein 70, enolase 1 and ribonuclease/angiogenin inhibitor 1 as potential biomarkers for cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Rucksak Rucksaken

    Full Text Available The diagnosis of cholangiocarcinoma (CCA is often challenging, leading to poor prognosis. CCA arises via chronic inflammation which may be associated with autoantibodies production. This study aims to identify IgG antibodies directed at self-proteins and tumor-associated antigens. Proteins derived from immortalized cholangiocyte cell line (MMNK1 and CCA cell lines (M055, M214 and M139 were separated using 2-dimensional electrophoresis and incubated with pooled plasma of patients with CCA and non-neoplastic controls by immunoblotting. Twenty five immunoreactive spots against all cell lines-derived proteins were observed on stained gels and studied by LC-MS/MS. Among these, heat shock protein 70 (HSP70, enolase 1 (ENO1 and ribonuclease/angiogenin inhibitor 1 (RNH1 obtained the highest matching scores and were thus selected for further validation. Western blot revealed immunoreactivity against HSP70 and RNH1 in the majority of CCA cases and weakly in healthy individuals. Further, ELISA showed that plasma HSP70 autoantibody level in CCA was significantly capable to discriminate CCA from healthy individuals with an area under the receiver operating characteristic curve of 0.9158 (cut-off 0.2630, 93.55% sensitivity and 73.91% specificity. Plasma levels of IgG autoantibodies against HSP70 were correlated with progression from healthy individuals to cholangitis to CCA (r = 0.679, P<0.001. In addition, circulating ENO1 and RNH1 autoantibodies levels were also significantly higher in cholangitis and CCA compared to healthy controls (P<0.05. Moreover, the combinations of HSP70, ENO1 or RNH1 autoantibodies positivity rates improved specificity to over 78%. In conclusion, plasma IgG autoantibodies against HSP70, ENO1 and RNH1 may represent new diagnostic markers for CCA.

  10. Ro52 autoantibodies arise from self-reactive progenitors in a mother of a child with neonatal lupus.

    Science.gov (United States)

    Reed, Joanne H; Gorny, Miroslaw K; Li, Liuzhe; Cardozo, Timothy; Buyon, Jill P; Clancy, Robert M

    2017-05-01

    The detection of cardiac conduction defects in an 18-24 week old foetus in the absence of structural abnormalities predicts with near certainty the presence of autoantibodies against 60kD and 52kD SSA/Ro in the mother regardless of her health status. Previous studies have emphasized these autoantibodies as key mediators of tissue injury. The aim of this study was to focus on the anti-Ro52 response to determine whether these autoantibodies originate from progenitors that are inherently self-reactive or from B-cells that acquire self-reactivity during an immune response. We traced the evolution of two anti-Ro52 autoantibodies isolated from circulating IgG1-switched B-cells from an asymptomatic mother of a child with third degree congenital heart block. The autoantibodies were expressed as their immune form and as pre-immune ancestors by reverting somatic mutations to germline sequence. The reactivity of pre-immune and immune antibodies for Ro52, Ro60, La and DNA was measured. Both anti-Ro52 autoantibodies exhibited a low frequency of somatic mutations (3-4%) and utilised the same heavy and light chain genes but represented distinct clones based on differing complementarity determining region sequences. Pre- and post-immune antibodies showed specific binding to Ro52 with no measurable reactivity for other autoantigens. Ro52 binding was higher for immune antibodies compared to pre-immune counterparts demonstrating that autoreactivity was enhanced by affinity maturation. These data indicate that Ro52 reactivity is an intrinsic property of the germline antibody repertoire in a mother with a pathogenic antibody defined by cardiac injury in her offspring, and implies defects in both central and peripheral tolerance mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

    Directory of Open Access Journals (Sweden)

    Chaojun Hu

    Full Text Available Autoantibodies in cerebrospinal fluid (CSF from patients with neuropsychiatric systemic lupus erythematosus (NPSLE may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosuspatients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43.Anti-proliferating cell nuclear antigen (PCNA was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A. The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045.Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009. Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

  12. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

    Directory of Open Access Journals (Sweden)

    Chan Koon H

    2010-09-01

    Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

  13. Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum Autoantibodies and Inflammatory Mediators

    Science.gov (United States)

    Baghdadi, Hussam; Abdel-Aziz, Nada; Ahmed, Nagwa Sayed; Mahmoud, Hany Salah; Barghash, Ayman; Nasrat, Abdullah; Nabo, Manal Mohamed Helmy; El Sayed, Salah Mohamed

    2015-01-01

    Autoimmune diseases have common properties characterized by abnormal blood chemistry with high serum autoimmune antibodies, and inflammatory mediators. Those causative pathological substances (CPS) cannot be excreted by physiological mechanisms. Current treatments for autoimmune diseases involve steroids, cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases having different etiology and pathogenesis via a pressure-dependent and size-dependent non-specific filtration then excretion of CPS causing clearance of blood and interstitial fluids. Al-hijamah clears blood passing through the fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an excellent treatment for rheumatoid arthritis that improved patients’ blood chemistry and induced significant clinical improvement and pharmacological potentiation. Al-hijamah improved the natural immunity and suppressed the pathological immunity through decreasing the serum level of autoantibodies, inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al-hijamah reduced significantly pain severity, number of swollen joints and disease activity with no significant side effects. Main steps of Al-hijamah are skin suction (cupping), scarification (sharatmihjam in Arabic) and second suction (triple S technique) that is better therapeutically than the traditional WCT (double S technique). Whenever an excess noxious substance is to be removed from patients’ blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam is a curative treatment in prophetic teachings according to the prophetic hadeeth: “Cure is in three: in shartatmihjam, oral honey and cauterization. I do not recommend my nation to cauterize”. Al-hijamah may have better therapeutic benefits than plasmapheresis. Al-hijamah may be

  14. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin

    2011-01-01

    Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS-associated au......Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS......-associated autoantibodies. Objective: To investigate whether BAFF levels are associated with disease severity/activity in untreated MS patients, and to assess the effect of IFN-beta therapy on circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels. Results: Twenty-three patients with relapsing......-remitting MS (RRMS) were followed longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF correlated positively at baseline with the expanded disability status scale (p

  15. Ro/SSA autoantibody-positive pregnancy: reactions to serial fetal Doppler echocardiographic surveillance.

    Science.gov (United States)

    Tingström, J; Hjelmstedt, A; Welin Henriksson, E; Sonesson, S-E; Wahren-Herlenius, M

    2015-12-01

    The risk for congenital heart block (CHB) associated with maternal Ro/SSA autoantibodies is low, but the possibility of treating early stages of disease has seen the introduction of Doppler echocardiographic surveillance programs with serial examinations during the CHB susceptibility weeks of pregnancy. The aim of the present study was to understand how Ro/SSA autoantibody-positive women having undergone Doppler echocardiographic surveillance programs and giving birth to children without CHB experienced their pregnancy and frequent ultrasound examinations. A validated questionnaire based on data from an interview-study was distributed to Ro/SSA-positive women supervised with Doppler examinations during their pregnancy (n = 100). The response rate was 79%. The majority of the women (61%) reported that the increased number of ultrasound examinations influenced their pregnancy, but in a positive way, with qualified information and additional support from health care personnel in conjunction with the examinations. Further, the visits to the clinic provided opportunities to see the ultrasound picture of the expected infant. However, one-third of the women also reported stress in relation to the examinations. Fetal echocardiographic surveillance holds many and predominantly positive effects for Ro/SSA-positive women during pregnancy in addition to the medical advantages. © The Author(s) 2015.

  16. Quantification and evaluation of the role of antielastin autoantibodies in the emphysematous lung.

    LENUS (Irish Health Repository)

    Low, Teck Boon

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) may be an autoimmune disease. Smoking causes an imbalance of proteases and antiproteases in the lung resulting in the generation of elastin peptides that can potentially act as autoantigens. Similar to COPD, Z alpha-1 antitrypsin deficiency (Z-A1ATD) and cystic fibrosis (CF) are associated with impaired pulmonary antiprotease defences leading to unopposed protease activity. Here, we show that there is a trend towards higher bronchoalveolar lavage fluid (BALF) antielastin antibody levels in COPD and Z-A1ATD and significantly lower levels in CF compared to control BALF; the lower levels in CF are due to the degradation of these antibodies by neutrophil elastase. We also provide evidence that these autoantibodies have the potential to induce T cell proliferation in the emphysematous lung. This study highlights that antielastin antibodies are tissue specific, can be detected at elevated levels in COPD and Z-A1ATD BALF despite their being no differences in their levels in plasma compared to controls, and suggests a therapeutic role for agents targeting these autoantibodies in the lungs.

  17. Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK).

    Science.gov (United States)

    Braus, B K; Miller, I; Kummer, S; Kleinwort, K J H; Hirmer, S; Hauck, S M; McMullen, R J; Kerschbaumer, M; Deeg, C A

    2017-05-01

    Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in horses causing intermittent ocular pain, eventually resulting in visual impairment. Affected horses typically respond to immunomodulatory treatment. However, the underlying cause of the disease remains enigmatic. The current study was undertaken to investigate the presence of autoantibodies in horses with immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls screening for serum autoantibodies against the corneal proteome using indirect immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis (2DE) with subsequent western blot analysis was performed followed by mass spectrometric identification of bands or spots of interest. Indirect immunofluorescence did not reveal a difference in immune response towards corneal proteins between healthy horses and those with IMMK. Using western blot analysis some horses affected by IMMK (4/28) showed a single band (1D) or a single spot (2DE) (5/28) not detected in healthy controls. The corresponding spot was identified as maspin (SERPINB5), a protein responsible for the inhibition of corneal vascularisation, cell migration and cell adhesion to the extracellular matrix. Tests with a recombinant human protein commercially available did not verify blot findings, but the human protein may not be fully cross-reactive. Still, maspin might play a role in some cases of equine IMMK. Further research is needed to clarify the etiology of this disease. Copyright © 2017. Published by Elsevier B.V.

  18. IA-2 autoantibody affinity in children at risk for type 1 diabetes.

    Science.gov (United States)

    Krause, Stephanie; Chmiel, Ruth; Bonifacio, Ezio; Scholz, Marlon; Powell, Michael; Furmaniak, Jadwiga; Rees Smith, Bernard; Ziegler, Anette-G; Achenbach, Peter

    2012-12-01

    Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 10(7) to 10(11)L/mol and was high (>1.0×10(9)L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis.

    Science.gov (United States)

    Caster, Dawn J; Korte, Erik A; Merchant, Michael L; Klein, Jon B; Wilkey, Daniel W; Rovin, Brad H; Birmingham, Dan J; Harley, John B; Cobb, Beth L; Namjou, Bahram; McLeish, Kenneth R; Powell, David W

    2015-12-01

    Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36 and 50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

    Directory of Open Access Journals (Sweden)

    Suk Chon

    2011-02-01

    Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

  1. [Autoantibody profile among Kaingang and Guarani tribe Indians in Southern Brazil].

    Science.gov (United States)

    Utiyama, S R; Guardiano, J; Petzl-Erler, M L; Mocelim, V; de Messias-Reason, I J

    2000-06-01

    This study investigated the autoantibody profile of 241 blood samples from 176 Kaingang and 65 Guarani Indians from three populations living on the Rio das Cobras and Ivaí reservations, in the state of Paraná, in southern Brazil. The presence of antimitochondrial, anti-smooth muscle, antinuclear, anti-parietal cell, and anti-liver-kidney microsome antibodies was determined by indirect immunofluorescence. These results were compared with samples from 100 healthy Caucasian individuals from the general population of the state. Total positivity was 9% for the indigenous population and 4% for the control population. The prevalence of anti-smooth muscle antibodies was significantly higher among the Guarani and Kaingang individuals from the Rio das Cobras reservation (P = 0.03). It is likely that the increased exposure that these indigenous Brazilians have to infectious diseases that were previously unknown to them comes from more contact with non-native populations, growing acculturation, and cultural practices that include scarification and tattooing. The presence of auto-antibodies in these Brazilian Indians may be related to mechanisms of molecular mimicry with viral or bacterial antigens.

  2. Idiopathic Inflammatory Myopathies; Association with Overlap Myositis and Syndromes: Classification, Clinical Characteristics, and Associated Autoantibodies

    Directory of Open Access Journals (Sweden)

    Pari Basharat

    2016-07-01

    Full Text Available Idiopathic inflammatory myopathies (IIM are traditionally identified as a group of disorders that target skeletal muscle due to autoimmune dysfunction. The IIM can be divided into subtypes based on certain clinical characteristics, and several classification schemes have been proposed. The predominant diagnostic criteria for IIM is the Bohan and Peter criteria, which subdivides IIM into primary polymyositis (PM, primary dermatomyositis (DM, myositis with another connective tissue disease, and myositis associated with cancer. However, this measure has been criticised for several reasons including lack of specific criteria to help distinguish between muscle biopsy findings of PM, DM, and immune-mediated necrotising myopathy, as well as the lack of identification of cases of overlap myositis (OM. Because of this issue, other classification criteria for IIM have been proposed, which include utilising myositis-associated antibodies and myositis-specific antibodies, as well as overlap features such as Raynaud’s phenomenon, polyarthritis, oesophageal abnormalities, interstitial lung disease, small bowel abnormalities such as hypomotility and malabsorption, and renal crises, amongst others. Indeed, the identification of autoantibodies associated with certain clinical phenotypes of myositis, in particular connective tissue disease-myositis overlap, has further helped divide IIM into distinct clinical subsets, which include OM and overlap syndromes (OS. This paper reviews the concepts of OM and OS as they pertain to IIM, including definitions in the literature, clinical characteristics, and overlap autoantibodies.

  3. Prevalence of IgG Autoantibodies against GD3 Ganglioside in Acute Zika Virus Infection

    Science.gov (United States)

    Nico, Dirlei; Conde, Luciana; Rivera-Correa, Juan L.; Vasconcelos-dos-Santos, Andréia; Mesentier-Louro, Louise; Freire-de-Lima, Leonardo; Arruda, Mônica Barcellos; Freire-de-Lima, Celio Geraldo; Ferreira, Orlando da Costa; Lopes Moreira, Maria Elisabeth; Zin, Andrea Araújo; Vasconcelos, Zilton Farias Meira; Otero, Rosalia Mendez; Palatnik-de-Sousa, Clarisa Beatriz; Tanuri, Amilcar; Todeschini, Adriane Regina; Savino, Wilson; Rodriguez, Ana; Morrot, Alexandre

    2018-01-01

    Zika virus (ZIKV) disease has become a global health emergency with devastating effects on public health. Recent evidences implicate the virus as an emergent neuropathological agent promoting serious pathologies of the human nervous system, that include destructive and malformation consequences such as development of ocular and fetal brain lesions, microcephaly in neonates, and Guillain–Barré syndrome (GBS) in adults. These neurological disorders of both central and peripheral nervous systems are thought to be associated to the neurotropic properties of the virus that has ability to infect neural stem cells as well as peripheral neurons, a hallmark of its pathogenicity. The presence of autoantibodies against gangliosides plays a pivotal role in the etiogenesis of GBS and a variety of neurological disorders. Gangliosides are a class of galactose-containing cerebrosides mainly expressed in nervous system tissues playing a critical role in the physiology of neural cells and neurogenesis. Herein, our findings indicate that patients at acute phase of ZIKV infection without any neurological signs show increased levels of IgG autoantibody against GD3 gangliosides, a class of glycolipid found to be highly expressed in neural stem cell acting in the maintenance of their self-renewal cellular capacity. It is possible that a pathological threshold of these antibodies is only acquired in secondary or subsequent infections. In the light of these evidences, we propose that the target of GD3 by autoimmune responses may possibly has an effect in the neuropathy and neurogenesis disorder seen during ZIKV infection. PMID:29594116

  4. Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

    DEFF Research Database (Denmark)

    Achenbach, P; Bonifacio, E; Williams, A J K

    2008-01-01

    -positive participants (median age 12.1 years; 57% male), 113 developed diabetes (5 year cumulative risk 56%), and 148 were also GADA-positive and IAA-positive (4Ab-positive). IA2betaA were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2beta......AIMS/HYPOTHESIS: The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2beta (IA2betaA) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial....... METHODS: Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2betaA. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. RESULTS: Of 212 ICA/IA2A...

  5. Acute-onset chronic inflammatory demyelinating polyneuropathy with cranial nerve involvement, dysautonomia, respiratory failure, and autoantibodies.

    Science.gov (United States)

    Hantson, Philippe; Kevers, Luc; Fabien, Nicole; Van Den Bergh, Peter

    2010-03-01

    We examined a 27-year-old woman who developed rapidly progressive quadriplegia and acute respiratory failure that required mechanical ventilation in the intensive care unit. It was unclear whether this was a presentation of Guillain-Barré syndrome (GBS) or acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). Remarkable features included multiple cranial nerve involvement, respiratory failure, dysautonomia, and skin manifestations. Several autoantibodies were elevated, including antinuclear (ANA), anticardiolipin (aCL), thyroid, and calcium-sensing receptor (CaSR) autoantibodies. The patient was initially diagnosed with GBS and treated with intravenous immunoglobulin (IVIg). After almost complete recovery, relapse with quadriplegia and respiratory failure was observed 12 weeks after motor symptom onset. She then received IVIg and steroid pulse therapy followed by maintenance oral methylprednisolone and plasma exchange. She recovered completely 4 months after the relapse. The further clinical and serological course was consistent with systemic lupus erythematosus (SLE)-associated CIDP. Herein we evaluate the association between A-CIDP and some biological markers of autoimmunity.

