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Sample records for autoantibodies

  1. Autoantibody pain.

    Science.gov (United States)

    Goebel, Andreas

    2016-06-01

    As autoantibodies bind to target tissues, Fc-region dependent inflammation can induce pain via mediators exciting nociceptors. But recently another possibility has emerged, where autoantibody binding to nociceptors can directly cause pain, without inflammation. This is thought to occur as a result of Fab-region mediated modification of nerve transduction, transmission, or neuropeptide release. In three conditions, complex regional pain syndrome, anti-voltage gated potassium channel complex autoimmunity, and chronic fatigue syndrome, all associated with no or only little inflammation, initial laboratory-, and clinical trial-results have suggested a potential role for autoantibody-mediated mechanisms. More research assessing the pathogenic roles of autoantibodies in these and other chronic pain conditions is required. The concept of autoantibody-mediated pain offers hope for the development of novel therapies for currently intractable pains. PMID:26883460

  2. Islet Autoantibodies.

    Science.gov (United States)

    Lampasona, Vito; Liberati, Daniela

    2016-06-01

    Islet autoantibodies are the main markers of pancreatic autoimmunity in type 1 diabetes (T1D). Islet autoantibodies recognize insulin (IAA), glutamic acid decarboxylase (GADA), protein phosphatase-like IA-2 (IA-2A), and ZnT8 (ZnT8A), all antigens that are found on secretory granules within pancreatic beta cells. Islet antibodies, measured by sensitive and specific liquid phase assays, are the key parameters of the autoimmune response monitored for diagnostics or prognostics in patients with T1D or for disease prediction in at-risk individuals before T1D onset. Islet autoantibodies have been the main tool used to explore the natural history of T1D; this review summarizes the current knowledge about the autoantigens and the phenotype of islets autoantibodies acquired in large prospective studies from birth in children at risk of developing T1D. PMID:27112957

  3. 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.

  4. Autoantibodies in inflammatory arthritis.

    Science.gov (United States)

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides. PMID:26970491

  5. 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...

  6. 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.

  7. Autoantibody Profile in Systemic Sclerosis

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    Marvin J Fritzler

    2010-02-01

    Full Text Available Systemic sclerosis is a generalized disorder of connective tissue clinically characterized by thickening and fibrosis of the skin and by distinctive forms of involvement of internal organs. One of the hallmarks of systemic sclerosis is the presence of serum autoantibodies against a variety of nuclear and cytoplasmic antigens. The primary purpose of this study was to identify the autoantibodies profile in the scleroderma sera and the secondary goal was to determine the correlation and discrepancy of autoantibody profile. Autoantibody profile was determined in 118 samples stored in the Advanced Diagnostic Laboratory at the University of Calgary. 78 sera were provided from Canadian and 40 sera were provided from Ukraine. We used the following techniques to identify autoantibodies profile in scleroderma patients: 1. Antinuclear antibody (ANA by indirect immunofluorescence on human epithelial cell substrate 2. Detection and identification of specific autoantibodies by Innolia strip assay 3. Detection and identification of specific autoantibodies against extractable nuclear antigens. 111 out of 118 patients showed positive ANA results by indirect immunofluorescence and 7 patients had negative ANA results. Anti-ENA analyses by Inolia were positive in 84 patients, while by western blotting 81 patients showed positive results. In this study, we compared the results of anti-ENA antibody by Innolia with SLR technique. A significant correlation was found between anti-SCl-70 antibodies (P=0.000 and anti- RNP antibodies (P=0.001 and JO-1 antibodies (P=0.014. Thus, we may propose that SLR and Innolia techniques could be used for the detection of autoantibody in systemic sclerosis.

  8. Autoantibodies in Patients with Fasciolosis

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    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.

  9. 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.

  10. Myositis specific autoantibodies : specificity and clinical applications

    NARCIS (Netherlands)

    Hengstman, G.J.D.

    2005-01-01

    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as compar

  11. Are There Enhanced MBP Autoantibodies in Autism?

    Science.gov (United States)

    Libbey, Jane E.; Coon, Hilary H.; Kirkman, Nikki J.; Sweeten, Thayne L.; Miller, Judith N.; Stevenson, Edward K.; Lainhart, Janet E.; McMahon, William M.; Fujinami, Robert S.

    2008-01-01

    Autoantibodies to central nervous system antigens, such as myelin basic protein (MBP), may play a role in autism. We measured autoantibody titers to MBP in children with autism, both classic onset and regressive onset forms, controls (healthy age- and gender-matched) and individuals with Tourette syndrome via enzyme-linked immunosorbent assays. We…

  12. The Role of Pathogenic Autoantibodies in Autoimmunity

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    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.

  13. Mechanisms of Action of TSHR Autoantibodies.

    Science.gov (United States)

    Furmaniak, J; Sanders, J; Núñez Miguel, R; Rees Smith, B

    2015-09-01

    The availability of human monoclonal antibodies (MAbs) to the TSHR has enabled major advances in our understanding of how TSHR autoantibodies interact with the receptor. These advances include determination of the crystal structures of the TSHR LRD in complex with a stimulating autoantibody (M22) and with a blocking type autoantibody (K1-70). The high affinity of MAbs for the TSHR makes them particularly suitable for use as ligands in assays for patient serum TSHR autoantibodies. Also, M22 and K1-70 are effective at low concentrations in vivo as TSHR agonists and antagonists respectively. K1-70 has important potential in the treatment of the hyperthyroidism of Graves' disease and Graves' ophthalmopathy. Small molecule TSHR antagonists described to date do not appear to have the potency and/or specificity shown by K1-70. New models of the TSHR ECD in complex with various ligands have been built. These models suggest that initial binding of TSH to the TSHR causes a conformational change in the hormone. This opens a positively charged pocket in receptor-bound TSH which attracts the negatively charged sulphated tyrosine 385 on the hinge region of the receptor. The ensuing movement of the receptor's hinge region may then cause activation. Similar activation mechanisms seem to take place in the case of FSH and the FSHR and LH and the LHR. However, stimulating TSHR autoantibodies do not appear to activate the TSHR in the same way as TSH. PMID:26361260

  14. Autoantibodies, autoimmune disease, and the birth of immune diagnostics

    OpenAIRE

    Tan, Eng M.