  6. Significance of combined determination of multiple autoantibodies in patients with systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Tao Hongqun; Li Xiaolong; Gong Jianguang; Wen Huaikai

    2006-01-01

    Objective: To explore the roles played by autoantibodies in systemic lupus erythematosus. Methods: Serum anti-dsDNA antibody (with RIA) and serum anti-nucleosome antibody (AnuA), AHA, anti SmD1-, anti Ro60UD-, anti U1 -RNP- , anti-Ro52KD, anti-SSB antibodies (with anti-nucleo antibodies linear spectrum blotting method) were detected in 50 patients with clinically proven systemic lupus erythematosus. Results: The positive rate with anti-SmD1 antibody was highest (82%), followed by anti-Ro60KD antibody (80%) and AnuA (72%). Positive rate with anti dsDNA-, AHA, anti-U1-RNP-, anti- Ro52KD and anti SSB-antibodies was 44%, 32%, 58%, 48% and 24% respectively. Positive rate with anti-SC1-70, ACA and Jo-1 antibodies was extremely low (below 10%). Conclusion: Multiple auto-antibodies were present in serum of patients with systemic lupus erythematosus and combined detection of them would improve the diagnostic sensitivity. (authors)

  7. Extraordinarily adaptive properties of the genetically encoded amino acids.

    Science.gov (United States)

    Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves, H James

    2015-03-24

    Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or "chemistry space." Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set.

  8. Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids

    Science.gov (United States)

    Ilardo, Melissa; Meringer, Markus; Freeland, Stephen; Rasulev, Bakhtiyor; Cleaves II, H. James

    2015-01-01

    Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set. PMID:25802223

  9. Encoding and Decoding Models in Cognitive Electrophysiology.

    Science.gov (United States)

    Holdgraf, Christopher R; Rieger, Jochem W; Micheli, Cristiano; Martin, Stephanie; Knight, Robert T; Theunissen, Frederic E

    2017-01-01

    Cognitive neuroscience has seen rapid growth in the size and complexity of data recorded from the human brain as well as in the computational tools available to analyze this data. This data explosion has resulted in an increased use of multivariate, model-based methods for asking neuroscience questions, allowing scientists to investigate multiple hypotheses with a single dataset, to use complex, time-varying stimuli, and to study the human brain under more naturalistic conditions. These tools come in the form of "Encoding" models, in which stimulus features are used to model brain activity, and "Decoding" models, in which neural features are used to generated a stimulus output. Here we review the current state of encoding and decoding models in cognitive electrophysiology and provide a practical guide toward conducting experiments and analyses in this emerging field. Our examples focus on using linear models in the study of human language and audition. We show how to calculate auditory receptive fields from natural sounds as well as how to decode neural recordings to predict speech. The paper aims to be a useful tutorial to these approaches, and a practical introduction to using machine learning and applied statistics to build models of neural activity. The data analytic approaches we discuss may also be applied to other sensory modalities, motor systems, and cognitive systems, and we cover some examples in these areas. In addition, a collection of Jupyter notebooks is publicly available as a complement to the material covered in this paper, providing code examples and tutorials for predictive modeling in python. The aim is to provide a practical understanding of predictive modeling of human brain data and to propose best-practices in conducting these analyses.

  10. Engineering Genetically Encoded FRET Sensors

    Science.gov (United States)

    Lindenburg, Laurens; Merkx, Maarten

    2014-01-01

    Förster Resonance Energy Transfer (FRET) between two fluorescent proteins can be exploited to create fully genetically encoded and thus subcellularly targetable sensors. FRET sensors report changes in energy transfer between a donor and an acceptor fluorescent protein that occur when an attached sensor domain undergoes a change in conformation in response to ligand binding. The design of sensitive FRET sensors remains challenging as there are few generally applicable design rules and each sensor must be optimized anew. In this review we discuss various strategies that address this shortcoming, including rational design approaches that exploit self-associating fluorescent domains and the directed evolution of FRET sensors using high-throughput screening. PMID:24991940

  11. A SSVEP Stimuli Encoding Method Using Trinary Frequency-Shift Keying Encoded SSVEP (TFSK-SSVEP

    Directory of Open Access Journals (Sweden)

    Xing Zhao

    2017-06-01

    Full Text Available SSVEP is a kind of BCI technology with advantage of high information transfer rate. However, due to its nature, frequencies could be used as stimuli are scarce. To solve such problem, a stimuli encoding method which encodes SSVEP signal using Frequency Shift–Keying (FSK method is developed. In this method, each stimulus is controlled by a FSK signal which contains three different frequencies that represent “Bit 0,” “Bit 1” and “Bit 2” respectively. Different to common BFSK in digital communication, “Bit 0” and “Bit 1” composited the unique identifier of stimuli in binary bit stream form, while “Bit 2” indicates the ending of a stimuli encoding. EEG signal is acquired on channel Oz, O1, O2, Pz, P3, and P4, using ADS1299 at the sample rate of 250 SPS. Before original EEG signal is quadrature demodulated, it is detrended and then band-pass filtered using FFT-based FIR filtering to remove interference. Valid peak of the processed signal is acquired by calculating its derivative and converted into bit stream using window method. Theoretically, this coding method could implement at least 2n−1 (n is the length of bit command stimulus while keeping the ITR the same. This method is suitable to implement stimuli on a monitor and where the frequency and phase could be used to code stimuli is limited as well as implementing portable BCI devices which is not capable of performing complex calculations.

  12. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients

    Science.gov (United States)

    Cho, Michael Jeffrey; Lo, Agnes S.Y.; Mao, Xuming; Nagler, Arielle R.; Ellebrecht, Christoph T.; Mukherjee, Eric M.; Hammers, Christoph M.; Choi, Eun-Jung; Sharma, Preety M.; Uduman, Mohamed; Li, Hong; Rux, Ann H.; Farber, Sara A.; Rubin, Courtney B.; Kleinstein, Steven H.; Sachais, Bruce S.; Posner, Marshall R.; Cavacini, Lisa A.; Payne, Aimee S.

    2014-01-01

    Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies from four PV patients and identify pathogenic VH1-46 autoantibodies from all four patients. Unexpectedly, VH1-46 autoantibodies had relatively few replacement mutations. We reverted antibody somatic mutations to their germline sequences to determine the requirement of mutations for autoreactivity. Three of five VH1-46 germline-reverted antibodies maintain Dsg3 binding, compared to zero of five non-VH1-46 germline-reverted antibodies. Site-directed mutagenesis of VH1-46 antibodies demonstrate that acidic amino acid residues introduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our data suggest that VH1-46 autoantibody gene usage is commonly found in PV because VH1-46 antibodies require few to no mutations to acquire Dsg3 autoreactivity, which may favor their early selection. Common VH gene usage indicates common humoral immune responses, even among unrelated patients. PMID:24942562

  13. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette

    2006-01-01

    The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients...

  14. Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals

    NARCIS (Netherlands)

    Maijer, Karen I.; Neumann, Elena; Müller-Ladner, Ulf; Drop, Daniël A. C. A. D.; Ramwadhdoebe, Tamara H.; Choi, Ivy Y. K.; Gerlag, Daniëlle M.; de Hair, Maria J. H.; Tak, Paul P.

    2015-01-01

    We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and

  15. Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

    NARCIS (Netherlands)

    van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.

    2007-01-01

    Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,

  16. Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale.

    Science.gov (United States)

    Ponomarenko, Natalia A; Durova, Oxana M; Vorobiev, Ivan I; Belogurov, Alexey A; Telegin, Georgy B; Suchkov, Sergey V; Misikov, Victor K; Morse, Herbert C; Gabibov, Alexander G

    2006-02-28

    Autoantibodies toward myelin basic protein (MBP) evidently emerge in sera and cerebrospinal fluid of the patients with multiple sclerosis (MS), as well as in a MS rodent model, i.e., experimental autoimmune encephalomyelitis (EAE). The studies of the last two decades have unveiled somewhat controversial data on the diagnostic applicability of anti-MBP autoantibodies as a disease' marker. Here, we present the results of new functional analysis of the anti-MBP autoantibodies isolated from MS (in patients) and EAE (in mice) sera, based on their proteolytic activity against the targeted autoantigen. The activity was shown to be the intrinsic property of the IgG molecule. No activity was found in the sera-derived antibody fraction of healthy donors and control mice. Sera of 24 patients with clinically proven MS at different stages of the disease, and 20 healthy controls were screened for the anti-MBP antibody-mediated proteolytic activity. The activity correlated with the scores on the MS expanded disability status scale (EDSS) (r(2)=0.85, P<0.001). Thus, the anti-MBP autoantibody-mediated proteolysis may be regarded as an additional marker of the disease progression.

  17. Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies

    NARCIS (Netherlands)

    Meulenbroek, Elisabeth M.; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S.; Wouters, Diana

    2015-01-01

    In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the

  18. Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency

    DEFF Research Database (Denmark)

    Pedersen, I.B.; Knudsen, N.; Jorgensen, T.

    2003-01-01

    BACKGROUND AND AIMS Autoimmune thyroiditis is one of the most common autoimmune disorders. Autoantibodies against the thyroid gland, with thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) as the most common autoantibodies, can often be demonstrated in serum in population...... prevalence rate of thyroid autoantibodies (TPO-Ab and/or Tg-Ab) was 18.8%. The prevalence rates of TPO-Ab and Tg-Ab were similar (13.1 vs. 13.0%). Both antibodies were more frequent in females than in males, and in females the prevalence rates increased with age. In the age group 60-65 years thyroid...... antibodies were more frequently measured in sera from moderate than from mild iodine-deficient area (P = 0.02), whereas no differences were seen in younger subjects. In 38.8% of participants with thyroid autoantibodies in serum, both antibodies were present. In sera with both TPO-Ab and Tg-Ab present...

  19. Aire deficient mice do not develop the same profile of tissue-specific autoantibodies as APECED patients.

    Science.gov (United States)

    Pöntynen, Nora; Miettinen, Aaro; Arstila, T Petteri; Kämpe, Olle; Alimohammadi, Mohammad; Vaarala, Outi; Peltonen, Leena; Ulmanen, Ismo

    2006-09-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, or APS1), is a monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. The three main components of APECED are chronic mucocuteaneous candidiasis, hypoparathyroidism and adrenocortical insufficiency. However, several additional endocrine or other autoimmune disease components, or ectodermal dystrophies form the individually variable clinical picture of APECED. An important feature of APECED is a spectrum of well-characterized circulating autoantibodies, reacting against tissue-specific autoantigens. Aire deficient mice develop some characteristics of APECED phenotype. In order to investigate whether the Aire deficient mice produce autoantibodies similar to human APECED, we studied the reactivity of Aire mouse sera against mouse homologues of 11 human APECED antigens. None of the APECED antigens indicated elevated reactivity in the Aire knock-out mouse sera, implying the absence of APECED associated autoantibodies in Aire deficient mice. These findings were supported by the failure of the autoantigens to activate mouse T-cells. Furthermore, Aire knock-out mice did not express increased levels of anti-nuclear antibodies compared to wt mice. This study indicates that spontaneous induction of tissue-specific autoantibodies similar to APECED does not occur in the rodent model suggesting differences in the immunopathogenic mechanisms between mice and men. Copyright 2006 Elsevier Ltd.

  20. Induction of anti-β2 -glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes

    NARCIS (Netherlands)

    van O S, G. M. A.; Meijers, J. C. M.; Agar, Ç; Valls Seron, M.; Marquart, J. A.; Åkesson, P.; Urbanus, R. T.; Derksen, R. H. W. M.; Herwald, H.; Mörgelin, M.; D E Groot, P. G.

    2011-01-01

    The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti-β(2) -glycoprotein I (β(2) -GPI) autoantibodies. β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook conformation after binding to phospholipids. Only the

  1. An improved flow cytometric immunobead array to detect autoantibodies in plasma from patients with immune thrombocytopenic purpura.

    Science.gov (United States)

    Zhao, Yunxiao; Zhu, Mingqing; Jiang, Miao; Zuo, Bin; Wu, Qingyu; Ruan, Changgeng; He, Yang

    2015-01-01

    Autoantibodies against platelet glycoproteins (GPs) play an important role in immune thrombocytopenic purpura (ITP). This study was to develop an improved flow cytometric immunobead array (FCIA) assay to detect platelet autoantibodies in ITP patient plasma. Plasma samples were isolated from 71 ITP patients and 136 non-ITP controls and incubated with platelets from normal individuals. After washing, platelets were lysed and the platelet lysates were incubated with polystyrene microbeads coupled with monoclonal antibodies against human GPs IX (SZ1), Ib (SZ2), IIIa (SZ21), IIb (SZ22), and P-selectin (SZ51). Platelet GP-autoantibody complexes were detected by flow cytometry using a FITC-labeled secondary antibody. Autoantibodies against platelet GPIb, GPIIb, GPIIIa, GPIX and P-selectin were detected in plasma from ITP patients, as indicated by high mean fluorescent intensity values when microbeads with antibodies SZ1, SZ2, SZ21, SZ22, and SZ51 were used. In ROC analysis, values of the area under the curve were 0.74, 0.83, 0.80, 0.79 and 0.87, respectively. Compared with the previously reported assays, this new FCIA eliminated the need of isolating platelets from ITP patients without compromising assay sensitivity and accuracy in predicting ITP. This simplified FICA assay may be more suitable for ITP diagnosis in clinical laboratory settings. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis

    Science.gov (United States)

    Peschl, Patrick; Ramberger, Melanie; Höftberger, Romana; Jöhrer, Karin; Baumann, Matthias; Rostásy, Kevin; Reindl, Markus

    2017-01-01

    Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers. PMID:28327523

  3. Clinical and immunological aspects of anti-peptidylarginine deiminase type 4 (anti-PAD4) autoantibodies in rheumatoid arthritis.

    Science.gov (United States)

    Reyes-Castillo, Zyanya; Muñoz-Valle, José Francisco; Llamas-Covarrubias, Mara A

    2018-02-01

    Rheumatoid arthritis (RA) is the most common rheumatic autoimmune disease worldwide, which causes progressive joint damage and can lead to functional disability. Despite prominent advances in RA diagnosis and treatment during the last 20years, there is still a need for novel biomarkers that aid in diagnosis and prognosis of this heterogeneous disease. Citrullination is a key post-translational modification implicated on anti-citrullinated protein/peptide antibodies (ACPA) production in RA, catalyzed by human peptidylarginine deiminases (PADs). Among these enzymes, PAD4 has been recognized as an important player in RA pathogenesis and the enzyme itself is a target of autoantibodies (anti-PAD4) in a subgroup of RA patients. Accumulating evidence suggests that anti-PAD4 autoantibodies may be useful as a severity biomarker in RA and recent studies have also shed light on the functional significance of these autoantibodies. This review summarizes the evidence on anti-PAD4 autoantibodies in RA, and addresses its usefulness for disease diagnosis and prognosis. Novel immunological aspects of anti-PAD4 antibodies and their relevance to RA pathogenesis are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Longitudinal Tracking of Autoantibody Levels in a Pemphigus Vulgaris Patient: Support for a Role of Anti-Desmoglein 1 Autoantibodies as Predictors of Disease Progression.

    Science.gov (United States)

    Abidi, Nadia Y; Lainiotis, Irene; Malikowski, Gretchen; Seiffert-Sinha, Kristina; Sinha, Animesh A

    2017-02-01

    Anti-desmoglein (Dsg) 1 and -Dsg3 antibody titers have an established role in the diagnosis of the autoimmune blistering skin disease pemphigus vulgaris (PV). However, their usefulness for disease monitoring has been controversial. A recent large-scale immunoprofiling study by our group indicated that anti-Dsg1 levels may be a better predictor of disease activity than anti-Dsg3 levels, with declining levels predicting progression from active phase of disease to early remission, irrespective of lesional subtypes. Here, we report an illustrative case of a PV patient with mucocutaneous disease that was followed longitudinally for >2.5 years clinically and by serum serology. Autoantibody levels directed against both Dsg1 and -3 showed a moderate correlation with PDAI scores, supporting a correlation of Dsg1 and 3 levels with disease severity. However, while both anti-Dsg3 and -Dsg1 antibody levels demonstrated a steady parallel decline after initiation of rituximab therapy, only anti-Dsg1 antibodies fell to levels below detectability with the progression to remission, while anti-Dsg3 levels remained elevated. This case illustrates the potential key role and clinical benefit of tracking anti-Dsg1 levels to monitor and conceivably predict disease activity in patients with PV. J Drugs Dermatol. 2017;16(2):135-139..

  5. Macroamylasemia attributable to gluten-related amylase autoantibodies: a case report.

    Science.gov (United States)

    Barera, G; Bazzigaluppi, E; Viscardi, M; Renzetti, F; Bianchi, C; Chiumello, G; Bosi, E

    2001-06-01

    . Screening for other autoantibodies-including antinuclear, islet cell, glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen 512, adrenal gland, and cytoplasmic neutrophil granulocyte antibodies-was negative. A diagnosis of CD, MA, and hypothyroidism attributable to autoimmune thyroiditis was made. A gluten-free diet and oral replacement with L-thyroxine was started with clinical improvement. Serum amylase and amylase clearance/creatinine clearance ratio normalized, consistent with resolution of MA. The patient's serum samples were obtained at the time of CD diagnosis and at 3 and 12 months after instituting a gluten-free diet. Serum samples from 10 consecutive untreated celiac children were disease controls, and 39 participants with no gastrointestinal symptoms and no family history of CD served as healthy controls. The origin of MA as determined by complexes of amylase with circulating immunoglobulins was tested by the measurement of amylase on supernatants after precipitation of immune complexes with either protein A Sepharose or polyethylene glycol. The precipitation of >60% of amylase activity was consistent with the presence of MA. Immunoglobulin G (IgG) and immunoglobulin A (IgA) circulating autoantibodies to amylase were measured using recently developed enzyme-linked immunosorbent assay (ELISA), using porcine amylase as antigen. Results were expressed as arbitrary units (AUs). Statistical analysis was performed by Student's t test for unpaired data. IgA and IgG antibodies to exocrine pancreas tissue were detected by indirect immunofluorescence on human pancreas cryosections. Serum immunoprecipitation with either protein A Sepharose or polyethylene glycol reduced amylase activity from 1698 to 89 U/L (94.8%) and to 75 U/L (95.6%), with only marginal reduction in control serum samples. The ELISA for autoantibodies to amylase detected high values, both IgA (3531 AU) and IgG (1855 AU), in the serum sample from the patient at CD diagnosis. Ig

  6. SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

    Science.gov (United States)

    Hitz, Benjamin C; Rowe, Laurence D; Podduturi, Nikhil R; Glick, David I; Baymuradov, Ulugbek K; Malladi, Venkat S; Chan, Esther T; Davidson, Jean M; Gabdank, Idan; Narayana, Aditi K; Onate, Kathrina C; Hilton, Jason; Ho, Marcus C; Lee, Brian T; Miyasato, Stuart R; Dreszer, Timothy R; Sloan, Cricket A; Strattan, J Seth; Tanaka, Forrest Y; Hong, Eurie L; Cherry, J Michael

    2017-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package.

  7. SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

    Directory of Open Access Journals (Sweden)

    Benjamin C Hitz

    Full Text Available The Encyclopedia of DNA elements (ENCODE project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data has been released as a separate Python package.

  8. Optimized purification strategies for the elimination of non-specific products in the isolation of GAD65-specific monoclonal autoantibodies [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    2016-04-01

    Full Text Available Autoantibodies against antigens expressed by insulin-producing β cells are circulating in both healthy individuals and patients at risk of developing Type 1 diabetes. Recent studies suggest that another set of antibodies (anti-idiotypic antibodies exists in this antibody/antigen interacting network to regulate auto-reactive responses. Anti-idiotypic antibodies may block the antigen-binding site of autoantibodies or inhibit autoantibody expression and secretion. The equilibrium between autoantibodies and anti-idiotypic antibodies plays a critical role in mediating or preventing autoimmunity. In order to investigate the molecular mechanisms underlying such a network in autoimmunity and potentially develop neutralizing reagents to prevent or treat Type 1 diabetes, we need to produce autoantibodies and autoantigens with high quality and purity. Herein, using GAD65/anti-GAD65 autoantibodies as a model system, we aimed to establish reliable approaches for the preparation of highly pure autoantibodies suitable for downstream investigation.

  9. Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study.

    Science.gov (United States)

    Long, Anna E; Wilson, Isabel V; Becker, Dorothy J; Libman, Ingrid M; Arena, Vincent C; Wong, F Susan; Steck, Andrea K; Rewers, Marian J; Yu, Liping; Achenbach, Peter; Casas, Rosaura; Ludvigsson, Johnny; Williams, Alistair J K; Gillespie, Kathleen M

    2018-03-12

    Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of 'slow progressors' (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years. Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Bart's Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed <5 years old from BOX) using the χ 2 test. In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele. No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.

  10. Optimal Achievable Encoding for Brain Machine Interface

    Science.gov (United States)

    2017-12-22

    AFRL-RH-WP-TP-2017-0001 Optimal Achievable Encoding for Brain- Machine Interface Eduardo Chichilnisky Leland Stanford Junior...Oct 2016 – 30 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Optimal Achievable Encoding for Brain- Machine Interface 5b...required. First, we developed novel models of retinal encoding that improve upon the state of the art, by using machine learning methods to

  11. The ENCODE project: missteps overshadowing a success.

    Science.gov (United States)

    Eddy, Sean R

    2013-04-08

    Two clichés of science journalism have now played out around the ENCODE project. ENCODE's publicity first presented a misleading "all the textbooks are wrong" narrative about noncoding human DNA. Now several critiques of ENCODE's narrative have been published, and one was so vitriolic that it fueled "undignified academic squabble" stories that focused on tone more than substance. Neither story line does justice to our actual understanding of genomes, to ENCODE's results, or to the role of big science in biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Encoder designed to work in harsh environments

    Energy Technology Data Exchange (ETDEWEB)

    Toop, L.

    2007-05-15

    Dynapar has developed the Acuro AX71 absolute encoder for use on offshore or land-based oil rig operations. It provides feedback on the operation of automated systems such as draw works, racking systems, rotary tables and top drives. By ensuring that automated systems function properly, this encoder responds to a need by the oil and gas industry to keep workers safe and improve efficiency, particularly for operations in rugged situations. The encoder provides feedback from motor systems to controllers, giving information about position and speed of downhole drill bits. This newly developed encoder is better than commonly used incremental encoders which are not precise in strong electrical noise environments. Rather, the absolute encoder uses a different method of reporting to the controller. A digital signal is transmitted constantly as the device operates. It is less susceptible to noise issues. It is highly accurate, tolerant of noise and is not affected by power outages. However, the absolute encoder is generally more delicate in drilling applications with high ambient temperatures and shock levels. Dynapar addressed this issue by developing compact stainless steel housing that is useful for corrosion resistance in marine applications. The AX71 absolute encoder can withstand up to 100 G of mechanical shock and ambient temperatures of up to 60 degrees C. The encoder is ATEX certified without barriers, and offers the high resolution feedback of 4,000 counts of multiturn rotation and 16,000 counts of position. 1 fig.

  13. Universal dynamic goniometer for rotary encoders

    Science.gov (United States)

    Smirnov, Nikolai V.; Latyev, Svjatoslav M.; Naumova, Anastasiia I.

    2017-06-01

    A novel dynamic goniometer for the accuracy of rotary encoders has been developed on the base of the method of comparison with the reference encoder. The set-up of the goniometer considers all constructive and informative characteristics of measured encoders. The novel goniometer construction uses the new compensating method of instrumental errors in automatic working process. The advantages of the dynamic goniometer in combination with an optical rotary encoder at the reduction of the measuring time and a simultaneous increase of the accuracy.

  14. Absence of high-affinity calreticulin autoantibodies in patients with systemic rheumatic diseases and coeliac disease

    DEFF Research Database (Denmark)

    Jørgensen, C S; Hansen, K B; Jacobsen, Søren

    2005-01-01

    Calreticulin has been reported to be an autoantigen in various autoimmune connective tissue diseases and in coeliac disease. Previous studies have used incubation buffers with low salt and low detergent concentrations (low stringency conditions) with serum albumin or other proteins as a blocking...... binding (high stringency conditions). Using the high stringency conditions, we screened sera from 107 patients with systemic lupus erythematosus, sera from patients with other systemic autoimmune diseases and from children with coeliac disease for the presence of high-affinity calreticulin autoantibodies...... by immunoblotting and ELISA. None of the sera contained high-affinity calreticulin antibodies. It is concluded that calreticulin is not a common autoantigen in patients with autoimmune connective tissue diseases or coeliac disease....

  15. Prevalence and predictive value of islet cell antibodies and insulin autoantibodies in women with gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P; Kühl, C; Buschard, K

    1994-01-01

    The objective of the present study was to investigate the predictive value of islet cell antibodies (ICA) and insulin autoantibodies (IAA) for development of diabetes in women with previous gestational diabetes (GDM). Two hundred and forty-one previous diet-treated GDM patients and 57 women without...... previous GDM were examined 2-11 years after the index pregnancy. In subgroups, plasma from the diagnostic OGTT during index pregnancy was analysed for ICA and IAA. Among the previous GDM patients, 3.7% had developed Type 1 diabetes and 13.7% Type 2 diabetes. Four (2.9%) of the 139 GDM patients tested...... for ICA were ICA-positive and three of these had Type 1 diabetes at follow-up, as well as three ICA-negative patients. The sensitivity, specificity, and predictive value of ICA-positivity for later development of diabetes were 50%, 99%, and 75%, respectively. None of the women was IAA-positive during...

  16. Staining Pattern Classification of Antinuclear Autoantibodies Based on Block Segmentation in Indirect Immunofluorescence Images

    Science.gov (United States)

    Li, Jiaqian; Tseng, Kuo-Kun; Hsieh, Zu Yi; Yang, Ching Wen; Huang, Huang-Nan

    2014-01-01

    Indirect immunofluorescence based on HEp-2 cell substrate is the most commonly used staining method for antinuclear autoantibodies associated with different types of autoimmune pathologies. The aim of this paper is to design an automatic system to identify the staining patterns based on block segmentation compared to the cell segmentation most used in previous research. Various feature descriptors and classifiers are tested and compared in the classification of the staining pattern of blocks and it is found that the technique of the combination of the local binary pattern and the k-nearest neighbor algorithm achieve the best performance. Relying on the results of block pattern classification, experiments on the whole images show that classifier fusion rules are able to identify the staining patterns of the whole well (specimen image) with a total accuracy of about 94.62%. PMID:25474260

  17. Proteomics Approaches to Identify Tumor Antigen Directed Autoantibodies as Cancer Biomarkers

    Directory of Open Access Journals (Sweden)

    Yuji Imafuku

    2004-01-01

    Full Text Available The identification of autoantibodies to tumor cell proteins by proteomics approaches has great potential impact on cancer biomarker discovery. The humoral immune response represents a form of biological amplification of signals that are otherwise weak due to very low concentrations of antigen, especially in the early stages of cancers. In addition, proteomics can detect immunoreactivity directed against protein post-translational modifications. Two-dimensional gel based Western blots, protein antigen microarrays, and multiplex ELISA reactions have been applied by our group to antigen based biomarker detection and validation. The latter two are based on liquid-phase separations that are suitable for automation. This work has resulted in the identification of numerous cancer biomarker candidates. Large clinical studies are currently planned to establish their value in early cancer diagnosis.

  18. Proteomics approaches to identify tumor antigen directed autoantibodies as cancer biomarkers.

    Science.gov (United States)

    Imafuku, Yuji; Omenn, Gilbert S; Hanash, Samir

    2004-01-01

    The identification of autoantibodies to tumor cell proteins by proteomics approaches has great potential impact on cancer biomarker discovery. The humoral immune response represents a form of biological amplification of signals that are otherwise weak due to very low concentrations of antigen, especially in the early stages of cancers. In addition, proteomics can detect immunoreactivity directed against protein post-translational modifications. Two-dimensional gel based Western blots, protein antigen microarrays, and multiplex ELISA reactions have been applied by our group to antigen based biomarker detection and validation. The latter two are based on liquid-phase separations that are suitable for automation. This work has resulted in the identification of numerous cancer biomarker candidates. Large clinical studies are currently planned to establish their value in early cancer diagnosis.

  19. Wegener's Granulomatosis: A Model of Auto-antibodies in Mucosal Autoimmunity

    Science.gov (United States)

    Kelley, James M.; Edberg, Jeffrey C.; Kimberly, Robert P.

    2009-01-01

    Wegener's granulomatosis (WG) is an autoimmune condition marked by vasculitis of small and medium sized vessels particularly affecting the upper respiratory tract and kidneys. There is a strong mucosal component similar to other autoimmune conditions such as systemic lupus erythematosus and Behçet's disease. While the pathogenesis of WG is not completely known, auto-antibodies such as IgG ANCAs have been implicated in endovascular damage and modulation of neutrophil / monocyte responses by Fc receptor (FcR) signaling. Due to the substantial mucosal involvement in WG (oral, nasal, and upper respiratory tract involvement), it is probable that IgA antibodies (perhaps IgA ANCAs) play a role in disease. Given discrepancies in associating ANCA levels with disease activity, future work should determine if IgA ANCAs are present in WG patients and examine the biology underlying the ANCAs' signaling partners - the FcRs. PMID:19482554

  20. No neuronal autoantibodies detected in plasma of patients with a bipolar I disorder.

    Science.gov (United States)

    Snijders, Gijsje; Titulaer, Maarten J; Bergink, Veerle; Bastiaansen, Anna E; Schreurs, Marco W J; Ophoff, Roel A; Boks, Marco P; Kahn, René S; de Witte, Lot D

    2018-01-01

    A subpopulation of patients with bipolar disorder type I (BD-I) might suffer from undiagnosed autoimmune encephalitis. We tested plasma of 104 BD-I patients with a current or recent manic episode in the past 2 years for the presence of neuronal autoantibodies using immunohistochemistry, immunocytochemistry and cell-based assay (CBA). Neuronal antibodies were not detected in any of the BD type I. This finding suggests that the frequency of an undiagnosed autoimmune encephalitis in patients with BD I is less than 1%. However, these findings need to be confirmed in cerebrospinal fluid and/or blood of acutely ill manic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Thyroid peroxidase and thyroglobulin auto-antibodies in patients with newly diagnosed overt hypothyroidism

    DEFF Research Database (Denmark)

    Carle, A.; Laurberg, P.; Knudsen, N.

    2006-01-01

    Objectives: Thyroid autoimmunity is a major cause for hypothyroidism. We describe thyroid auto-antibodies in patients with various nosological subtypes of hypothyroidism identified in a population study. Design: Population-based follow-up study identifying all new cases of hypothyroidism in an open...... cohort. Methods: We established a monitoring system, and identified all new cases with primary overt hypothyroidism (n = 685) in a 4 year period in a well-defined population cohort (2,027,208 person-years of observation). Patients were sub-classified into: spontaneous hypothyroidism, presumably...... of autoimmune origin ( n 578); non-spontaneous hypothyroidism ( associated with medication, delivery, neck-irradiation or subacute thyroiditis, n 97); and congenital hypothyroidism ( n 10). A total of 186 adult patients (61% of those invited) underwent thyroid ultrasonography and measurements of antibodies...

  2. Autoantibodies against complement components in systemic lupus erythematosus - role in the pathogenesis and clinical manifestations.

    Science.gov (United States)

    Hristova, M H; Stoyanova, V S

    2017-12-01

    Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common. These antibodies cause conformational changes leading to pathological activation or inhibition of complement with organ damage and/or limited capacity of the immune system to clear immune complexes and apoptotic debris. Finally, we summarize the role of complement antibodies in the pathogenesis of systemic lupus erythematosus and discuss the mechanism of some related clinical conditions such as infections, thyroiditis, thrombosis, acquired von Willebrand disease, etc.

  3. Epitope Fingerprinting for Recognition of the Polyclonal Serum Autoantibodies of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Luiz Carlos de Oliveira-Júnior

    2015-01-01

    Full Text Available Autoantibodies (aAb associated with Alzheimer’s disease (AD have not been sufficiently characterized and their exact involvement is undefined. The use of information technology and computerized analysis with phage display technology was used, in the present research, to map the epitope of putative self-antigens in AD patients. A 12-mer random peptide library, displayed on M13 phages, was screened using IgG from AD patients with two repetitions. Seventy-one peptides were isolated; however, only 10 were positive using the Elisa assay technique (Elisa Index > 1. The results showed that the epitope regions of the immunoreactive peptides, identified by phage display analysis, were on the exposed surfaces of the proteins. The putative antigens MAST1, Enah, MAO-A, X11/MINT1, HGF, SNX14, ARHGAP 11A, APC, and CENTG3, which have been associated with AD or have functions in neural tissue, may indicate possible therapeutic targets.

  4. Prevalence of anti-retinal autoantibodies in different stages of Age-related macular degeneration.

    Science.gov (United States)

    Adamus, Grazyna; Chew, Emily Y; Ferris, Frederick L; Klein, Michael L

    2014-12-08

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults. Anti-retinal autoantibodies (AAbs) have been found in individuals with AMD. The goal of the study was to determine the AAb specificity in different stages of AMD, and determine whether there is a prevalent AAb signature. Sera of 134 participants in the Age-related Eye Disease Study were analyzed for anti-retinal AAbs by western blotting. The subjects were classified by diagnostic subgroups based upon their clinical classification: No AMD, Intermediate AMD, and Late AMD - geographic atrophy (GA) and Late AMD - neovascular (NV). The presence of anti-retinal AAb was detected in 58% patients with Intermediate and Late AMD, and 54% of those with no AMD. AAbs bound to fifteen different retinal antigens. Most individuals had 1 specific AAbs (67%), with the remainder having 2 to 4 different AAbs. Over 40% of patients with Intermediate AMD, and 46% of those with GA had anti-enolase AAbs, compared with 29% of individuals with NV and 29% with no AMD. Different AAbs signatures related to NV as compared to GA and/or Intermediate AMD were distinguished. Anti-40-kDa (10%) and 42-kDa (16%) autoantibodies were associated with Intermediate AMD, while anti-30-kDa AAbs (23%) were primarily present in GA. Anti-32-kDa (12%), 35-kDa (21%), and 60-kDa (8%) AAbs were more frequent in NV AMD. A unique AAb pattern for each of the disease subgroups was present when AMD progressed from the intermediate to the late forms of severity. Differences in the frequency of specific AAbs between AMD subgroups suggested that they may participate in pathogenicity of AMD. Further studies are necessary to confirm these observations in the larger cohort and individual AMD patients over time.