    2012-01-01

    The appearance of autoantibody to DNA followed sequentially by the disappearance of anti-DNA and appearance of DNA antigen in a patient with systemic lupus erythematosus demonstrated that autoantibodies participate in immune complex–mediated pathogenesis. Continuing studies showed that autoantibodies are also useful biomarkers in clinical diagnosis and important reagents for elucidating the structure and function of intracellular proteins in cell biology. Recently, autoantibodi...

  15. Autoantigens and autoantibodies in multiple sclerosis.

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    Abbas Mirshafiey

    2013-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by recurrent episodes of demyelination and axonal lesion mediated by CD4+ T cells with a proinflammatory T helper (Th1 and Th17 phenotypes, macrophages, and soluble inflammatory mediators. The overactive pro-inflammatory Th1 cells and clonal expansion of B cells initiate an inflammatory cascade with several cellular and molecular immune components participating in MS pathogenic mechanisms. In this scenario, autoantibodies and autoantigens have a significant role in immunopathogenesis, diagnosis and therapeutic targets of MS. In this review, we try to introduce the autoantigens and autoantibodies and explain their roles in pathogenesis of MS.

  16. Subchorionic hematomas and the presence of autoantibodies.

    Science.gov (United States)

    Baxi, L V; Pearlstone, M M

    1991-11-01

    Five cases of subchorionic hematoma detected by ultrasonography in patients with threatened abortion are presented. Three of these subjects had antinuclear antibodies, and the remaining two subjects had anticardiolipin antibodies. We recommend that patients with subchorionic hematomas be tested for autoantibodies regardless of their obstetric history. PMID:1957874

  17. Autoantibodies in SLE: Specificities, Isotypes and Receptors

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    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.

  18. Anti-C1q autoantibodies

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2008-01-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this co

  19. Wegener's granulomatosis and autoantibodies to neutrophil antigens

    OpenAIRE

    McCluskey, D R; Maxwell, A. P.; Watt, L

    1988-01-01

    We report five cases of Wegener's granulomatosis all of whom had clinical and histological evidence of disease activity at presentation and in whom autoantibodies to neutrophil antigens were detected. This test may prove useful for the diagnosis of this serious condition and help to monitor disease activity during treatment.

  20. Autoantibody profiling in systemic lupus erythematosus

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    Hsieh SC

    2013-08-01

    Full Text Available Song-Chou Hsieh,1 Chia-Li Yu1,2 1Department of Internal Medicine, 2Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Abstract: Systemic lupus erythematosus (SLE is an archetype of systemic autoimmune disease characterized by the production of a broad spectrum of autoantibodies. More than 100 autoantibodies have been found in the sera of patients with SLE, including antibodies against nuclear, cytoplasmic, surface-membrane, and extracellular antigens. There has been considerable debate as to whether these antinuclear autoantibodies (ANAs are merely biomarkers for disease or are responsible for organ/tissue damage in SLE. In recent years, sufficient evidence has supported the hypothesis that many ANAs, such as anti-double-stranded DNA (anti-dsDNA, antiribosomal P, anti-Sm, antiribonucleoprotein (anti-RNP, and even anti-Sjögren's syndrome (SS-B/La antibodies not only act against specific nuclear antigens but also cross-react with different surface-expressed cognate molecules. The binding of autoantibodies to the cell surface leads to their penetration into the cell's interior to elicit cellular damage. There are at least four conceivable routes for ANAs to penetrate the cytoplasm: (1 nonspecific Fcγ receptor-mediated uptake, (2 cell-surface caveolae-mediated endocytosis, (3 electrostatic interactions between positively charged amino acids of the complementarity-determining regions of the antibody molecule and the negatively charged surface membrane, and (4 the binding of the autoantibody with its cross-reactive cell surface-expressed cognate molecule, and its subsequent endocytosis into the cytoplasm. In this review, we discuss in detail the immunopathogenic mechanisms of the commonly encountered ANAs, such as anti-dsDNA, antiribosomal P, and anti-SSB/La, that are associated with lupus pathogenesis. Additionally, the detrimental thromboembolism-inducing anticardiolipin antibodies in patients with SLE

  1. Frequency and levels of autoantibodies in healthy adult Omanis

    International Nuclear Information System (INIS)

    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

  2. Anti-C1q autoantibodies.

    Science.gov (United States)

    Kallenberg, Cees G M

    2008-09-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this condition. They occur, however, more frequently in (proliferative) lupus nephritis, particularly during active disease. Furthermore, levels of anti-C1q rise, in many cases, prior to a relapse of lupus nephritis, suggesting a pathogenic role for the autoantibodies. Indeed, experimental studies strongly support a pathogenic role for anti-C1q in immune complex-mediated renal disease. In addition, anti-C1q may interfere with the clearance of apoptotic cells, so influencing induction and expression of autoimmunity. PMID:18606253

  3. Strategies for building reference standards for autoantibodies.

    Science.gov (United States)

    Sheldon, Joanna; Dellavance, Alessandra

    2015-01-01

    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. PMID:25972866

  4. 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.

  5. Detection of autoantibodies using chemiluminescence technologies

    OpenAIRE

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

    2015-01-01

    Abstract Context: 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 t...

  6. Prevalence of pemphigus and pemphigoid autoantibodies in the general population

    OpenAIRE

    Prüßmann, Wiebke; Prüßmann, Jasper; Koga, Hiroshi; Recke, Andreas; Iwata, Hiroaki; Juhl, David; Görg, Siegfried; Henschler, Reinhard; HASHIMOTO, TAKASHI; Schmidt, Enno; Zillikens, Detlef; Ibrahim, Saleh M.; Ludwig, Ralf J

    2015-01-01

    Background Mucocutaneous blistering is characteristic of autoimmune bullous dermatoses (AIBD). Blisters are caused by autoantibodies directed against structural components of the skin. Hence, detection of specific autoantibodies has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD autoantibodies in healthy individuals yielded contradictory results. Methods To clarify this, samples from 7063 blood donors were tested for presence of anti-BP180-NC16A, anti-BP230 and anti-Dsg1/...