  5. No evidence of circulating autoantibodies against osteoprotegerin in patients with celiac disease

    Science.gov (United States)

    Larussa, Tiziana; Suraci, Evelina; Nazionale, Immacolata; Leone, Isabella; Montalcini, Tiziana; Abenavoli, Ludovico; Imeneo, Maria; Pujia, Arturo; Luzza, Francesco

    2012-01-01

    AIM: To investigate risk factors for low bone mineral density (BMD) in celiac disease (CD) patients, focusing on circulating autoantibodies against osteoprotegerin (OPG). METHODS: Seventy asymptomatic CD adult patients on gluten-free diet (GFD) and harbouring persistent negative CD-related serology were recruited. Conventional risk factors for osteoporosis (e.g., age, sex, menopausal status, history of fractures, smoke, and body mass index) were checked and BMD was assessed by dual energy X ray absorptiometry. Serum calcium and parathyroid hormone (PTH) levels were evaluated. Thirty-eight patients underwent repeat duodenal biopsy. Serum samples from a selected sub-group of 30 patients, who were also typed for human leukocyte antigen (HLA) DQ2 and DQ8 haplotype, were incubated with homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after immunoprecipitation. RESULTS: Despite persistent negative CD-related serology and strict adherence to GFD, 49 out of the 70 (74%) patients displayed low BMD. Among these patients, 13 (24%) showed osteoporosis and 36 (76%) osteopenia. With the exception of age, conventional risk factors for osteoporosis did not differ between patients with normal and low BMD. Circulating serum calcium and PTH levels were normal in all patients. Duodenal mucosa healing was found in 31 (82%) out of 38 patients who underwent repeat duodenal biopsy with 20 (64%) still displaying low BMD. The remaining 7 patients had an incomplete normalization of duodenal mucosa with 6 (84%) showing low BMD. No evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for, independent of BMD, duodenal histology, and HLA status. CONCLUSION: If any, the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one. PMID:22529691

  6. Post-streptococcal auto-antibodies inhibit protein disulfide isomerase and are associated with insulin resistance.

    Directory of Open Access Journals (Sweden)

    Adi Aran

    2010-09-01

    Full Text Available Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33% and without (67% markers of recent streptococcal infections [anti-Streptolysin O (ASLO or anti-DNAse B (ADB]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI, an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61 and PDI (P328-338. The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001. Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001, and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039 and insulin resistance (Homeostatic Model Assessment (HOMA 4.1 vs. 3.1, n = 1215, p = 0.004, in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances.

  7. Asbestos-associated mesothelial cell autoantibodies promote collagen deposition in vitro

    Science.gov (United States)

    Serve, Kinta M.; Black, Brad; Szeinuk, Jaime; Pfau, Jean C.

    2016-01-01

    Fibrosis, characterized by excessive collagen protein deposition, is a progressive disease that can fatally inhibit organ function. Prolonged exposure to pathogens or environmental toxicants such as asbestos can lead to chronic inflammatory responses associated with fibrosis. Significant exposure to amphibole asbestos has been reported in and around Libby, Montana due to local mining of asbestos-contaminated vermiculite. These exposures have been implicated in a unique disease etiology characterized predominantly by pleural disorders, including fibrosis. We recently reported the discovery of mesothelial cell autoantibodies (MCAAs) in the sera of Libby residents and demonstrated a positive and significant correlation with pleural disease; however, a mechanistic link was not determined. Here we demonstrate that MCAAs induce pleural mesothelial cells to produce a collagen matrix but do not affect production of the pro-inflammatory cytokine tumor growth factor-β. While autoantibodies commonly induce a pro-fibrotic state by inducing epithelial–mesenchymal transition (EMT) of target cells, we found no evidence supporting EMT in cells exposed to MCAA positive human sera. Although implicated in other models of pulmonary fibrosis, activity of the protein SPARC (secreted protein, acidic and rich in cysteine) did not affect MCAA-induced collagen deposition. However, matrix formation was dependent on matrix metalloproteinase (MMP) activity, and we noted increased expression of MMP-8 and -9 in supernatants of mesothelial cells incubated with MCAA positive sera compared to control. These data suggest a mechanism by which MCAA binding leads to increased collagen deposition through altering MMP expression and provides an important mechanistic link between MCAAs and asbestos-related, autoimmune-induced pleural fibrosis. PMID:24304304

  8. Autoantibodies to GAD65 and IA-2 in canine diabetes mellitus.

    Science.gov (United States)

    Davison, L J; Weenink, S M; Christie, M R; Herrtage, M E; Catchpole, B

    2008-11-15

    Diabetes mellitus in dogs shares many characteristics with the human type 1 disease and virtually all diabetic dogs require insulin therapy to control hyperglycaemia. Insulin deficiency is suspected to result from immune-mediated destruction of pancreatic beta cells in some cases. Human patients suffering from Type 1A (immune-mediated) diabetes or latent autoimmune diabetes of the adult (LADA) demonstrate circulating autoantibodies against the 65kDa isoform of glutamic acid decarboxylase (GAD65) and/or insulinoma antigen-2 (IA-2). The aims of the current study were to develop radio-immunoassays to detect serum antibodies against recombinant canine GAD65 and IA-2 and to identify diabetic dogs showing serological evidence of autoreactivity to these pancreatic beta cell antigens. Canine GAD65 and the 3' end of IA-2 (coding for amino acids 771-979 of the intracellular domain) were amplified by PCR from cDNA prepared from canine insulinoma tissue and cloned into the pCRII vector. The canine sequences were later confirmed by identifying GAD2 and PTPRN genes from the dog genome assembly. Recombinant (35)S-methionine-radiolabelled canine GAD65 and IA-2 (771-979) proteins were used in radio-immunoprecipitation assays to screen sera from 30 newly diagnosed diabetic dogs and 30 control dogs. Four of 30 canine diabetic patients had significant GAD65 autoreactivity (pdogs were positive for autoantibodies to IA-2 (771-979). Two diabetic dogs showed dual autoantigen reactivity. These preliminary data indicate that serological reactivity to GAD65 and IA-2 is present in a proportion of diabetic dogs and suggests that, in some cases, canine diabetes is associated with an autoimmune response to these antigens.

  9. Autoantibodies against α-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients

    Science.gov (United States)

    Fetissov, Sergueï O.; Hallman, Jarmila; Oreland, Lars; af Klinteberg, Britt; Grenbäck, Eva; Hulting, Anna-Lena; Hökfelt, Tomas

    2002-01-01

    The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing α-melanocyte-stimulating hormone (α-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and/or BN patients studied had in their plasma Abs that bind to melanotropes and/or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to α-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with α-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with α-MSH or adrenocorticotropic hormone. Additionally, 3 AN/BN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to AN/BN staining. These data provide evidence that a significant subpopulation of AN/BN patients have autoantibodies that bind to α-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitry/LHRH system and/or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and/or could be involved in the pathophysiology or clinical presentation of AN/BN, and to what extent increased stress is an important factor for production of these autoantibodies. PMID:12486250

  10. Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation.

    Science.gov (United States)

    Lourenço, Elaine V; Liu, Aijing; Matarese, Giuseppe; La Cava, Antonio

    2016-09-20

    Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.

  11. Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

    Science.gov (United States)

    Tripathi, Prashant; Moinuddin; Dixit, Kiran; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif

    2014-07-01

    Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified with peroxynitrite, generated by quenched flow process. Modifications incurred in plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy, circular dichroism, HPLC and melting temperature studies. Binding characteristics and specificity of antibodies from diabetes patients were analyzed by direct binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid resulted in the formation of strand breaks and base modification. The major compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a specific marker for peroxynitrite induced DNA damage in inflamed tissues. The concentration of 8-nitroguanine was found to be 3.8 μM. Sera from diabetes type 1 patients from different age groups were studied for their binding to native and peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA results showed higher recognition of peroxynitrite modified plasmid, as compared to the native form, by auto-antibodies present in diabetes patients. The preferential recognition of modified plasmid by diabetes autoantibodies was further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite-modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA isolated from diabetes patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The influence of PSA autoantibodies in prostate cancer patients: a prospective clinical study-II.

    Science.gov (United States)

    Nakajima, Kosei; Heilbrun, Lance K; Smith, Daryn; Hogan, Victor; Raz, Avraham; Heath, Elisabeth

    2017-03-14

    The U.S. Preventive Services Task Force (USPSTF) has recommended against PSA-based screening for prostate cancer due to potential possibilities of false-results. Since no alternative test is available to replace it, we have initiated a trial with the purpose of establishing whether Galectin-3 (Gal-3) serum level and/or the patients' immune response to PSA and Gal-3 antigens could complement the PSA test as diagnostic tools for prostate cancer patients. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were recruited and classified into 5 different groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). The primary endpoints were the levels of serum PSA, PSA autoantibodies (AAPSA), Gal-3, and Gal-3 autoantibodies (AAGal-3). Data were analyzed by Spearman's rank correlation (rho) and least squares linear regression modeling. The expression levels of PSA, AAPSA, Gal-3, and AAGal-3 were determined in both healthy controls and prostate cancer patients. Negative correlations were observed between PSA and AAPSA levels among all 95 men combined (rho = -0.321, P = 0.0021; fitted slope -0.288, P = 0.0048), and in metastatic patients (rho = -0.472, P = 0.0413; fitted slope -1.145, P = 0.0061). We suggest an association between PSA and AAPSA, whereby the AAPSA may alter PSA levels. It provides a novel outlook for prostate cancer diagnosis, and should serve as a basis for an all-inclusive diagnostic trial centering on patients with metastasis.

  13. Dynamical encoding of looming, receding, and focussing

    Science.gov (United States)

    Longtin, Andre; Clarke, Stephen Elisha; Maler, Leonard; CenterNeural Dynamics Collaboration

    This talk will discuss a non-conventional neural coding task that may apply more broadly to many senses in higher vertebrates. We ask whether and how a non-visual sensory system can focus on an object. We present recent experimental and modeling work that shows how the early sensory circuitry of electric sense can perform such neuronal focusing that is manifested behaviorally. This sense is the main one used by weakly electric fish to navigate, locate prey and communicate in the murky waters of their natural habitat. We show that there is a distance at which the Fisher information of a neuron's response to a looming and receding object is maximized, and that this distance corresponds to a behaviorally relevant one chosen by these animals. Strikingly, this maximum occurs at a bifurcation between tonic firing and bursting. We further discuss how the invariance of this distance to signal attributes can arise, a process that first involves power-law spike frequency adaptation. The talk will also highlight the importance of expanding the classic dual neural encoding of contrast using ON and OFF cells in the context of looming and receding stimuli. The authors acknowledge support from CIHR and NSERC.

  14. 47 CFR 11.32 - EAS Encoder.

    Science.gov (United States)

    2010-10-01

    ... encoder programming shall be protected by a lock or other security measures and be configured so that... for either manual or automatic operation. (2) Inputs. The encoder shall have two inputs, one for audio... initiating the automatic generation of the simultaneous tones shall be protected to prevent accidental...

  15. Effects of diazepam on encoding processes

    NARCIS (Netherlands)

    Gorissen, M.; Eling, P.; Luijtelaar, G. van; Coenen, A.

    1995-01-01

    Benzodiazepines are known to induce amnesic effects. To specify these effects more precisely, 40 healthy volunteers were given 15 mg diazepam or placebo. Effects on a chain of encoding operations were investigated: activation of memory representations, spreading of activation, semantic encoding and

  16. The Arabic Diatessaron Project: Digitalizing, Encoding, Lemmatization

    Directory of Open Access Journals (Sweden)

    Giuliano Lancioni

    2016-04-01

    Full Text Available The Arabic Diatessaron Project (henceforth ADP is an international research project in Digital Humanities that aims to collect, digitalise and encode all known manuscripts of the Arabic Diatessaron (henceforth AD, a text that has been relatively neglected in scholarly research. ADP’s final goal is to provide a number of tools that can enable scholars to effectively query, compare and investigate all known variants of the text that will be encoded as far as possible in compliance with the Text Encoding Initiative (TEI guidelines. The paper addresses a number of issues involved in the process of digitalising manuscripts included in the two existing editions (Ciasca 1888 and Marmardji 1935, adding variants in unedited manuscripts, encoding and lemmatising the text. Issues involved in the design of the ADP include presentation of variants, choice of the standard text, applicability of TEI guidelines, automatic translation between different encodings, cross-edition concordances and principles of lemmatisation.

  17. Thyroid autoantibodies in pregnancy are associated with hypertensive disorders of pregnancy: Ma'anshan Birth Cohort Study.

    Science.gov (United States)

    Han, Yan; Mao, Lei-Jing; Ge, Xing; Huang, Kun; Yan, Shuang-Qin; Ren, Ling-Ling; Hong, Shu-Qing; Gao, Hui; Sheng, Jie; Xu, Yuan-Yuan; Pan, Wei-Jun; Zhu, Peng; Hao, Jia-Hu; Zhu, De-Fa; Tao, Fang-Biao

    2018-03-05

    Hypertensive disorders of pregnancy (HDP) have been associated with adverse health outcomes for both mothers and children. Previous studies examining associations of maternal thyroid autoantibodies with HDP indicate conflicting results. The objective of this study was to examine associations of maternal thyroid autoantibody positivity in the first and the second trimesters with the risk of HDP. In the Ma'anshan Birth Cohort study, a population-based prospective study in China, a total of 3474 pregnant women were enrolled between May 2013 and September 2014. Thyroid autoantibodies, including antithyroperoxidase autoantibody (TPOAb) and antithyroglobulin autoantibody (TgAb), as well as thyroid function tests, were measured in both the first and the second trimesters in 2893 pregnant women. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for the associations between thyroid autoantibodies and HDP. Multivariate logistic regression analyses showed that TPOAb positivity in the first trimester was associated with a 1.80 (95% CI = 1.17-2.78) increased odds of HDP after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.93, 95% CI = 1.17-3.18). In addition, TgAb positivity in the first trimester was associated with a higher risk of HDP (OR = 1.78, 95% CI = 1.16-2.73) after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.89, 95% CI = 1.15-3.11). These associations were also seen among euthyroid women. Women with positive TPOAb in the second trimester seemed to have a higher risk of gestational hypertension (OR = 1.87, 95% CI = 1.02-3.43) after adjustment for confounders. However, among euthyroid women, TPOAb positivity in the second trimester was not associated with HDP. The TgAb status in the second trimester was not associated with HDP. Our results show that TPOAb

  18. The influence of maternal islet beta-cell autoantibodies in conjunction with gestational hyperglycemia on neonatal outcomes.

    Science.gov (United States)

    Li, Zhe; Wu, Tian-mei; Ming, Wei-jie; Chen, Xin; Xiao, Xiao-min

    2015-01-01

    To determine the predictive value of the presence of maternal islet beta-cell autoantibodies with respect to neonatal outcomes. A total of 311 pregnant women with abnormal 75 g oral glucose tolerance test (OGTT) results were enrolled in this study. Maternal glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA) and insulin autoantibodies (IAA) were tested in fasting blood both on the day following the routine OGTT and before delivery. The birth weight, Apgar score, blood glucose and outcomes of each neonate were later evaluated and recorded. 1. In this study, 33.9% of the pregnant women with gestational hyperglycemia had detectable levels of one or more types of anti-islet cell antibodies in the third trimester. The proportion of women who produced GADA and/or ICA was significantly higher in the group of women with gestational hyperglycemia than in the control group (P<0.05). The groups similarly differed in the proportion of women who tested positive for any anti-islet cell antibody (P<0.05). 2. Of the patients in our study, those who produced GADA exhibited an increase in uterine and umbilical arterial pulsatility indexes (PIs) during the third trimesters compared with the control group (P˂0.05). Additionally, an increased frequency of fetal growth restriction (FGR) was observed in the infants of women who produced IAA during pregnancy compared with those without autoantibodies (P˂0.05). 3. The rate of newborn admission to the neonatal intensive care unit (NICU) was significantly associated with the presence of maternal ICA during the third trimester (OR, 6.36; 95% CI, 1.22-33.26). 4. The incidence of neonatal asphyxia was associated with the presence of maternal GADA in both the second (OR, 10.44; 95% CI, 1.46-74.92) and the third (OR, 8.33; 95% CI, 1.45-47.82) trimesters. Approximately one-third of the women with gestational hyperglycemia produced anti-islet cell antibodies. The incidence of FGR was higher in women with gestational

  19. The influence of maternal islet beta-cell autoantibodies in conjunction with gestational hyperglycemia on neonatal outcomes.

    Directory of Open Access Journals (Sweden)

    Zhe Li

    Full Text Available To determine the predictive value of the presence of maternal islet beta-cell autoantibodies with respect to neonatal outcomes.A total of 311 pregnant women with abnormal 75 g oral glucose tolerance test (OGTT results were enrolled in this study. Maternal glutamic acid decarboxylase autoantibodies (GADA, islet cell autoantibodies (ICA and insulin autoantibodies (IAA were tested in fasting blood both on the day following the routine OGTT and before delivery. The birth weight, Apgar score, blood glucose and outcomes of each neonate were later evaluated and recorded.1. In this study, 33.9% of the pregnant women with gestational hyperglycemia had detectable levels of one or more types of anti-islet cell antibodies in the third trimester. The proportion of women who produced GADA and/or ICA was significantly higher in the group of women with gestational hyperglycemia than in the control group (P<0.05. The groups similarly differed in the proportion of women who tested positive for any anti-islet cell antibody (P<0.05. 2. Of the patients in our study, those who produced GADA exhibited an increase in uterine and umbilical arterial pulsatility indexes (PIs during the third trimesters compared with the control group (P˂0.05. Additionally, an increased frequency of fetal growth restriction (FGR was observed in the infants of women who produced IAA during pregnancy compared with those without autoantibodies (P˂0.05. 3. The rate of newborn admission to the neonatal intensive care unit (NICU was significantly associated with the presence of maternal ICA during the third trimester (OR, 6.36; 95% CI, 1.22-33.26. 4. The incidence of neonatal asphyxia was associated with the presence of maternal GADA in both the second (OR, 10.44; 95% CI, 1.46-74.92 and the third (OR, 8.33; 95% CI, 1.45-47.82 trimesters.Approximately one-third of the women with gestational hyperglycemia produced anti-islet cell antibodies. The incidence of FGR was higher in women with

  20. Muscle Biopsy Findings in Combination With Myositis-Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis.

    Science.gov (United States)

    Deakin, Claire T; Yasin, Shireena A; Simou, Stefania; Arnold, Katie A; Tansley, Sarah L; Betteridge, Zoe E; McHugh, Neil J; Varsani, Hemlata; Holton, Janice L; Jacques, Thomas S; Pilkington, Clarissa A; Nistala, Kiran; Wedderburn, Lucy R

    2016-11-01

    Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM. Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations. Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0

  1. Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis

    Science.gov (United States)

    Deakin, Claire T.; Yasin, Shireena A.; Simou, Stefania; Arnold, Katie A.; Tansley, Sarah L.; Betteridge, Zoe E.; McHugh, Neil J.; Varsani, Hemlata; Holton, Janice L.; Jacques, Thomas S.; Pilkington, Clarissa A.; Nistala, Kiran; Armon, Kate; Ellis‐Gage, Joe; Roper, Holly; Briggs, Vanja; Watts, Joanna; McCann, Liza; Roberts, Ian; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; Wadeson, Susan; Riley, Phil; McGovern, Ann; Ryder, Clive; Scott, Janis; Thomas, Beverley; Southwood, Taunton; Al‐Abadi, Eslam; Wyatt, Sue; Jackson, Gillian; Amin, Tania; Wood, Mark; VanRooyen, Vanessa; Burton, Deborah; Davidson, Joyce; Gardner‐Medwin, Janet; Martin, Neil; Ferguson, Sue; Waxman, Liz; Browne, Michael; Friswell, Mark; Swift, Alison; Jandial, Sharmila; Stevenson, Vicky; Wade, Debbie; Sen, Ethan; Smith, Eve; Qiao, Lisa; Watson, Stuart; Duong, Claire; Venning, Helen; Satyapal, Rangaraj; Stretton, Elizabeth; Jordan, Mary; Mosley, Ellen; Frost, Anna; Crate, Lindsay; Warrier, Kishore; Stafford, Stefanie; Hasson, Nathan; Maillard, Sue; Halkon, Elizabeth; Brown, Virginia; Juggins, Audrey; Smith, Sally; Lunt, Sian; Enayat, Elli; Kassoumeri, Laura; Beard, Laura; Glackin, Yvonne; Almeida, Beverley; Marques, Raquel; Dowle, Stefanie; Papadopoulou, Charis; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Lee, Helen; Leach, Sam; Smith, Helen; McMahon, Anne‐Marie; Chisem, Heather; Kingshott, Ruth; Wilkinson, Nick; Inness, Emma; Kendall, Eunice; Mayers, David; Etherton, Ruth; Bailey, Kathryn; Clinch, Jacqui; Fineman, Natalie; Pluess‐Hall, Helen; Vallance, Lindsay; Akeroyd, Louise; Leahy, Alice; Collier, Amy; Cutts, Rebecca; De Graaf, Hans; Davidson, Brian; Hartfree, Sarah; Pratt, Danny

    2016-01-01

    Objective Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific autoantibodies (MSAs) have prognostic significance in juvenile DM. Methods Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow‐up 4.9 years). Long‐term treatment status (on or off medication over time) was modeled using generalized estimating equations. Results Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48‐fold higher odds (95% confidence interval [95% CI] 1.12–1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10‐fold higher odds (95% CI 1.01–1.21; P = 0.038). A protective effect was identified in patients with anti–Mi‐2 autoantibodies, in whom the odds of remaining on treatment were 7.06‐fold lower (95% CI 1.41–35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti–nuclear matrix protein 2 autoantibodies, anti–transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score

  2. Determination of auto-antibodies to native and oxidized low-density lipoproteins (LDL) in serum of patients underwent coronariography in the Medical-Surgical Research Center (MSRC)

    International Nuclear Information System (INIS)

    Conde CerdeiraI, Hector; Soto Lopez, Yosdel; Aroche Aportela, Ronald

    2010-01-01

    Low-density lipoprotein (LDL) oxidation is an important event in atherosclerosis development. The relationship between oxidized LDL (oxLDL) autoantibodies and coronary artery disease (CAD) remains controversial. IgM and IgG autoantibodies to oxLDL were measured in twenty patients undergoing clinically indicated coronary angiography, and in ten young healthy volunteers from the Center of Molecular Immunology. The levels of IgM autoantibodies to oxLDL did not differ between no CAD patients and healthy subjects, but the levels of IgM autoantibodies to oxLDL of these two groups were higher compared with the one of CAD patient group. Our results, although preliminary, supports the hypothesis that this kind of Abs might be inversely associated with the presence of atherosclerosis

  3. Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes

    DEFF Research Database (Denmark)

    Eising, Stefanie; Nilsson, Anita; Carstensen, Bendix

    2011-01-01

    A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes....

  4. A model for visual memory encoding.

    Directory of Open Access Journals (Sweden)

    Rodolphe Nenert

    Full Text Available Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA. All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN. Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

  5. A model for visual memory encoding.

    Science.gov (United States)

    Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

    2014-01-01

    Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA) with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA). All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions) and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN). Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s) of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

  6. [ENCODE apophenia or a panglossian analysis of the human genome].

    Science.gov (United States)

    Casane, Didier; Fumey, Julien; Laurenti, Patrick

    2015-01-01

    In September 2012, a batch of more than 30 articles presenting the results of the ENCODE (Encyclopaedia of DNA Elements) project was released. Many of these articles appeared in Nature and Science, the two most prestigious interdisciplinary scientific journals. Since that time, hundreds of other articles dedicated to the further analyses of the Encode data have been published. The time of hundreds of scientists and hundreds of millions of dollars were not invested in vain since this project had led to an apparent paradigm shift: contrary to the classical view, 80% of the human genome is not junk DNA, but is functional. This hypothesis has been criticized by evolutionary biologists, sometimes eagerly, and detailed refutations have been published in specialized journals with impact factors far below those that published the main contribution of the Encode project to our understanding of genome architecture. In 2014, the Encode consortium released a new batch of articles that neither suggested that 80% of the genome is functional nor commented on the disappearance of their 2012 scientific breakthrough. Unfortunately, by that time many biologists had accepted the idea that 80% of the genome is functional, or at least, that this idea is a valid alternative to the long held evolutionary genetic view that it is not. In order to understand the dynamics of the genome, it is necessary to re-examine the basics of evolutionary genetics because, not only are they well established, they also will allow us to avoid the pitfall of a panglossian interpretation of Encode. Actually, the architecture of the genome and its dynamics are the product of trade-offs between various evolutionary forces, and many structural features are not related to functional properties. In other words, evolution does not produce the best of all worlds, not even the best of all possible worlds, but only one possible world. © 2015 médecine/sciences – Inserm.

  7. Relationships among 64k Autoantibodies, Pancreatic β-cell Function, HLA-DR Antigens and HLA-DQ Genes in Patients with Insulin-Dependent Diabetes Mellitus in Korea

    Science.gov (United States)

    Lee, Hyun Chul; Cha, Bong Soo; Nam, Moon Suk; Song, Young Duk; Lim, Sung Kil; Kim, Duk Hi; Huh, Kap Bum; Koh, In Young

    1995-01-01

    Objectives Among autoantibodies detected in patients with insulin-dependent diabetes mellitus(IDDM), antibodies to 64,000Mr islet protein(64k), now recognized as glutamic acid decarboxy lase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody(ICA) or insulin autoantibody(IAA). We examined the relationships among 64k autoantibodies, pancreatic β-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea. Methods To identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed. Results 12 of 35(34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic β-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent(durationHLA-DQA1*0301, HLA-DQB1*0201, DQB1*0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12[100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11[55%] vs. without 64k autoantibody 9/22[41%]. Conclusions There results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic β-cell function in Korean patients with IDDM. PMID:7626550

  8. The level of the autoantibodies to antigenes of the thyroid gland at metabolic syndrome with deficiency of estrogens and the hypothyroidism

    Directory of Open Access Journals (Sweden)

    V. V. Kozak

    2012-08-01

    Full Text Available It has been shown that the concentration of autoantibodies to thyroperoxidase was significantly increased in rats with estrogen-deficiency. The combination of hypoestrogenia and metabolic syndrome with hypothyroidism intensified destructive processes in the thyroid gland. 17β-estradiol had the protective effect to the damaged thyroid gland in ovarioectomized animals with metabolic syndrome and hypothyroidism that was confirmed by significant reduction of concentration of autoantibodies to thyroperoxidase.

  9. Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus.

    Science.gov (United States)

    Li, Jing; Leng, Xiaomei; Li, Zhijun; Ye, Zhizhong; Li, Caifeng; Li, Xiaofeng; Zhu, Ping; Wang, Zhengang; Zheng, Yi; Li, Xiangpei; Zhang, Miaojia; Tian, Xin-Ping; Li, Mengtao; Zhao, Jiuliang; Zhang, Feng-Chun; Zhao, Yan; Zeng, Xiaofeng

    2014-01-01

    We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (Poral ulcerations (Pmanifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

  10. An autoantibody against N{sup {epsilon}}-(carboxyethyl)lysine (CEL): Possible involvement in the removal of CEL-modified proteins by macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Mera, Katsumi [Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto (Japan); Nagai, Ryoji, E-mail: nagai-883@umin.ac.jp [Department of Food and Nutrition, Laboratory of Nutritional Science and Biochemistry, Japan Women' s University, Tokyo (Japan); Takeo, Kazuhiro; Izumi, Miyoko [Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto (Japan); Maruyama, Toru [Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto (Japan); Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto (Japan); Otagiri, Masaki [Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto (Japan); Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto (Japan)

    2011-04-08

    Highlights: {yields} A higher amount of autoantibody against CEL than that of other AGEs was observed in human plasma. {yields} The purified human anti-CEL autoantibody specifically reacted with CEL. {yields} Anti-CEL antibody accelerated the uptake of {sup 125}I-CEL-HSA by macrophage in vitro. {yields} Endocytic uptake of {sup 125}I-CEL-HSA by mice liver was accelerated in the presence of anti-CEL antibody. -- Abstract: Advanced glycation end products (AGEs) are believed to play a significant role in the development of diabetic complications. In this study, we measured the levels of autoantibodies against several AGE structures in healthy human plasma and investigated the physiological role of the autoantibodies. A high titer of the autoantibody against N{sup {epsilon}}-(carboxyethyl)lysine (CEL) was detected in human plasma compared with other AGE structures such as CML and pentosidine. The purified human anti-CEL autoantibody reacted with CEL-modified human serum albumin (CEL-HSA), but not CML-HSA. A rabbit polyclonal anti-CEL antibody, used as a model autoantibody against CEL, accelerated the uptake of CEL-HSA by macrophages, but did not enhance the uptake of native HSA. Furthermore, when {sup 125}I-labeled CEL-HSA was injected into the tail vein of mice, accumulation of {sup 125}I-CEL-HSA in the liver was accelerated by co-injection of the rabbit anti-CEL antibody. These results demonstrate that the autoantibody against CEL in plasma may play a role in the macrophage uptake of CEL-modified proteins.

  11. Enhanced tactile encoding and memory recognition in congenital blindness.

    Science.gov (United States)

    D'Angiulli, Amedeo; Waraich, Paul

    2002-06-01

    Several behavioural studies have shown that early-blind persons possess superior tactile skills. Since neurophysiological data show that early-blind persons recruit visual as well as somatosensory cortex to carry out tactile processing (cross-modal plasticity), blind persons' sharper tactile skills may be related to cortical re-organisation resulting from loss of vision early in their life. To examine the nature of blind individuals' tactile superiority and its implications for cross-modal plasticity, we compared the tactile performance of congenitally totally blind, low-vision and sighted children on raised-line picture identification test and re-test, assessing effects of task familiarity, exploratory strategy and memory recognition. What distinguished the blind from the other children was higher memory recognition and higher tactile encoding associated with efficient exploration. These results suggest that enhanced perceptual encoding and recognition memory may be two cognitive correlates of cross-modal plasticity in congenital blindness.

  12. Encoding of coordination complexes with XML.

    Science.gov (United States)

    Vinoth, P; Sankar, P

    2017-09-01

    An in-silico system to encode structure, bonding and properties of coordination complexes is developed. The encoding is achieved through a semantic XML markup frame. Composition of the coordination complexes is captured in terms of central atom and ligands. Structural information of central atom is detailed in terms of electron status of valence electron orbitals. The ligands are encoded with specific reference to the electron environment of ligand centre atoms. Behaviour of ligands to form low or high spin complexes is accomplished by assigning a Ligand Centre Value to every ligand based on the electronic environment of ligand centre atom. Chemical ontologies are used for categorization purpose and to control different hybridization schemes. Complexes formed by the central atoms of transition metal, non-transition elements belonging to s-block, p-block and f-block are encoded with a generic encoding platform. Complexes of homoleptic, heteroleptic and bridged types are also covered by this encoding system. Utility of the encoded system to predict redox electron transfer reaction in the coordination complexes is demonstrated with a simple application. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Efficient reverse time migration with amplitude encoding

    Science.gov (United States)

    Hu, Jiangtao; Wang, Huazhong; Zhao, Lei; Shao, Yu; Wang, Meixia; Osen, Are

    2015-08-01

    Reverse time migration (RTM) is an accurate seismic imaging method for imaging the complex subsurface structure. Traditional common shot RTM suffers from low efficiency due to the large number of single shot gathers, especially for marine seismic data. Phase encoding is commonly used to reduce the computational cost of RTM. Phase encoding in the frequency domain is usually related to time shift in the time domain. Therefore, phase-encoding-based RTM needs time padding to avoid information loss which degrades the efficiency of the time-domain wavefield extrapolator. In this paper, an efficient time-domain RTM scheme based on the amplitude encoding is proposed. This scheme uses the orthogonal cosine basis as the encoding function, which has similar physical meaning to plane wave encoding (i.e. plane-wave components with different surface shooting angles). The proposed scheme can generate a qualified imaging result as well as common shot RTM but with less computational cost. Since this scheme does not need time padding, it is more efficient than the phase encoding schemes and can be conveniently implemented in the time domain. Numerical examples on the Sigsbee2a synthetic dataset demonstrate the feasibility of the proposed method.

  14. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

    DEFF Research Database (Denmark)

    Blixt, Ola; Bueti, Deanna; Burford, Brian

    2011-01-01

    ABSTRACT: INTRODUCTION: Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed the serum assay widely...... used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before...... the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients. METHODS: We used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer...

  15. ADAMTS13 and anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura - current perspectives and new treatment strategies.

    Science.gov (United States)

    Tersteeg, Claudia; Verhenne, Sebastien; Roose, Elien; Schelpe, An-Sofie; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-01-01

    A deficiency in ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type-1 repeats, member 13) is associated with thrombotic thrombocytopenic purpura (TTP). Congenital TTP is caused by a defect in the ADAMTS13 gene resulting in decreased or absent enzyme activity; acquired TTP results from autoantibodies that either inhibit the activity or increase the clearance of ADAMTS13. Despite major progress in recent years in our understanding of the disease, many aspects around the pathophysiology of TTP are still unclear. Newer studies expanded the TTP field from ADAMTS13 and inhibitory antibodies to immune complexes, cloned autoantibodies, and a possible involvement of other proteases. Additionally, several new treatment strategies supplementing plasma-exchange and infusion are under investigation for a better and more specific treatment of TTP patients. In this review, we discuss the recent insights in TTP pathophysiology and describe upcoming therapeutic opportunities.

  16. Selfies. Symmetry_Encoding_Life_Fakes_Insight_Encoding_Science

    Directory of Open Access Journals (Sweden)

    Paolo Amodio

    2014-12-01

    Full Text Available By observing through the microscope a biological structure at the different scale levels, it is possible to live an astonishing experience which leads the explorer to travel across hierarchically structured geometrical worlds where spaces and paths are established by forms of unexpected strictness and symmetrical constructions conceal nested architectures which create self-similar universes evoking Koch's fractals or three-dimensional versions of Mandelbrot sets. The finding – surprising and consolatory at the same time – that living matter can somehow exhibit symmetries and levels of order one generally (and only associates to inorganic crystals, de facto undermines the foundations of some dichotomous categories on which both Science and Philosophy are based, consequently making fluid the boundaries between organic and inorganic, artificial and natural and – at the end – between life and death. The Life – at the macro- and micro-scopic eye – is available. It is geometrical disposition, conformal symmetry, solution and result. But Life, where that eye (and its extents is slotted, is meta-order, at most World as energy and kinematic laps, anyway para-logical priority, logical noise, paradox of the tangible and of the material. So, Science and Philosophy become comment and/or protest of the human mind in front of a “There Is”, and in this blame game between meta-bio-logical prius and historical preemption, any result of the human mind is also a result of the Life, of physical and chemical auto-organization which allows the Life itself. Not only methodological explosion of dichotomies as Natural/Artificial, Organic/Inorganic – the practice or the break of the dichotomy is however an existential demand of the Logos – rather secret horizon required by human livings, mass-produced mirrors of self-references and semantic codes. Symmetries and violations of symmetries in piles of Selfies to post on social networks of Science and

  17. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks.