  7. Measurement of TSH receptor autoantibodies in thyroid diagnosis

    International Nuclear Information System (INIS)

    In 462 patients the TSH receptor autoantibodies were measured by use of a commercially available kit (Henning-Berlin). The results were divided into four groups according to the results of function tests, scintigraphy and sonography. Most of the positive cases of TSH receptor autoantibody measurements were related to patients with increased thyroid function and homogenous activity distribution in the thyroidgland. Using 6% as lowest positive value for finding TSH receptor autoantibodies the specivicity of the test was 75% and the sensitivity 94%. Measuring TSH receptor autoantibodies seems to be useful for follow-up of patients during therapy with immunogenic hyperthyroidism. (orig.)

  8. AT2R autoantibodies block angiotensin II and AT1R autoantibody-induced vasoconstriction.

    Science.gov (United States)

    Liles, Campbell; Li, Hongliang; Veitla, Vineet; Liles, Jonathan T; Murphy, Taylor A; Cunningham, Madeleine W; Yu, Xichun; Kem, David C

    2015-10-01

    Activating autoantibodies to the angiotensin type 1 receptor (AT1R) are associated with hypertensive disorders. The angiotensin type 2 receptor (AT2R) is known to counter-regulate the actions of AT1R. We investigated whether AT2R autoantibodies produced in immunized rabbits will activate AT2R and suppress the vasopressor responses to angiotensin II and AT1R-activating autoantibodies. Five rabbits immunized with a peptide corresponding to the second extracellular loop of AT2R developed high AT2R antibody titers. Rabbit anti-AT2R sera failed to directly dilate isolated rat cremaster arterioles; however, when co-perfused with angiotensin II or AT1R-activating autoantibodies, the anti-AT2R sera significantly inhibited their contractile effects. Rabbit anti-AT2R sera recognized a predominant sequence near the N-terminus of the AT2R second extracellular loop. A decoy peptide based on this sequence effectively reversed the opposing effect of the anti-AT2R sera on angiotensin II-induced contraction of rat cremaster arterioles. A similar blockade of the anti-AT2R sera effect was observed with the AT2R antagonist PD 123319 and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Rabbit anti-AT2R sera reacted specifically with AT2R. No cross-reactivity with AT1R was observed. Blood pressure did not change in immunized animals. However, the pressor responses to incremental angiotensin II infusions were blunted in immunized animals. Thirteen subjects with primary aldosteronism demonstrated increased AT2R autoantibody levels compared with normal controls. In conclusion, AT2R autoantibodies produced in immunized rabbits have the ability to activate AT2R and counteract the AT1R-mediated vasoconstriction. These autoantibodies provide useful and selective tools for the study of their roles in blood pressure regulation and possible therapeutic intervention. PMID:26259590

  9. Decrease in TSH Receptor Autoantibodies during Antithyroid Treatment

    DEFF Research Database (Denmark)

    Christensen, Niels Juel; Habekost, Gurli; Bratholm, Palle

    2011-01-01

    We have previously shown that a long noncoding RNA transcript Heg is negatively correlated with TSH receptor autoantibodies (TRAb) in patients with untreated Graves' disease and with CD14 mRNA in treated patients and controls. Thus patients with high concentrations of Heg RNA have low levels of...... influence the level of TSH receptor autoantibodies but by different mechanisms....

  10. 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)....

  11. How Relevant Are GFAP Autoantibodies in Autism and Tourette Syndrome?

    Science.gov (United States)

    Kirkman, Nikki J.; Libbey, Jane E.; Sweeten, Thayne L.; Coon, Hilary H.; Miller, Judith N.; Stevenson, Edward K.; Lainhart, Janet E.; McMahon, William M.; Fujinami, Robert S.

    2008-01-01

    Controversy exists over the role of autoantibodies to central nervous system antigens in autism and Tourette Syndrome. We investigated plasma autoantibody titers to glial fibrillary acidic protein (GFAP) in children with classic onset (33) and regressive onset (26) autism, controls (25, healthy age- and gender-matched) and individuals with…

  12. 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

  13. Biological variation of thyroid autoantibodies and thyroglobulin

    DEFF Research Database (Denmark)

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

    2007-01-01

    BACKGROUND: It has been shown that the level of serum thyroid antibodies affects serum thyrotropin (TSH) concentrations in men and women, and that these autoantibodies in combination with serum TSH are predictive of future thyroid disease. As the biological variation of these autoantibodies 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...... 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...

  14. Autoantibody recognition mechanisms of p53 epitopes

    Science.gov (United States)

    Phillips, J. C.

    2016-06-01

    There is an urgent need for economical blood based, noninvasive molecular biomarkers to assist in the detection and diagnosis of cancers in a cost-effective manner at an early stage, when curative interventions are still possible. Serum autoantibodies are attractive biomarkers for early cancer detection, but their development has been hindered by the punctuated genetic nature of the ten million known cancer mutations. A landmark study of 50,000 patients (Pedersen et al., 2013) showed that a few p53 15-mer epitopes are much more sensitive colon cancer biomarkers than p53, which in turn is a more sensitive cancer biomarker than any other protein. The function of p53 as a nearly universal "tumor suppressor" is well established, because of its strong immunogenicity in terms of not only antibody recruitment, but also stimulation of autoantibodies. Here we examine dimensionally compressed bioinformatic fractal scaling analysis for identifying the few sensitive epitopes from the p53 amino acid sequence, and show how it could be used for early cancer detection (ECD). We trim 15-mers to 7-mers, and identify specific 7-mers from other species that could be more sensitive to aggressive human cancers, such as liver cancer. Our results could provide a roadmap for ECD.

  15. Multiparametric detection of autoantibodies in systemic lupus erythematosus.

    Science.gov (United States)

    Budde, P; Zucht, H-D; Vordenbäumen, S; Goehler, H; Fischer-Betz, R; Gamer, M; Marquart, K; Rengers, P; Richter, J; Lueking, A; Schulz-Knappe, P; Schneider, M

    2016-07-01

    Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease manifestations, disease progression and treatment response. Therefore, strategies to identify biomarkers that help distinguishing SLE subgroups are a major focus of biomarker research. We reasoned that a multiparametric autoantibody profiling approach combined with data mining tools could be applied to identify SLE patient clusters. We used a bead-based array containing 86 antigens including diverse nuclear and immune defense pathway proteins. Sixty-four autoantibodies were significantly (p < 0.05) increased in SLE (n = 69) compared to healthy controls (HC, n = 59). Using binary cut-off thresholds (95% quantile of HC), hierarchical clustering of SLE patients yields five clusters, which differ qualitatively and in their total number of autoantibodies. In two patient clusters the overall accumulated autoantibody reactivity of all antigens tested was 31% and 48%, respectively. We observed a positive association between the autoantibody signature present in these two patient clusters and the clinical manifestation of glomerulonephritis (GLMN). In addition, groups of autoantibodies directed against distinct intracellular compartments and/or biological motifs characterize the different SLE subgroups. Our findings highlight the relevant potential of multiparametric autoantibody detection and may contribute to a deeper understanding of the clinical and serological diversity of SLE. PMID:27252257

  16. Pemphigus vulgaris autoantibody profiling by proteomic technique.

    Directory of Open Access Journals (Sweden)

    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.

  17. [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. PMID:24139501

  18. 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.

  19. 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 (mainl

  20. Human autoantibodies against desmosomes: possible causative factors in pemphigus.

    OpenAIRE

    Jones, J. C.; Arnn, J; Staehelin, L A; Goldman, R D

    1984-01-01

    Pemphigus is a human disease that causes extensive blistering of the skin. This blistering is related to a loss of epidermal cell cohesion and is accompanied by circulating autoantibodies that stain epidermal cell surfaces, as shown by immunofluorescence microscopy. One of the major components involved in epidermal cell cohesion is the desmosome. The pathological changes that accompany pemphigus led us to determine whether the autoantibodies are specific for desmosomes. Incubation of cultured...

  1. Autoantibody recognition of collagen type II in arthritis

    OpenAIRE

    Lindh, Ingrid

    2013-01-01

    Autoantibodies against collagen type II (CII), a protein localized in the joint cartilage, play a major role in collagen-induced arthritis (CIA), one of the most commonly used animal models for rheumatoid arthritis (RA). The studies included in this thesis were undertaken to elucidate structural and functional requirements for B and T cells to recognize native CII structures during experimental arthritis as well as in human RA. To reveal in detail how CII-specific autoantibodies recognize CII...

  2. The neuropeptide neuromedin U promotes autoantibody-mediated arthritis

    OpenAIRE

    Rao, Sindhuja M; Auger, Jennifer L; Gaillard, Philippe; Wada, Etsuko; Kojima, Masayasu; Binstadt, Bryce A; Weissleder, Ralph; Torres, Richard; Benoist, Christophe O.; Mathis, Diane J.

    2012-01-01

    Introduction: Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects. Methods: Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU def...

  3. Clinical Significance of Serum Autoantibodies in Idiopathic Interstitial Pneumonia

    OpenAIRE

    Kang, Bo Hyoung; Park, Jin Kyeong; Roh, Jae Hyung; Song, Jin Woo; Lee, Chang Keun; Kim, Miyoung; Jang, Se Jin; Colby, Thomas V.; Kim, Dong Soon

    2013-01-01

    Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary ...

  4. Chronic idiopathic urticaria with functional autoantibodies: 12 years on.

    Science.gov (United States)

    Sabroe, R A; Greaves, M W

    2006-05-01

    It is now recognized that approximately one-third of patients with chronic idiopathic urticaria (CIU) have histamine-releasing autoantibodies directed against either the high-affinity IgE receptor or, less frequently, against IgE. However, there are several unsolved problems relating to the role of such autoantibodies in the disease. Additionally, it is not clear whether CIU with autoantibodies can be classified as an autoimmune disease. The detection of patients with autoantibodies also poses challenges. Firstly, the only in vivo method, the autologous serum skin test, is at best 80% sensitive and specific using in vitro basophil histamine release assays as the verum. Secondly, in vitro tests are only done in a small number of research laboratories, and are not widely commercially available, and thirdly, there is some divergence between results obtained by different methods (functional and immunoassays) used to detect patients with autoantibodies. The presence of autoantibodies may be important clinically in a small group of severely affected, treatment-resistant patients, where immunomodulatory treatments may be helpful. PMID:16634880

  5. Neuronal autoantibodies in patients with Rasmussen's encephalitis.

    Science.gov (United States)

    Samanci, Bedia; Tektürk, Pınar; Tüzün, Erdem; Erdağ, Ece; Kınay, Demet; Yapıcı, Zuhal; Baykan, Betül

    2016-06-01

    Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti-neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell-based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. The mean age at onset of seizures was 8.3±3.4 years (range: 4-13.5) and mean follow-up time was 11.2±5.4 years (range: 5-19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen-specific anti-neuronal autoimmunity in RE pathophysiology. PMID:27248684

  6. The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas : are autoantibodies of influence?

    NARCIS (Netherlands)

    Lo Galbo, Annalisa M.; De Bree, Remco; Kuik, Dirk J.; Lips, Paul Th. A. M.; Von Blomberg, B. Mary E.; Langendijk, Johannes A.; Leemans, C. Rene

    2007-01-01

    Conclusions. The incidence rate of hypothyroidism after treatment for laryngeal and hypopharyngeal cancer is high, especially after combination treatment. An association between hypothyroidism and autoantibodies was found. Objectives. The incidences of hypothyroidism and autoantibodies were assessed

  7. Autoantibodies in chronic hepatitis C: A clinical perspective

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Non-organ-specific autoantibodies and thyroid autoantibodieshave been frequently found in chroniccarriers of hepatitis C virus (HCV). With respect toendomysial antibodies and tissue transglutaminase,it is controversial whether the prevalence of glutenrelatedseromarkers is higher in patients with HCV. Insuch cases, in addition to acknowledging any currentlyexisting autoimmune disease, recognizing the risk ofthe patient developing an autoimmune disease duringinterferon (IFN)-based treatment must be a principleconcern. From a clinical point-of-view, the presence ofautoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbasedHCV treatment. In this paper, we review theprevalence of autoantibodies in individuals with hepatitisC, the clinical significance of these autoantibodies, andthe approach recommended for such situations.