    Directory of Open Access Journals (Sweden)

    Paul Tonelli

    Full Text Available A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1 the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2 synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT. Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1 in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2 whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities.

  18. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks.

    Science.gov (United States)

    Tonelli, Paul; Mouret, Jean-Baptiste

    2013-01-01

    A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2) synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT). Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1) in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2) whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities.

  19. Disease specificity of autoantibodies to cytosolic 5'-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases.

    Science.gov (United States)

    Herbert, Megan K; Stammen-Vogelzangs, Judith; Verbeek, Marcel M; Rietveld, Anke; Lundberg, Ingrid E; Chinoy, Hector; Lamb, Janine A; Cooper, Robert G; Roberts, Mark; Badrising, Umesh A; De Bleecker, Jan L; Machado, Pedro M; Hanna, Michael G; Plestilova, Lenka; Vencovsky, Jiri; van Engelen, Baziel G; Pruijn, Ger J M

    2016-04-01

    The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies

    Science.gov (United States)

    Meulenbroek, Elisabeth M.; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S.; Wouters, Diana

    2015-01-01

    In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient’s erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients’ sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients’ sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients’ erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy. PMID:26354757

  1. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies

    OpenAIRE

    Mahler, Michael; Meroni, Pier-Luigi; Bossuyt, Xavier; Fritzler, Marvin J

    2014-01-01

    The detection of autoantibodies that target intracellular antigens, commonly termed anti-nuclear antibodies (ANA), is a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). Different methods are available for detection of ANA and all bearing their own advantages and limitations. Most laboratories use the indirect immunofluorescence (IIF) assay based on HEp-2 cell substrates. Due to the subjectivity of this diagnostic platform, automated digital reading syste...

  2. Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.

    Science.gov (United States)

    Achenbach, Peter; Hawa, Mohammed I; Krause, Stephanie; Lampasona, Vito; Jerram, Samuel T; Williams, Alistair J K; Bonifacio, Ezio; Ziegler, Anette G; Leslie, R David

    2018-04-04

    Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy. Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study with sufficient sera, we selected those designated type 1 (n = 511) or type 2 diabetes (n = 603) and retested the samples in radiobinding assays for human full-length GAD65 autoantibodies (f-GADA) and N-terminally truncated (amino acids 96-585) GAD65 autoantibodies (t-GADA). Individuals' clinical phenotypes were analysed according to antibody binding patterns. Overall, 478 individuals were f-GADA-positive, 431 were t-GADA-positive and 628 were negative in both assays. Risk of insulin treatment was augmented in t-GADA-positive individuals (OR 4.69 [95% CI 3.57, 6.17]) compared with f-GADA-positive individuals (OR 3.86 [95% CI 2.95, 5.06]), irrespective of diabetes duration. Of 55 individuals who were f-GADA-positive but t-GADA-negative, i.e. with antibody binding restricted to the N-terminus of GAD65, the phenotype was similar to type 2 diabetes with low risk of progression to insulin treatment. Compared with these individuals with N-terminal GAD65-restricted GADA, t-GADA-positive individuals were younger at diagnosis (p = 0.005), leaner (p N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.

  3. Serum Th1 and Th17 related cytokines and autoantibodies in patients with Posner-Schlossman syndrome.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Posner-Schlossman syndrome (PSS shares some clinical features with uveitis and open angle glaucoma. Cytokines and autoantibodies have been associated with uveitis and open angle glaucoma. However, the role of serum cytokines and autoantibodies in the pathogenesis of PSS remains unknown. This study aimed to evaluate the associations of type 1 T helper (Th1 and Th17 related cytokines and autoantibodies with PSS. Peripheral blood serum samples were collected from 81 patients with PSS and 97 gender- and age-matched healthy blood donors. Th1 and Th17 related cytokines, including interleukin-1β (IL-1β, IL-12, tumor necrosis factor-α (TNF-α, interferon- γ (IFN-γ, IL-6 and IL-17, and glucose-6-phosphate isomerase (GPI were determined by double antibody sandwich ELISA. Anti-nuclear antibody (ANA, anti-keratin antibody (AKA and anti-neutrophil cytoplasmic antibody (ANCA were detected by indirect immunofluorescence assay. Anti-cardiolipin antibody (ACA-IgG, ACA-IgM, ACA-IgA, anti-double stranded DNA (anti-dsDNA and anti-cyclic citrullinated peptide antibody (anti-CCP were detected by indirect ELISA. Serum levels of IL-1β, IL-12 and IL-6 in PSS patients were significantly lower than those in controls (P 0.12. Positive rate of serum anti-dsDNA in PSS patients was significantly higher than that in the control group (P = 0.002, Pc = 0.018, while positive rates of serum ANA, AKA, ANCA, ACA-IgG, ACA-IgM, ACA-IgA, GPI and anti-CCP in the PSS group were not significantly different from those in the control group (Pc > 0.09. These results suggest that anti-dsDNA may contribute to the pathogenesis of PSS, while Th1 and Th17 related cytokines and other autoantibodies may not be major contributors to PSS.

  4. Profile of autoantibodies against phosphorylcholine and cross-reactivity to oxidation-specific neoantigens in selective IgA deficiency with or without autoimmune diseases.

    Science.gov (United States)

    Fusaro, Ana Elisa; Fahl, Kristine; Cardoso, Elaine Cristina; de Brito, Cyro Alves; Jacob, Cristina M A; Carneiro-Sampaio, Magda; Duarte, Alberto J S; Sato, Maria Notomi

    2010-11-01

    Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

  5. Encoding and Decoding Models in Cognitive Electrophysiology

    Directory of Open Access Journals (Sweden)

    Christopher R. Holdgraf

    2017-09-01

    Full Text Available Cognitive neuroscience has seen rapid growth in the size and complexity of data recorded from the human brain as well as in the computational tools available to analyze this data. This data explosion has resulted in an increased use of multivariate, model-based methods for asking neuroscience questions, allowing scientists to investigate multiple hypotheses with a single dataset, to use complex, time-varying stimuli, and to study the human brain under more naturalistic conditions. These tools come in the form of “Encoding” models, in which stimulus features are used to model brain activity, and “Decoding” models, in which neural features are used to generated a stimulus output. Here we review the current state of encoding and decoding models in cognitive electrophysiology and provide a practical guide toward conducting experiments and analyses in this emerging field. Our examples focus on using linear models in the study of human language and audition. We show how to calculate auditory receptive fields from natural sounds as well as how to decode neural recordings to predict speech. The paper aims to be a useful tutorial to these approaches, and a practical introduction to using machine learning and applied statistics to build models of neural activity. The data analytic approaches we discuss may also be applied to other sensory modalities, motor systems, and cognitive systems, and we cover some examples in these areas. In addition, a collection of Jupyter notebooks is publicly available as a complement to the material covered in this paper, providing code examples and tutorials for predictive modeling in python. The aim is to provide a practical understanding of predictive modeling of human brain data and to propose best-practices in conducting these analyses.

  6. Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA.

    Science.gov (United States)

    Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A

    2017-12-01

    Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Removal of dental amalgam decreases anti-TPO and anti-Tg autoantibodies in patients with autoimmune thyroiditis.

    Science.gov (United States)

    Sterzl, Ivan; Prochazkova, Jarmila; Hrda, Pavlina; Matucha, Petr; Bartova, Jirina; Stejskal, Vera

    2006-12-01

    The impact of dental amalgam removal on the levels of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies was studied in patients with autoimmune thyroiditis (AT) with and without mercury allergy. Thirty-nine patients with AT were tested by an optimized lymphocyte proliferation test MELISA for allergy (hypersensitivity) to inorganic mercury. Patients were divided into two groups: Group I (n = 12) with no hypersensitivity to mercury and Group II (n = 27) with hypersensitivity to mercury. Amalgam fillings were removed from the oral cavities of 15 patients with hypersensitivity to mercury (Group IIA) and left in place in the remaining 12 patients (Group IIB). The laboratory markers of AT, anti-TPO and anti-Tg autoantibodies, were determined in all groups at the beginning of the study and six months later. Compared to levels at the beginning of the study, only patients with mercury hypersensitivity who underwent amalgam replacement (Group IIA) showed a significant decrease in the levels of both anti-Tg (p=0.001) and anti-TPO (p=0.0007) autoantibodies. The levels of autoantibodies in patients with or without mercury hypersensitivity (Group I and Group IIB) who did not replace amalgam did not change. Removal of mercury-containing dental amalgam in patients with mercury hypersensitivity may contribute to successful treatment of autoimmune thyroiditis.

  8. A patient with Graves’ disease showing only psychiatric symptoms and negativity for both TSH receptor autoantibody and thyroid stimulating antibody

    Directory of Open Access Journals (Sweden)

    Hamasaki Hidetaka

    2012-12-01

    Full Text Available Abstract Background Both thyroid stimulating hormone (TSH and thyroid stimulating antibody (TSAb negative Graves’s disease (GD is extremely rare. Here we present such a patient. Case presentation The patient was a 76-year-old woman who was diagnosed as having schizophrenia forty years ago. She did not show characteristic symptoms for hyperthyroidism, such as swelling of thyroid, exophthalmos, tachycardia and tremor, however, she showed only psychomotor agitation. Serum free triiodothyronine and free thyroxine levels were elevated and TSH level was suppressed, suggesting the existence of hyperthyroidism. However, both the first generation TSH receptor autoantibody (TRAb1 and the thyroid stimulating autoantibody (TSAb were negative. Slightly increased blood flow and swelling was detected by thyroid echography. Thyroid scintigraphy demonstrated diffuse and remarkably elevated uptake of 123I uptake. Finally, we diagnosed her as having GD. She was treated by using methimazole, and hyperthyroidism and her psychiatric symptoms were promptly ameliorated. Discussion We experienced a patient with GD who did not show characteristic symptoms except for psychiatric symptoms, and also showed negativity for both TRAb1 and TSAb. Thyroid autoantibody-negative GD is extremely rare. Thyroid scintigraphy was useful to diagnose such a patient.

  9. Carbonic Anhydrases III and IV Autoantibodies in Rheumatoid Arthritis, Systemic Lupus Erythematosus, Diabetes, Hypertensive Renal Disease, and Heart Failure

    Directory of Open Access Journals (Sweden)

    Chengeng Liu

    2012-01-01

    Full Text Available In the present study, the CA III and IV autoantibodies, CA activity, antioxidant enzymes and cytokines in rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, diabetes, hypertensive renal disease, and heart failure were investigated. The anti-CA III antibody titers in patients with RA, SLE, and type 1 diabetes (T1D were significantly higher than that in control groups (P<0.05. The anti-CA IV antibody titers in patients with RA, SLE, type 1 diabetic nephropathy (T1DN, and heart failure were significantly higher than that in control groups (P<0.05 while anti-CA IV antibody could suppress the total CA activity. The SOD and GPx levels in patients with RA, SLE, and T1DN were significantly lower than that in control groups (P<0.05. IL-6, IL-17, IFN-γ, and TNF-α levels were significantly higher in SLE group compared with the control group (P<0.05. Weak but significant correlations were found between anti-CA III antibodies and ESR in RA (r=0.403, P=0.013 and SLE patients (r=0.397, P=0.007. These results suggested that the generation of CA III and IV autoantibodies, antioxidant enzymes, and cytokines might influence each other and CA autoantibodies might affect the normal physiology function of CA.

  10. An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice.

    Science.gov (United States)

    Nelson, R K; Gould, K A

    2016-02-01

    Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell-specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB × NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4(+) and CD8(+) T cells, the proportion of activated CD4(+) T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cell apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. © The Author(s) 2015.

  11. An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice

    Science.gov (United States)

    Nelson, Richard K.; Gould, Karen A.

    2015-01-01

    Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB×NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4+ and CD8+ T cells, the proportion of activated CD4+ T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cells apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. PMID:26385218

  12. Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange.

    Science.gov (United States)

    Iversen, Rasmus; Mysling, Simon; Hnida, Kathrin; Jørgensen, Thomas J D; Sollid, Ludvig M

    2014-12-02

    The multifunctional enzyme transglutaminase 2 (TG2) is the target of autoantibodies in the gluten-sensitive enteropathy celiac disease. In addition, the enzyme is responsible for deamidation of gluten peptides, which are subsequently targeted by T cells. To understand the regulation of TG2 activity and the enzyme's role as an autoantigen in celiac disease, we have addressed structural properties of TG2 in solution by using hydrogen/deuterium exchange monitored by mass spectrometry. We demonstrate that Ca(2+) binding, which is necessary for TG2 activity, induces structural changes in the catalytic core domain of the enzyme. Cysteine oxidation was found to abolish these changes, suggesting a mechanism whereby disulfide bond formation inactivates the enzyme. Further, by using TG2-specific human monoclonal antibodies generated from intestinal plasma cells of celiac disease patients, we observed that binding of TG2 by autoantibodies can induce structural changes that could be relevant for the pathogenesis. Detailed mapping of two of the main epitopes targeted by celiac disease autoantibodies revealed that they are located adjacent to each other in the N-terminal part of the TG2 molecule.

  13. Complete elimination of cardiodepressant IgG3 autoantibodies by immunoadsorption in patients with severe heart failure

    International Nuclear Information System (INIS)

    Baba, Akiyasu; Akaishi, Makoto; Shimada, Megumi; Wakabayashi, Yasuhisa; Takahashi, Michiko; Monkawa, Toshiaki; Nagatomo, Yuji; Yoshikawa, Tsutomu

    2010-01-01

    Cardiodepressant IgG3 autoantibodies (CD-Abs) can be targeted by apheresis. Using blinded measurements of CD-Abs before and after immunoadsorption (IA), the cardiac function of patients who did or did not achieve complete CD-Abs elimination was compared. Autoantibodies were completely removed from 18 patients with heart failure (New York Heart Association class 3 or 4, left ventricular ejection fraction (LVEF) <30%) using a selective IgG3 adsorption column. All patients had anti-β1-adrenergic and/or M2-muscarinic autoantibodies before IA, and all LVEF were measured on radionuclide ventriculography. CD-Abs were measured before and after IA, and patient status was blinded until all measurements were collected. Treatment was defined as complete when CD-Abs status changed from positive to negative after IA. Other instances were defined as incomplete. Six-min walk test results and brain natriuretic peptide levels improved significantly after IA (P<0.01). The increase in LVEF 3 months after IA was significantly greater after complete treatment in comparison to the incomplete treatment group (19±8-29±9% vs 18±9-17±8%, P<0.01). Cardiac insufficiency events were also more frequent in the incomplete treatment group. Complete elimination of CD-Abs with apheresis may be related to improved cardiac function in the treatment of heart failure. (author)

  14. Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Tanay, A.; Strober, S.; Logue, G.L.; Schiffman, G.

    1984-01-01

    The effect of total lymphoid irradiation (TLI) on T cell-dependent and -independent humoral immune responses was studied in patients with intractable rheumatoid arthritis (RA). The serum levels of several autoantibodies and of antibodies to diphtheria (DT) and tetanus (TT) toxoids and to pneumococcal polysaccharide (PPS; 12 antigenic types) were studied before and after TLI. In addition, the patients were given a booster injection of DT and TT and a single injection of pneumococcal vaccine after radiotherapy. Antibody levels to DT and TT decreased about twofold after TLI and did not rise significantly after a booster injection. However, there was no reduction in antibody levels to PPS after TLI, and a significant rise in titers was observed after a single vaccination. The serum levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and granulocyte associated IgG rose slightly after TLI. Thus, the autoantibodies and antibodies to polysaccharides appear to be relatively independent of helper T cell function, which is markedly reduced after TLI. On the other hand, antibodies to protein antigens such as DT and TT appear to be more closely dependent upon T helper function in man, as has been reported in rodents. The findings suggest that T cell-independent autoantibody responses alone do not maintain the joint disease activity in RA, because improvement in joint disease after TLI has been reported

  15. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Saygili, Erol, E-mail: erol.saygili@med.uni-duesseldorf.de [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Noor-Ebad, Fawad; Schröder, Jörg W.; Mischke, Karl [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Saygili, Esra [Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Rackauskas, Gediminas [Department of Cardiovascular Medicine, Vilnius University Hospital Santariskiu Klinikos, Vilnius University (Lithuania); Marx, Nikolaus [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Kelm, Malte; Rana, Obaida R. [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany)

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing factors

  16. A rapid method of detecting autoantibody against FcεRIα for chronic spontaneous urticaria.

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    Mey-Fann Lee

    Full Text Available BACKGROUND: Chronic spontaneous urticaria (CU is a common skin disorder, with an estimated prevalence of 0.5-1.8% in most populations. Around 30-50% of CU patients have an autoimmune etiology, with autoantibodies (autoAbs against IgE, FcεRIα, and FcεRII/CD23. Although the in vivo autologous serum skin test (ASST and in vitro histamine release/activation assay are the most frequently used screening methods, these two have many limitations and do not directly measure susceptible autoAbs. This study aimed to establish an in vitro rapid screening test using recombinant autoantigen FcεRIα(rFcεRIα to improve the diagnosis of autoimmune urticaria. METHODS: Forty patients with CU and 20 healthy individuals were enrolled. After PCR-based cloning and the production of extracellular fragments of the FcεRIα protein using the E. coli expression system, serum autoAb to rFcεRIα was evaluated using in-house ELISA and rapid immunodot test. RESULTS: In ELISA-based detection, 14 out of 20 CU-ASST(+ patients exhibited anti- FcεRIα responses, whereas five of the 20 CU-ASST(- and two of the 20 non-CU patients showed autoantibody background in the assay. For the immunodot test, 55% (11/20 of the CU-ASST(+ sera exhibited anti-FcεRIα reactivity. There was no false positive among the CU-ASST(- and non-CU groups. Using clinical urticaria plus ASST(+ as the gold standard, in-house ELISA had 70% sensitivity, 82.5% specificity, and positive likelihood ratio of 4, while immunodot had 55% sensitivity, 100% specificity, and positive likelihood ratio >55. CONCLUSIONS: This study has developed a rapid immunodot method with high specificity for detecting autoAb to FcεRIαin patients with CU. Preliminary data indicates that this immunodot technique has the potential to be a routine diagnostic assay for autoimmune CU.