  8. Auto-antibodies and seizures: clinical and EEG findings.

    Science.gov (United States)

    Drazkowski, Joseph; Hoerth, Matthew; Tapsell, Lisa; Noe, Katherine; Shih, Jerry; Sirven, Joseph; Tatum, William O

    2014-03-01

    Epilepsy is a common disorder that may be caused by wide ranging etiologies. Historically a significant number of people with epilepsy have idiopathic epilepsy without a definitive etiology. More recently, auto-antibodies have been discovered to be associated with numerous conditions affecting the nervous system, including epilepsy. With this increased understanding of the potential for immune-based etiologies for epilepsy it is important to recognize the associated EEG patterns in such cases. This report presents the EEG findings in epilepsy patients with one or more auto-antibodies. PMID:24783749

  9. Repertoire cloning of lupus anti-DNA autoantibodies.

    OpenAIRE

    Roben, P; Barbas, S M; Sandoval, L; Lecerf, J M; Stollar, B D; Solomon, A; Silverman, G J

    1996-01-01

    To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-double-stranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These i...

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

    Directory of Open Access Journals (Sweden)

    C. Poggialini

    2014-02-01

    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.

  11. Characterization of Polyclonal Antibody Induced by Autoantibody TPO (Thyroidperoxidase) From Autoimmune Thyroid Disease (AITD) Serum with ELISA and Western Blotting

    OpenAIRE

    Maulidya Aulia Fiqriyana; Aulanni'am Aulanni'am; Anna Roosdiana

    2013-01-01

    Autoantibody TPO is a potential marker for early detection of autoimmune thyroid disease (AITD). Autoantibody TPO has a specifity and a sensitivity ranging from 82% to100% in comparison to other AITD serology markers. Concentration of autoantibody TPO in sera had a positive correlation with activities of chronic AITD. This research have been conducted to investigate the characteristic of polyclonal antibody TPO induced by autoantibody TPO from serum of AITD patients. The autoantibody TPO was ...

  12. Toward a new autoantibody diagnostic orthodoxy: understanding the bad, good and indifferent.

    Science.gov (United States)

    Fritzler, Marvin J

    2012-08-01

    Rapid advances in diagnostic technologies used to detect autoantibodies have made it difficult for even the most modern laboratory to keep abreast of the changing approaches and platforms, not to mention the clinicians who are hard pressed to keep abreast of evolving diagnostic paradigms attended by these newer techniques. While autoantibody testing is traditionally considered to be primarily serving the realm of diagnostic medicine, there is little doubt that autoantibodies are also being recognized as an approach to providing prognostic and therapeutic information. Accordingly, along with related proteomics, genomics and metabolomics, it is taking on increasing importance in the realm of personalized medicine. In today's world of autoantibody diagnostics, overarching concerns about false-negative and false-positive autoantibodies tests cannot be summarily dismissed by citing pros or cons of any one technology or diagnostic platform, but often point to persisting gaps in our knowledge about, and understanding of, the origin and roles of autoantibodies. Before we can hope to completely understand the enigmas that attend the results of autoantibody diagnostic tests, perhaps it is time to step back and re-examine long-accepted paradigms and beliefs. This review will address some of the issues that impact on autoantibody detection technologies and some of the considerations and issues that will attend a new orthodoxy of autoantibody diagnostics. These issues will be addressed in the context of "bad" (pathogenic), "good" (protective) or "indifferent" (no apparent role in disease) autoantibodies. PMID:26000127

  13. Autoantibody profile in individuals with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Maíra Luciana Marconcini

    2013-04-01

    Full Text Available Introduction Autoantibodies are often produced during infection with chronic hepatitis C virus (HCV, but it remains controversial whether they influence the biochemical profile and histological features of this disease. Therefore, this current study sought to describe these autoantibodies and evaluate their impact on the clinical and histological presentation of hepatitis C. Methods This cross-sectional analytical study assessed patients with HCV (RNA+ from October 2011 to July 2012. Results This study included 66 patients, with a mean age of 53.2±10.5 years. Of these patients, 60.6% were male, and 54.3% presented with genotype 1. Non-organ-specific autoantibodies (NOSA were detected in 24% of the patients; of these, 7.6% were anti-mitochondrial antibodies (AMA+, 26.7% were anti-smooth muscle antibodies (SMA+ and 6.8% were liver kidney microsomal type 1 antibodies (LKM1+. With respect to the thyroid autoantibodies, 7.4% were anti-peroxidase (ATPO+ antibodies, and none were anti-thyroglobulin (ATG+ antibodies. Regarding celiac disease autoantibodies, 5.8% were endomysial antibodies (EMA+, and no transglutaminase (TTG+ antibodies were detected. Cryoglobulins were found in 2.1% of patients. When NOSA+ individuals were compared to patients without the presence of NOSAs, they exhibited higher median alkaline phosphatase (0.7 vs. 0.6 xULN; p=0.041, lower median platelet counts (141,500.0 vs. 180,500.0/mm 3 ; p=0.036, lower mean prothrombin activity (72.6±11.5% vs. 82.2±16.0%; p=0.012 and an increased prevalence of significant fibrosis (E≥2 (45.5% vs. 18.2%; p=0.012. There was also a tendency for a greater proportion of NOSA+ cases to have marked periportal activity (APP≥3 (44.5% vs. 15.6%; p=0.087. Conclusions In addition to the high prevalence of autoantibodies associated with HCV infection, it was observed that NOSA positivity was associated with a more severe histological and biochemical profile of hepatitis C infection.

  14. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis.

    OpenAIRE

    Jennette, J C; Wilkman, A. S.; Falk, R J

    1989-01-01

    Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patient...

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

    OpenAIRE

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

    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 ...

  16. Pathogenicity of Autoantibodies in Anti-p200 Pemphigoid

    Science.gov (United States)

    Beckmann, Tina; Hirose, Misa; Dworschak, Jenny; Recke, Andreas; Ludwig, Ralf J.; Hashimoto, Takashi; Zillikens, Detlef; Schmidt, Enno

    2012-01-01

    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. PMID:22911854

  17. 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.

  18. Primary biliary cirrhosis:What do autoantibodies tell us?

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antim...

  19. Human autoantibodies against a desmosomal core protein in pemphigus foliaceus

    OpenAIRE

    1984-01-01

    Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and electron microscopy of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament- desmosome complex. In this study we demonstrate that autoantibodies from certain PF patients bin...

  20. Characterization Analysis of Human Anti-Ferritin Autoantibodies

    OpenAIRE

    Shusaku Higashi; Kosei Nagasawa; Yasunaga Yoshikawa; Kiyotaka Watanabe; Koichi Orino

    2014-01-01

    Anti-ferritin autoantibodies are found in many animals. Human ferritin-binding proteins (FBPs) were partially purified from human serum by ion-exchange chromatography and immobilized metal affinity chromatography with Zn2+. Crude FBPs were immunocoprecipitated with canine liver ferritin followed by the addition of anti-ferritin antibodies. Immunoglobulins in the immunocoprecipitate were detected with antibodies specific for human IgG, IgM or IgA heavy chains, and immunoglobulins IgG, IgM and ...

  1. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    OpenAIRE

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

    2010-01-01

    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 comp...

  2. 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.

  3. 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.

  4. Control of autoantibody affinity by selection against amino acid replacements in the complementarity-determining regions.

    OpenAIRE

    Børretzen, M; Randen, I; Zdárský, E; Førre, O; Natvig, J B; Thompson, K M

    1994-01-01

    Rheumatoid factor (RF) autoantibodies can be produced in healthy individuals after infections or immunizations and thus escape normal tolerization mechanisms. It has not been clear whether such autoantibodies can undergo somatic hypermutation and affinity maturation similar to antibodies to exogenous antigens. We have investigated how these autoantibodies are regulated in normal individuals by analyzing the sequences of monoclonal IgM RFs obtained as hybridomas from donors after immunization....

  5. Disseminated Talaromyces marneffei and Mycobacterium abscessus in a Patient With Anti-Interferon-γ Autoantibodies.

    Science.gov (United States)

    Pruetpongpun, Nattapol; Khawcharoenporn, Thana; Damronglerd, Pansachee; Suthiwartnarueput, Worapop; Apisarnthanarak, Anucha; Rujanavej, Sasinuch; Suwantarat, Nuntra

    2016-04-01

    Anti-interferon (IFN)-γ autoantibodies are increasingly recognized as a cause of adult-onset immunodeficiency and increased risk for infections with intracellular pathogens. We report on disseminated Talaromyces (Penicillium) marneffei and Mycobacterium abscessus infection in a 72-year-old, human immunodeficiency virus noninfected, Thai man with anti-IFN-γ autoantibody. The patient was successfully treated with antimicrobial therapy and rituximab to control B cell-derived autoantibodies. PMID:27419165

  6. Role of Natural Autoantibodies in Ugandans With Rheumatic Heart Disease and HIV

    Directory of Open Access Journals (Sweden)

    Daniel M. Huck

    2016-03-01

    Interpretation: We found that HIV and RHD are associated with alterations in natural autoantibody responses previously linked to an increased risk for atherosclerosis and autoimmune inflammatory disease.

  7. Genetic Complementation Results in Augmented Autoantibody Responses to Lupus-Associated Antigens

    OpenAIRE

    Sim, Davis L; Bagavant, Harini; Scindia, Yogesh M; Ge, Yan; Gaskin, Felicia; Fu, Shu Man; Deshmukh, Umesh S.

    2009-01-01

    Lupus-prone female NZM2328 mice develop high titers of anti-nuclear and anti-dsDNA autoantibodies. Despite high expression of type I IFNs, these mice do not develop autoantibodies to the small nuclear ribonucleoprotein (snRNP) complex. Thus, additional genetic factors must regulate the generation of anti-snRNP autoantibodies. In contrast, despite much lower expression of type 1 IFNs, the diabetes-prone NOD mice spontaneously make anti-snRNP autoantibodies, albeit at a low incidence. To determ...

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Xufei Zhang

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

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

    DEFF Research Database (Denmark)

    Graudal, N A; Svenson, M; Tarp, Ulrik; Garred, P; Jurik, Anne Grethe; Bendtzen, K

    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)....

  11. Does the autoantibody immunodominant region on thyroid peroxidase include amino acid residues 742-771?

    Science.gov (United States)

    Xiong, Z; Farilla, L; Guo, J; McLachlan, S; Rapoport, B

    2001-03-01

    Identification of the thyroid peroxidase (TPO) amino acid residues that comprise the autoantibody immunodominant region is an important goal that has proven difficult because of the conformational nature of the epitopes involved. Recent data suggest that the immunodominant region has been located. Thus, by autoantibody recognition of tryptic fragments of native TPO, as well as of conformational portions of TPO expressed as cell-free translates, the autoantibody immunodominant region appears to include amino acid residues 742-771, near the C terminus of the ectodomain. To evaluate this deduction, we expressed as cell-free translates the full TPO ectodomain, as well as TPO truncated after residues 741 and 771. The epitopic integrity of these molecules was first confirmed by immunoprecipitation by patient sera containing TPO autoantibodies. However, autoantibody recognition could involve a minority of TPO autoantibodies with the individual sera, not fulfilling the strict criteria for immunodominance. In order to obtain definitive data, we performed immunoprecipitations on these TPO variants with four recombinant human monoclonal autoantibodies that define the immunodominant region. All four monoclonal autoantibodies immunoprecipitated TPO 1-741 to the same extent as they did TPO 1-771 and the full TPO ectodomain, indicating that the immunodominant region comprises (at least in large part) amino acid residues upstream of residue 741. PMID:11327613