  17. Immunofluorescence pattern of antinuclear antibody and its association with autoantibody profile in systemic lupus erythematosus

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    Sadia Sharmin

    2016-08-01

    Full Text Available Background: Antinuclear antibody (ANA is useful in the diagnosis of systemic lupus erythematosus (SLE. Association of specific autoantibodies with the immunofluorescence pattern of ANA in SLE as noted in Western literature has been taken as reference in all over the world. However, in Bangladesh such research work or data correlating the autoantibodies and their ANA patterns is inadequate. Objective: To identify an association between immunofluorescence patterns of antinuclear antibody on HEp-2 cell and more specific antinuclear reactivities (e.g. anti-dsDNA and anti-extractable nuclear antigen in the serum samples of SLE patients.Methods: Serum samples of 37 SLE patients who were diagnosed by ARA (American Rheumatism Association classification criteria and laboratory tests, attending at lupus clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU during the study period of six months were subjected for ANA testing by Indirect Imrnunofluorescence (IIF on HEp-2 cell, anti-dsDNA by ELISA and anti- extractable nuclear antigen (anti-ENA by Dot Immunoblot. Dot blot strips were tested for anti-Sm, anti-RNP, anti-SSA/Ro, and anti-SSB/La. Results: Out of 37 SLE patients 32 (86.5% cases were ANA positive by IIF on HEp-2 cell. ANA positive sera exhibited three fluorescence patterns such as speckled (43.7%, peripheral (34.3% and homogenous pattern (21.8%. Peripheral pattern (100% was strongly associated with anti-dsDNA (p<0.05 and homogenous pattern (85.7% was also predominantly associated with anti-dsDNA (p<0.05. Speckled pattern (85.6% was significantly associated with anti-ENA (p<0.05. Anti-dsDNA was positive in 75% of SLE cases and majority (45.8% of which showed peripheral pattern whereas anti-ENA was positive in 48.6% cases and majority (70.5% of which showed speckled pattern. The most commonly identified antinuclear autoreactivity was directed towards anti-RNP (22.2% then anti-Sm (16.6%, anti-SSA (16.6% and anti-SSB (11.1 %. Multiple anti

  18. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Zebedeo, Christian Nash; Davis, Chad [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States); Peña, Cecelia [Northwest Nazarene University, Nampa, ID (United States); Ng, Kok Wei [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States); Pfau, Jean C., E-mail: pfaujean@isu.edu [Department of Biological Sciences, Idaho State University, Pocatello, ID (United States)

    2014-03-15

    Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were

  19. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    International Nuclear Information System (INIS)

    Zebedeo, Christian Nash; Davis, Chad; Peña, Cecelia; Ng, Kok Wei; Pfau, Jean C.

    2014-01-01

    Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T H 17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were distinct

  20. [Reference Intervals of Thyroid Hormones in Normal Pregnant Women and Effects of Thyroid Autoantibodies on Thyroid Hormone Levels in Pregnant Women in Chengdu Area].

    Science.gov (United States)

    Chen, Yu-Min; Zeng, Jing; Yan, Yue-Rong; Luo, Dan; Huang, Lu; Huang, Hui

    2017-05-01

    To establish the reference intervals of thyroid hormones in normal pregnant women in Chengdu area of China, and to investigate the effects of thyroid autoantibodies on thyroid function in pregnant women. We included 696 pregnant women who had gestation data from June 2013 to March 2014 in Chengdu Women & Children's Central Hospital. Every subject under went questionnaire survey, physical examination, thyroid ultrasound and measurement of thyroid hormone and thyroid autoantibodies. The normal reference intervals were established according to the percentiles (P 2.5 -P 97.5 ) of the healthy pregnant women in the same trimester. Another 50 non-pregnant women were selected as the control group. Of the 696 pregnant women, 579 subjects had negative thyroid autoantibodies and 117 subjects had positive thyroid autoantibodies. The positive rate of thyroid autoantibodies was 16.81%. Of the 579 subjects with negative thyroid autoantibodies, 257 were in the first trimester, 202 in the second trimester and 120 in the third trimester. In the first trimester of normal pregnancy, the reference intervals of serum thyrotropin (TSH) , free triiodothyronine (FT3) and free thyroxine (FT4) were 0.02-4.03 mIU/L, 3.85-6.27 pmol/L and 11.93-21.04 pmol/L respectively. In the second trimester, the reference intervals of serum TSH, FT3 and FT4 were 0.02-4.05 mIU/L, 3.51-5.82 pmol/L and 11.23-19.22 pmol/L respectively. In the thirdtrimester, the reference intervals for serum TSH, FT3 and FT4 were 0.24-5.41 mIU/L, 3.18-4.97 pmol/L and 11.10-17.00 pmol/L, respectively. When compared with non-pregnant women, the median TSH value was increasingly consisted with the progress of pregnancy period, while the median FT4 and FT3 values were decreasing accordingly. The similar tendencies of TSH, FT3, and FT4 were found in pregnant women with positive thyroid autoantibodies, but the trends were more remarkable when compared with those with negative thyroid autoantibodies. In pregnant women with positive

  1. Using XML to encode TMA DES metadata.

    Science.gov (United States)

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  2. Using XML to encode TMA DES metadata

    Directory of Open Access Journals (Sweden)

    Oliver Lyttleton

    2011-01-01

    Full Text Available Background: The Tissue Microarray Data Exchange Specification (TMA DES is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  3. Natural gas; Gas Natural

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Carlos A.; Moraes, Claudia C.D. [Eletricidade de Sao Paulo S.A. (ELETROPAULO), Sao Paulo, SP (Brazil); Fonseca, Carlos H.F. [Centrais Eletricas de Santa Catarina S.A., Florianopolis, SC (Brazil); Silva, Clecio Fabricio da; Alves, Ricardo P. [Companhia Paranaense de Energia (COPEL), Curitiba, PR (Brazil); Sposito, Edivaldo Soares; Hulle, Lutero [Espirito Santo Centrais Eletricas S.A. (ESCELSA), Vitoria, ES (Brazil); S. Martins, Icaro da [Centrais Eletricas do Norte do Brasil S.A. (ELETRONORTE), Belem, PA (Brazil); Vilhena, Joao Luiz S. de [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil); Fagundes, Zaluar Aquino [Companhia Estadual de Energia Eletrica do Estado do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    1996-12-31

    An increase in the consumption of natural gas in Brazil is an expected fact in what concerns energetic planning. This work presents the existing situation in what concerns natural gas utilization in the main world economies, as well as an analysis of the participation of this fuel among the energy final consumption per sources. The Brazilian consumption of natural gas is also analysed as well as the international agreement between Brazil and Bolivia for natural gas commercialization. Some legal, institutional and political aspects related to natural gas commercialization are also discussed. Finally, several benefits to be brought by the utilization of natural gas are presented 10 refs., 3 tabs.

  4. Aphid-encoded variability in susceptibility to a parasitoid.

    Science.gov (United States)

    Martinez, Adam J; Ritter, Shannon G; Doremus, Matthew R; Russell, Jacob A; Oliver, Kerry M

    2014-06-10

    Many animals exhibit variation in resistance to specific natural enemies. Such variation may be encoded in their genomes or derived from infection with protective symbionts. The pea aphid, Acyrthosiphon pisum, for example, exhibits tremendous variation in susceptibility to a common natural enemy, the parasitic wasp Aphidius ervi. Pea aphids are often infected with the heritable bacterial symbiont, Hamiltonella defensa, which confers partial to complete resistance against this parasitoid depending on bacterial strain and associated bacteriophages. That previous studies found that pea aphids without H. defensa (or other symbionts) were generally susceptible to parasitism, together with observations of a limited encapsulation response, suggested that pea aphids largely rely on infection with H. defensa for protection against parasitoids. However, the limited number of uninfected clones previously examined, and our recent report of two symbiont-free resistant clones, led us to explicitly examine aphid-encoded variability in resistance to parasitoids. After rigorous screening for known and unknown symbionts, and microsatellite genotyping to confirm clonal identity, we conducted parasitism assays using fifteen clonal pea aphid lines. We recovered significant variability in aphid-encoded resistance, with variation levels comparable to that contributed by H. defensa. Because resistance can be costly, we also measured aphid longevity and cumulative fecundity of the most and least resistant aphid lines under permissive conditions, but found no trade-offs between higher resistance and these fitness parameters. These results indicate that pea aphid resistance to A. ervi is more complex than previously appreciated, and that aphids employ multiple tactics to aid in their defense. While we did not detect a tradeoff, these may become apparent under stressful conditions or when resistant and susceptible aphids are in direct competition. Understanding sources and amounts of

  5. Fatal Mycobacterium colombiense/cytomegalovirus coinfection associated with acquired immunodeficiency due to autoantibodies against interferon gamma: a case report

    Directory of Open Access Journals (Sweden)

    Poulin Sébastien

    2013-01-01

    Full Text Available Abstract Background Reports of acquired immunodeficiency due to autoantibodies against interferon gamma in the adult population are increasing. The interleukin-12-dependent interferon-gamma axis is a major regulatory pathway of cell-mediated immunity and is critical for protection against a few intracellular organisms, including non-tuberculous mycobacteria and Salmonella spp. We report the first case of a fatal disseminated Mycobacterium colombiense/cytomegalovirus coinfection in an adult woman associated with the acquisition of autoantibodies against interferon-gamma. Case presentation A 49-year-old woman, born to nonconsanguineous parents in Laos, but who had lived in Canada for the past 30 years, presented with a 1-month history of weight loss, fatigue, cough, and intermittent low-grade fever. A thoracic computed tomography scan revealed an 8 × 7 cm irregular mass impacting the right superior lobar bronchus along with multiple mediastinal and hilar adenopathies. On the fourth day of admission, the patient developed fever with purulent expectorations. Treatment for a post-obstructive bacterial pneumonia was initiated while other investigations were being pursued. Almost every culture performed during the patient’s hospitalization was positive for M. colombiense. Given the late presentation of symptoms - at the age of 49 years - and the absence of significant family or personal medical history, we suspected an acquired immunodeficiency due to the presence of anti-interferon-gamma autoantibodies. This was confirmed by their detection at high levels in the plasma and a STAT1 phosphorylation assay on human monocytes. The final diagnosis was immunodeficiency secondary to the production of autoantibodies against interferon-gamma, which resulted in a post-obstructive pneumonia and disseminated infection of M. colombiense. The clinical course was complicated by the presence of a multiresistant Pseudomonas aeruginosa post-endobronchial ultrasound

  6. Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients.

    Science.gov (United States)

    Sarkadi, Adrien Katalin; Taskó, Szilvia; Csorba, Gabriella; Tóth, Beáta; Erdős, Melinda; Maródi, László

    2014-02-01

    The relative roles of various autoantibodies against IL-17-type cytokines in susceptibility to chronic mucocutaneous candidiasis (CMC) in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) remain poorly defined. The purpose of this longitudinal study was to analyze the relationship between the occurrence of mucocutaneous candidiasis and levels of anti-IL-17A, anti-IL-17F and anti-IL-22 autoantibodies. We studied six APECED patients from four families with various disease manifestations. Clinical data were collected during regular follow-up. Anti-endocrine organ antibody levels and clinical chemistry and immunology parameters were determined in routine laboratory assays on freshly isolated serum. Levels of autoantibodies against IL-17A, IL-17F, IL-22, IFN-α, IFN-ω and TNF-α, and cytokine release by Candida-exposed blood cells were determined by ELISA. Mutations were analyzed by sequencing genomic DNA. Four patients carried the germline c.769C > T homozygous nonsense mutation, which results in R257X truncation of the AIRE protein, and two patients from the same family were compound heterozygous for the c.769C > T/c.1344delC mutation. We found persistently high levels of antibodies against IL-17A in the serum samples of one patient presenting CMC since infancy and low or undetectable anti-IL-17A antibody levels in the sera of five patients with no candidiasis or without severe candidiasis. By contrast, levels of autoantibodies against IL-17F and IL-22 were higher in all patients than in healthy controls. Release of IL-17-type cytokines by Candida-exposed blood mononuclear cells was low or negligible in all patients tested. We suggest that anti-IL-17A antibodies may play an important role in the predisposition to candidiasis of APECED patients. However, the lack of severe CMC in APECED patients with high levels of IL-17F and anti-IL-22 autoantibodies clearly calls into question the role of these antibodies as the principal

  7. Blocking and binding folate receptor alpha autoantibodies identify novel autism spectrum disorder subgroups

    Directory of Open Access Journals (Sweden)

    Richard Eugene Frye

    2016-03-01

    Full Text Available Folate receptor α (FRα autoantibodies (FRAAs are prevalent in autism spectrum disorder (ASD. They disrupt the transportation of folate across the blood-brain barrier by binding to the FRα. Children with ASD with FRAAs have been reported to respond well to treatment with a form of folate known as folinic acid, suggesting that they may be an important ASD subgroup to identify and treat. There has been no investigation of whether they manifest unique behavioral and physiological characteristics. Thus, in this study we measured both blocking and binding FRAAs, physiological measurements including indices of redox and methylation metabolism and inflammation as well as serum folate and B12 concentrations and measurements of development and behavior in 94 children with ASD. Children positive for the binding FRAA were found to have higher serum B12 levels as compared to those negative for binding FRAAs while children positive for the blocking FRAA were found to have relatively better redox metabolism and inflammation markers as compared to those negative for blocking FRAAs. In addition, ASD children positive for the blocking FRAA demonstrated better communication on the Vineland Adaptive Behavior Scale, stereotyped behavior on the Aberrant Behavioral Checklist and Mannerisms on the Social Responsiveness Scale. This study suggests that FRAAs are associated with specific physiological and behavioral characteristics in children with ASD and provides support for the notion that these biomarkers may be useful for subgrouping children with ASD, especially with respect to targeted treatments.

  8. Pemphigus vulgaris in a Welsh pony stallion: case report and demonstration of antidesmoglein autoantibodies.

    Science.gov (United States)

    Winfield, Laramie D; White, Stephen D; Affolter, Verena K; Renier, Anna C; Dawson, Dominic; Olivry, Thierry; Outerbridge, Catherine A; Wang, Yu Hsuan; Iyori, Keita; Nishifuji, Koji

    2013-04-01

    To describe the clinical, histological and immunological findings of an equine case of pemphigus vulgaris, including the demonstration of antidesmoglein (anti-Dsg) autoantibodies. The diagnosis of pemphigus vulgaris was confirmed in a 9-year-old Welsh pony stallion with both direct and indirect immunofluorescence and immunoprecipitation studies, the latter identifying circulating anti-Dsg3 IgG. Treatment with immunosuppressive medications was initiated. Lesions were seen in the perineal area, sheath, mane, tail, eyelids, coronary bands and mucosa of the mouth and oesophagus. Initial corticosteroid treatment improved the clinical signs, but the onset of laminitis necessitated a reduction in dosage, which was associated with a recurrence of lesions and development of oral ulcers. A corneal ulcer developed after 60 days of treatment. Despite treatment with azathioprine, gold salts and dapsone, the disease progressed and the pony was euthanized. Postmortem examination showed additional lesions of the cardia of the stomach. Pemphigus vulgaris is rarely diagnosed in equids. We describe a case that was substantiated by the demonstration of anti-Dsg3 IgG. Response to treatment was poor, with the best response to high doses of prednisolone. Equine pemphigus vulgaris is likely to carry a poor prognosis and if there is no response to treatment, humane euthanasia is warranted. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

  9. Systemic lupus erythematosus presenting as hypoglycaemia with insulin receptor antibodies and insulin autoantibodies.

    Science.gov (United States)

    Qing, Y; Zhou, J-G; Yuan, G

    2009-04-01

    A 37-year-old man presented with sweating, confusion, palpitations, hunger and tremor of 3 months duration. The symptoms disappeared after ingestion of food. After 3 months, he suffered from irregular fever, arthritis, rash, photosensitivity, and was admitted to the hospital. His antinuclear antibody, anti-double stranded DNA antibody, anti-smith antibody and lupus erythematosus cell phenomenon were all positive. Urine analysis showed albuminuria; his 24-h urine protein was 4.7 g. During hospitalisation, the patient presented with loss of consciousness three times because of hypoglycaemia. His serum insulin level during the hypoglycaemic episode was high at 490-1080 mmol/L (normal range: 6.00-27.00 mmol/L). He had never received an insulin rejection. Both insulin autoantibody and insulin receptor antibody were positive. Investigations confirmed systemic lupus erythematosus (SLE) with autoimmune hypoglycaemia. High-dose of corticosteroids, chloroquine and cyclophosphamide therapy had resulted in remission of hypoglycaemia associated with resolution of circulating antibodies to insulin and insulin receptor, and improvement in clinical and laboratory features of SLE.