  12. Autoantibodies to ribonucleoprotein particles containing U2 small nuclear RNA.

    OpenAIRE

    Habets, W; Hoet, M; Bringmann, P; Lührmann, R; van Venrooij, W

    1985-01-01

    Autoantibodies exclusively precipitating U1 and U2 small nuclear ribonucleoprotein (snRNP) particles [anti-(U1,U2)RNP] were detected in sera from four patients with autoimmune disorders. When tested by immunoblotting, these sera recognized up to four different protein antigens in purified mixtures of U1-U6 RNP particles. With purified antibody fractions eluted from individual antigen bands on nitrocellulose blots, each anti-(U1,U2)RNP serum precipitated U2 RNP by virtue of the recognition of ...

  13. Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus

    Science.gov (United States)

    Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.

    2016-06-01

    High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.

  14. 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; Jørgensen, Torben; Perrild, Hans; Ovesen, Lars; Rasmussen, Lone Banke

    2008-01-01

    Background: Autoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid......: Smoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies....

  15. 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.

  16. Evaluation of a radioreceptor assay for TSH receptor autoantibodies

    Energy Technology Data Exchange (ETDEWEB)

    Rootwelt, K.

    1988-02-01

    A commercial radioreceptor assay for TSH receptor autoantibodies (TRAb), based on solubilized porcine receptor and purified radio-iodinated bovine TSH, was tested in 264 subjects with a variety of thyroid disorders. The sensitivity of the assay for the detection of hyperthyroid Graves' disease was 91%. The assay specificity for Graves' disease was 95%. With the exception of one patient with Hashimoto's disease and one patient with de Quervain's subacute thyroiditis no subjects other than Graves' patients had detectable TRAb. Thus purely blocking TSII receptor autoantibodies were not detected with the assay. One female with thyroxine-treated idiopathic primary hypothyroidism who had given birth to two children with transiently elevated TSH, was found to have a circulating TSH-binding substance that resulted in an abnormally negative TRAb value, and highly discrepant results when TSH was measured with a double antibody TSH radioimmunoassay and an immunoradiometric assay. The TSH-binding substance was precipitated like a protein, but was not IgG. Similar findings have not previously been reported.

  17. Possible enhancement of BP180 autoantibody production by herpes zoster.

    Science.gov (United States)

    Kamiya, Koji; Aoyama, Yumi; Suzuki, Takahiro; Niwa, Haruo; Horio, Ai; Nishio, Eiichi; Tokura, Yoshiki

    2016-02-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies against type XVII collagen/BP180 (BP180). Although the mechanisms of autoantibody production remain to be elucidated, herpes virus infections have been identified as a possible triggering factor for pemphigus. We report a case of herpes zoster (HZ) having anti-BP180 serum antibodies. The patient developed sudden-onset, tense blisters and edematous erythema on the right anterior chest, shoulder and upper back. Histopathology showed remarkable degeneration of keratinocytes, acantholysis and blister formation with ballooning cells, indicating herpes virus infection. A polymerase chain reaction analysis of varicella zoster virus (VZV) was positive in crusts and effusions from the skin lesions, confirming the definitive diagnosis of HZ. Notably, we found that the patient had anti-BP180 serum antibodies in association with the occurrence of HZ. After successful treatment with valacyclovir hydrochloride for 7 days, the serum levels of anti-BP180 antibodies decreased in accordance with the improvement of skin lesions. These findings suggest that the production of anti-BP180 antibodies could be triggered by the reactivation of VZV. PMID:26212492

  18. Evaluation of a radioreceptor assay for TSH receptor autoantibodies

    International Nuclear Information System (INIS)

    A commercial radioreceptor assay for TSH receptor autoantibodies (TRAb), based on solubilized porcine receptor and purified radio-iodinated bovine TSH, was tested in 264 subjects with a variety of thyroid disorders. The sensitivity of the assay for the detection of hyperthyroid Graves' disease was 91%. The assay specificity for Graves' disease was 95%. With the exception of one patient with Hashimoto's disease and one patient with de Quervain's subacute thyroiditis no subjects other than Graves' patients had detectable TRAb. Thus purely blocking TSII receptor autoantibodies were not detected with the assay. One female with thyroxine-treated idiopathic primary hypothyroidism who had given birth to two children with transiently elevated TSH, was found to have a circulating TSH-binding substance that resulted in an abnormally negative TRAb value, and highly discrepant results when TSH was measured with a double antibody TSH radioimmunoassay and an immunoradiometric assay. The TSH-binding substance was precipitated like a protein, but was not IgG. Similar findings have not previously been reported. (author)

  19. Myasthenia gravis - autoantibody characteristics and their implications for therapy.

    Science.gov (United States)

    Gilhus, Nils Erik; Skeie, Geir Olve; Romi, Fredrik; Lazaridis, Konstantinos; Zisimopoulou, Paraskevi; Tzartos, Socrates

    2016-05-01

    Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that target the neuromuscular junction, leading to muscle weakness and fatigability. Currently available treatments for the disease include symptomatic pharmacological treatment, immunomodulatory drugs, plasma exchange, thymectomy and supportive therapies. Different autoantibody patterns and clinical manifestations characterize different subgroups of the disease: early-onset MG, late-onset MG, thymoma MG, muscle-specific kinase MG, low-density lipoprotein receptor-related protein 4 MG, seronegative MG, and ocular MG. These subtypes differ in terms of clinical characteristics, disease pathogenesis, prognosis and response to therapies. Patients would, therefore, benefit from treatment that is tailored to their disease subgroup, as well as other possible disease biomarkers, such as antibodies against cytoplasmic muscle proteins. Here, we discuss the different MG subtypes, the sensitivity and specificity of the various antibodies involved in MG for distinguishing between these subtypes, and the value of antibody assays in guiding optimal therapy. An understanding of these elements should be useful in determining how to adapt existing therapies to the requirements of each patient. PMID:27103470

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

    International Nuclear Information System (INIS)

    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. 125I-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 125I-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

  1. Immunospecific red cell binding of iodine /sup 125/-labeled immunoglobulin G erythrocyte autoantibodies

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-09-01

    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 /sup 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. /sup 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 /sup 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.