  10. Effect of Autoantibodies to Erythropoietin Receptor in Systemic Lupus Erythematosus with Biopsy-proven Lupus Nephritis.

    Science.gov (United States)

    Hara, Akinori; Furuichi, Kengo; Yamahana, Junya; Yasuda, Haruka; Iwata, Yasunori; Sakai, Norihiko; Shimizu, Miho; Kaneko, Shuichi; Wada, Takashi

    2016-07-01

    We examined the clinical significance of autoantibodies to the erythropoietin receptor (EPOR) in patients with systemic lupus erythematosus (SLE) who had biopsy-proven lupus nephritis (LN). Forty-six Japanese patients with SLE with LN who had undergone renal biopsy during 1993-2014 were enrolled in this study and followed for a mean of 83 months. Sera from those patients were screened for anti-EPOR antibodies using ELISA. Anti-EPOR antibodies were detected in 18 (39%) of the 46 patients with SLE with anemia. Anti-EPOR antibodies were associated with low hemoglobin concentrations and reticulocytopenia. In addition, anti-EPOR antibodies were positively correlated with SLE disease activity, even though serum levels of the complement factors 3 and 4 did not differ between the 2 groups. In patients with International Society of Nephrology/Renal Pathology Society 2003 class IV LN, anti-EPOR antibodies were associated with active lesions including cellular crescents in glomeruli. Decrease in renal function was more frequently observed in patients without complete or partial renal response than in patients with it, and serum levels of the antibodies as well as renal response to treatment were significant risk factors for progression of renal dysfunction. The present study suggests that anti-EPOR antibodies might be involved in overall disease activity and active renal lesions, as well as in the impaired erythropoiesis in patients with SLE with LN. Further, the levels of anti-EPOR antibodies may be an additional predictor for renal injury.

  11. BAFF promotes autoantibody production via TACI-dependent activation of transitional B cells

    Science.gov (United States)

    Jacobs, Holly M.; Thouvenel, Christopher D.; Leach, Sarah; Arkatkar, Tanvi; Metzler, Genita; Scharping, Nicole E.; Kolhatkar, Nikita S.; Rawlings, David J.; Jackson, Shaun W.

    2016-01-01

    Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear antibodies. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remains unclear. We now report that, whereas surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACIhi transitional cells from BAFF-Tg mice are characterized by an activated, cycling phenotype; and the TACIhi cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase (AID) and T-bet and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACIhi transitional B cells from BAFF-Tg mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism whereby BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells. PMID:27022196

  12. Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation of Transitional B Cells.

    Science.gov (United States)

    Jacobs, Holly M; Thouvenel, Christopher D; Leach, Sarah; Arkatkar, Tanvi; Metzler, Genita; Scharping, Nicole E; Kolhatkar, Nikita S; Rawlings, David J; Jackson, Shaun W

    2016-05-01

    Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear Abs. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remain unclear. We report that, although surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACI(+) transitional cells from BAFF-transgenic mice are characterized by an activated, cycling phenotype, and the TACI(+) cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase and T-bet, and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells from BAFF-transgenic mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism through which BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  13. Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn's disease.

    Science.gov (United States)

    Gathungu, Grace; Kim, Mi-Ok; Ferguson, John P; Sharma, Yashoda; Zhang, Wei; Ng, Sok Meng E; Bonkowski, Erin; Ning, Kaida; Simms, Lisa A; Croft, Anthony R; Stempak, Joanne M; Walker, Nicole; Huang, Ning; Xiao, Yang; Silverberg, Mark S; Trapnell, Bruce; Cho, Judy H; Radford-Smith, Graham L; Denson, Lee A

    2013-07-01

    Neutralizing autoantibodies (Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF Ab) have been associated with stricturing ileal Crohn's disease (CD) in a largely pediatric patient cohort (total 394, adult CD 57). The aim of this study was to examine this association in 2 independent predominantly adult inflammatory bowel disease patient cohorts. Serum samples from 742 subjects from the NIDDK IBD Genetics Consortium and 736 subjects from Australia were analyzed for GM-CSF Ab and genetic markers. We conducted multiple regression analysis with backward elimination to assess the contribution of GM-CSF Ab levels and established CD risk alleles and smoking on ileal disease location in the 477 combined CD subjects from both cohorts. We also determined associations of GM-CSF Ab levels with complications requiring surgical intervention in combined CD subjects in both cohorts. Serum samples from patients with CD expressed significantly higher concentrations of GM-CSF Ab when compared with ulcerative colitis or controls in each cohort. Nonsmokers with ileal CD expressed significantly higher GM-CSF Ab concentrations in the Australian cohort (P = 0.002). Elevated GM-CSF Ab, ileal disease location, and disease duration more than 3 years were independently associated with stricturing/penetrating behavior and intestinal resection for CD. The expression of high GM-CSF Ab is a risk marker for aggressive CD behavior and complications including surgery. Modifying factors include environmental exposure to smoking and genetic risk markers.

  14. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen.

    Science.gov (United States)

    Ponomarenko, Natalia A; Durova, Oxana M; Vorobiev, Ivan I; Belogurov, Alexey A; Kurkova, Inna N; Petrenko, Alexander G; Telegin, Georgy B; Suchkov, Sergey V; Kiselev, Sergey L; Lagarkova, Maria A; Govorun, Vadim M; Serebryakova, Marina V; Avalle, Bérangère; Tornatore, Pete; Karavanov, Alexander; Morse, Herbert C; Thomas, Daniel; Friboulet, Alain; Gabibov, Alexander G

    2006-01-10

    Autoantibody-mediated tissue destruction is among the main features of organ-specific autoimmunity. This report describes "an antibody enzyme" (abzyme) contribution to the site-specific degradation of a neural antigen. We detected proteolytic activity toward myelin basic protein (MBP) in the fraction of antibodies purified from the sera of humans with multiple sclerosis (MS) and mice with induced experimental allergic encephalomyelitis. Chromatography and zymography data demonstrated that the proteolytic activity of this preparation was exclusively associated with the antibodies. No activity was found in the IgG fraction of healthy donors. The human and murine abzymes efficiently cleaved MBP but not other protein substrates tested. The sites of MBP cleavage determined by mass spectrometry were localized within immunodominant regions of MBP. The abzymes could also cleave recombinant substrates containing encephalytogenic MBP(85-101) peptide. An established MS therapeutic Copaxone appeared to be a specific abzyme inhibitor. Thus, the discovered epitope-specific antibody-mediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with MS.

  15. Fatal warm autoimmune hemolytic anemia in a child due to IgM-type autoantibodies.

    Science.gov (United States)

    Takahashi, Hiroyuki; Tanaka, Fumiko; Sakuma, Hiroyuki; Sato, Mutsumi; Inaba, Shoichi; Kai, Sumio

    2016-08-01

    Herein is described a case of immunoglobulin M (IgM) warm autoimmune hemolytic anemia (AIHA) in a child who consequently died within 3 days of clinical onset. A previously healthy 11-year-old boy presented with fever, anemia, jaundice, and deteriorating consciousness. On direct agglutination test against group O red blood cells, agglutination was seen even at 37°C in saline, which was abolished on dithiothreitol treatment of the serum, indicating that the responsible autoantibody was IgM and had a warm-reactive capacity. A diagnosis of IgM warm AIHA was therefore made. Hemagglutination in the visceral capillaries was considered as the direct cause of organ dysfunction. The patient died due to respiratory failure. IgM warm AIHA is a very severe condition that is difficult to reverse in an advanced state. Both prompt, definite diagnosis and intervention are therefore vital to prevent severe multi-organ dysfunction in cases of IgM warm AIHA. © 2016 Japan Pediatric Society.

  16. Automated Indirect Immunofluorescence Evaluation of Antinuclear Autoantibodies on HEp-2 Cells

    Directory of Open Access Journals (Sweden)

    Jörn Voigt

    2012-01-01

    Full Text Available Indirect immunofluorescence (IIF on human epithelial (HEp-2 cells is considered as the gold standard screening method for the detection of antinuclear autoantibodies (ANA. However, in terms of automation and standardization, it has not been able to keep pace with most other analytical techniques used in diagnostic laboratories. Although there are already some automation solutions for IIF incubation in the market, the automation of result evaluation is still in its infancy. Therefore, the EUROPattern Suite has been developed as a comprehensive automated processing and interpretation system for standardized and efficient ANA detection by HEp-2 cell-based IIF. In this study, the automated pattern recognition was compared to conventional visual interpretation in a total of 351 sera. In the discrimination of positive from negative samples, concordant results between visual and automated evaluation were obtained for 349 sera (99.4%, kappa = 0.984. The system missed out none of the 272 antibody-positive samples and identified 77 out of 79 visually negative samples (analytical sensitivity/specificity: 100%/97.5%. Moreover, 94.0% of all main antibody patterns were recognized correctly by the software. Owing to its performance characteristics, EUROPattern enables fast, objective, and economic IIF ANA analysis and has the potential to reduce intra- and interlaboratory variability.

  17. Automated indirect immunofluorescence evaluation of antinuclear autoantibodies on HEp-2 cells.

    Science.gov (United States)

    Voigt, Jörn; Krause, Christopher; Rohwäder, Edda; Saschenbrecker, Sandra; Hahn, Melanie; Danckwardt, Maick; Feirer, Christian; Ens, Konstantin; Fechner, Kai; Barth, Erhardt; Martinetz, Thomas; Stöcker, Winfried

    2012-01-01

    Indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells is considered as the gold standard screening method for the detection of antinuclear autoantibodies (ANA). However, in terms of automation and standardization, it has not been able to keep pace with most other analytical techniques used in diagnostic laboratories. Although there are already some automation solutions for IIF incubation in the market, the automation of result evaluation is still in its infancy. Therefore, the EUROPattern Suite has been developed as a comprehensive automated processing and interpretation system for standardized and efficient ANA detection by HEp-2 cell-based IIF. In this study, the automated pattern recognition was compared to conventional visual interpretation in a total of 351 sera. In the discrimination of positive from negative samples, concordant results between visual and automated evaluation were obtained for 349 sera (99.4%, kappa = 0.984). The system missed out none of the 272 antibody-positive samples and identified 77 out of 79 visually negative samples (analytical sensitivity/specificity: 100%/97.5%). Moreover, 94.0% of all main antibody patterns were recognized correctly by the software. Owing to its performance characteristics, EUROPattern enables fast, objective, and economic IIF ANA analysis and has the potential to reduce intra- and interlaboratory variability.

  18. Comparison of disease activity measures for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis

    Science.gov (United States)

    Merkel, PA; Cuthbertson, DD; Hellmich, B; Hoffman, GS; Jayne, DRW; Kallenberg, CGM; Krischer, JP; Luqmani, R; Mahr, AD; Matteson, EL; Specks, U; Stone, JH

    2011-01-01

    Aim Currently, several different instruments are used to measure disease activity and extent in clinical trials of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, leading to division among investigative groups and difficulty comparing study results. An exercise comparing six different vasculitis instruments was performed. Methods A total of 10 experienced vasculitis investigators from 5 countries scored 20 cases in the literature of Wegener granulomatosis or microscopic polyangiitis using 6 disease assessment tools: the Birmingham Vasculitis Activity Score (BVAS), The BVAS for Wegener granulomatosis (BVAS/WG), BVAS 2003, a Physician Global Assessment (PGA), the Disease Extent Index (DEI) and the Five Factor Score (FFS). Five cases were rescored by all raters. Results Reliability of the measures was extremely high (intraclass correlations for the six measures all=0.98). Within each instrument, there were no significant differences or outliers among the scores from the 10 investigators. Test/retest reliability was high for each measure: range=0.77 to 0.95. The scores of the five acute activity measures correlated extremely well with one another. Conclusions Currently available tools for measuring disease extent and activity in ANCA-associated vasculitis are highly correlated and reliable. These results provide investigators with confidence to compare different clinical trial data and helps form common ground as international research groups develop new, improved and universally accepted vasculitis disease assessment instruments. PMID:18664546

  19. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

    DEFF Research Database (Denmark)

    Fosgerau, K; Galle, P; Hansen, T

    2010-01-01

    Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct...... role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6...... were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when...

  20. Tumor-associated auto-antibodies as early detection markers for ovarian cancer?

    DEFF Research Database (Denmark)

    Kaaks, Rudolf; Fortner, Renée Turzanski; Hüsing, Anika

    2018-01-01

    .08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all......Immuno-proteomic screening has identified several tumor-associated auto-antibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs...... under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0...

  1. Refractory chronic epilepsy associated with neuronal auto-antibodies: could perisylvian semiology be a clue?

    Science.gov (United States)

    Gillinder, Lisa; Tjoa, Linda; Mantzioris, Basil; Blum, Stefan; Dionisio, Sasha

    2017-12-01

    We report a case series of 10 patients with chronic medically refractory antibody-positive autoimmune epilepsy and assess their common clinical features. Immune-mediated seizures are most commonly reported in the context of encephalitis or encephalopathy, with few reports focusing on lone, chronic epilepsy in the outpatient setting. Our aim was to define the potential diagnostic clues that might be present in these cases, leading to consideration of an autoimmune cause of the epilepsy. We performed a retrospective review of all patients presenting to the outpatient department of our unit who underwent autoimmune screening. All patients with chronic epilepsy and a positive result for an antibody known to be associated with epilepsy were included. Sixty-three patients underwent testing. Thirteen returned a positive result, however, only 10 of these were patients which chronic epilepsy who did not present with an acute illness. Common features in these cases included: perisylvian semiology, EEG abnormalities in the mid temporal region, normal or non-specific MRI findings, depression, and head injury. In cases of medically refractory, lesion-negative epilepsy, with predominantly perisylvian semiology, clinicians should have a high level of suspicion for the diagnosis of autoimmune aetiologies and a low threshold to perform autoantibody screening. This is especially true if there are atypical electrographic findings, a previous history of head injury, or co-morbid depression.

  2. Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case-control study.

    Science.gov (United States)

    Toulis, Konstantinos A; Goulis, Dimitrios G; Tsolakidou, Konstantina; Hilidis, Ilias; Fragkos, Marios; Polyzos, Stergios A; Gerofotis, Antonios; Kita, Marina; Bili, Helen; Vavilis, Dimitrios; Daniilidis, Michail; Tarlatzis, Basil C; Papadimas, Ioannis

    2013-08-01

    We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

  3. Should we systematically test patients with clinically isolated syndrome for auto-antibodies?

    Science.gov (United States)

    Negrotto, Laura; Tur, Carmen; Tintoré, Mar; Arrambide, Georgina; Sastre-Garriga, Jaume; Río, Jordi; Comabella, Manuel; Nos, Carlos; Galán, Ingrid; Vidal-Jordana, Angela; Simon, Eva; Castilló, Joaquín; Palavra, Filipe; Mitjana, Raquel; Auger, Cristina; Rovira, Àlex; Montalban, Xavier

    2015-12-01

    Several autoimmune diseases (ADs) can mimic multiple sclerosis (MS). For this reason, testing for auto-antibodies (auto-Abs) is often included in the diagnostic work-up of patients with a clinically isolated syndrome (CIS). The purpose was to study how useful it was to systematically determine antinuclear-antibodies, anti-SSA and anti-SSB in a non-selected cohort of CIS patients, regarding the identification of other ADs that could represent an alternative diagnosis. From a prospective CIS cohort, we selected 772 patients in which auto-Ab levels were tested within the first year from CIS. Baseline characteristics of auto-Ab positive and negative patients were compared. A retrospective revision of clinical records was then performed in the auto-Ab positive patients to identify those who developed ADs during follow-up. One or more auto-Ab were present in 29.4% of patients. Only 1.8% of patients developed other ADs during a mean follow-up of 6.6 years. In none of these cases the concurrent AD was considered the cause of the CIS. In all cases the diagnosis of the AD resulted from the development of signs and/or symptoms suggestive of each disease. Antinuclear-antibodies, anti-SSA and anti-SSB should not be routinely determined in CIS patients but only in those presenting symptoms suggestive of other ADs. © The Author(s), 2015.

  4. Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders

    Directory of Open Access Journals (Sweden)

    Grazyna Adamus

    2017-04-01

    Full Text Available Autoantibodies (AAbs against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. AAbs against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation of AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but the retina may be without pathological consequence until a failure of the blood–retinal barrier function, which would then allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.

  5. Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

    Science.gov (United States)

    Yang, J; Li, Q; Yang, X; Li, M

    2016-04-01

    Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

  6. Do associated auto-antibodies influence the outcome of myasthenia gravis after thymectomy?

    Science.gov (United States)

    Keijzers, Marlies; Damoiseaux, Jan; Vigneron, Alain; Bodart, Nicolas; Kessels, Alfons; Dingemans, Anne-Marie C; Hochstenbag, Monique; Maessen, Jos; De Baets, Marc

    2015-01-01

    Myasthenia gravis (MG) is a neuromuscular autoimmune disease, where antibodies against the acetylcholine receptor destroy this receptor. The role of thymectomy in the treatment of MG remains controversial. Because of the frequent association with other autoimmune diseases, we hypothesized that patients with multiple autoantibodies (autoAbs) might have a lower chance of reaching complete stable remission after thymectomy. We analyzed sera of 85 MG patients who underwent a thymectomy between April 2004 and December 2012. We used four different immunodot kits (D-Tek, Mons, Belgium): ANA25 Quantrix, Synthetase 10 Diver, Myositis 7 Diver and Liver 10 profile Diver, all automatized on the BlueDiver Instrument (D-Tek). The Myasthenia Gravis Foundation of America (MGFA) postintervention status was used to determ