  2. Role of autoantibodies against the linker subdomains of envoplakin and periplakin in the pathogenesis of paraneoplastic pemphigus

    Institute of Scientific and Technical Information of China (English)

    LI Jing; BU Ding-fang; HUANG Yong-chu; ZHU Xue-jun

    2009-01-01

    Background The presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus (PNP). Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris (PV), has been proved pathogenic in PNP. Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNP. Envoplakin (EPL) and periplakin (PPL) are recognized by most PNP sere. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments.Methods We characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients' sera and their associated tumors by enzyme-linked immunosorbent assay (ELISA) and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes (HEK), to evaluate the changes of cell-cell adhesion.Results Autoantibodies against EPL and PPL were detected in most PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sere were capable of dissociating cultured human epidermal keratinocytes.Conclusion Autoantibodies against EPL and PPL may also be pathogenic in PNP.

  3. The patent situation concerning the treatment of diseases associated with autoantibodies directed against G-protein-coupled receptors.

    Science.gov (United States)

    Haberland, Annekathrin; Wallukat, Gerd; Schimke, Ingolf

    2013-03-01

    Agonist-like autoantibodies against receptors of the G-protein-coupled signal cascade have been identified as the pathogenic principle for a variety of diseases, especially those of the heart and vascular system. Consequently, the elimination or neutralization of such autoantibodies is an advised goal for causal therapeutic intervention. This article provides a short, noncomplete overview about remarkable developmental strategies and technical solutions for the therapy of diseases, associated with G-protein-coupled receptor autoantibodies. According to the immunoglobulin nature of the therapeutic target, several strategies are possible, such as the use of the autoantibody epitope sequences as competitors or binding molecules for specific autoantibody-elimination by apheresis. Complete immunoglobulin elimination, as is currently being tested in autoantibody-positive cardiomyopathy patients, would be a nonspecific solution as would the use of immunosuppressant agents. The use of autoantibody-binding molecules on an aptamer basis for neutralization or elimination is a newly developed specific therapeutic option. PMID:24237028

  4. 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. PMID:27255734

  5. Effect of superposition and masking between red blood cell autoantibodies and alloantibodies.

    Science.gov (United States)

    Yu, Y; Wang, D Q

    2014-01-01

    This study aimed to explore the law of superposition and masking between autoantibodies and alloantibodies, and to ensure the detection of alloantibodies and to improve the safety of warm autoimmune hemolytic anemia patients. Eight kinds of commercial IgG red blood cell antibody reagents were serially diluted, and 3 kinds of antibodies at dilutions showing a continuous gradual decline in agglutination strength with the corresponding antigen red blood cells were treated as the target antibodies. Anti-D and anti-M were treated as simulated autoantibodies, and anti-Fya was treated as a simulated alloantibody. Four concentrations, 4+, 3+, 2+ and 1+, of autoantibodies and three concentrations, 3+, 2+ and 1+, of alloantibodies were combined, and 12 kinds of hybrid antibodies were detected and evaluated by the anti-human globulin micro-column gel assay. When the simulated strong autoantibody (4+) was used, the alloantibodies (3+, 2+, 1+) had no effect on the final agglutination strength; when the strength of agglutination produced by the simulated autoantibody was less than 4+, and at the same time there were alloantibodies (3+, 2+, 1+), the differences in agglutination strength with a panel of RBCs could be clearly observed. Strong autoantibodies (4+) can exert a masking effect, leading to alloantibodies being undetected; autoantibodies less than 4+, will produce the superimposed effect with alloantibodies, resulting in differences in agglutination strength. PMID:25036516

  6. Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer

    Science.gov (United States)

    Werner, Simone; Chen, Hongda; Butt, Julia; Michel, Angelika; Knebel, Phillip; Holleczek, Bernd; Zörnig, Inka; Eichmüller, Stefan B.; Jäger, Dirk; Pawlita, Michael; Waterboer, Tim; Brenner, Hermann

    2016-01-01

    Autoantibodies against tumor-associated antigens (TAAs) have been suggested as biomarkers for early detection of gastric cancer. However, studies that systematically assess the diagnostic performance of a large number of autoantibodies are rare. Here, we used bead-based multiplex serology to simultaneously measure autoantibody responses against 64 candidate TAAs in serum samples from 329 gastric cancer patients, 321 healthy controls and 124 participants with other diseases of the upper digestive tract. At 98% specificity, sensitivities for the 64 tested autoantibodies ranged from 0–12% in the training set and a combination of autoantibodies against five TAAs (MAGEA4 + CTAG1 + TP53 + ERBB2_C + SDCCAG8) was able to detect 32% of the gastric cancer patients at a specificity of 87% in the validation set. Sensitivities for early and late stage gastric cancers were similar, while chronic atrophic gastritis, a precursor lesion of gastric cancer, was not detectable. However, the 5-marker combination also detected 26% of the esophageal cancer patients. In conclusion, the tested autoantibodies and combinations alone did not reach sufficient sensitivity for gastric cancer screening. Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers. PMID:27140836

  7. Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer.

    Science.gov (United States)

    Werner, Simone; Chen, Hongda; Butt, Julia; Michel, Angelika; Knebel, Phillip; Holleczek, Bernd; Zörnig, Inka; Eichmüller, Stefan B; Jäger, Dirk; Pawlita, Michael; Waterboer, Tim; Brenner, Hermann

    2016-01-01

    Autoantibodies against tumor-associated antigens (TAAs) have been suggested as biomarkers for early detection of gastric cancer. However, studies that systematically assess the diagnostic performance of a large number of autoantibodies are rare. Here, we used bead-based multiplex serology to simultaneously measure autoantibody responses against 64 candidate TAAs in serum samples from 329 gastric cancer patients, 321 healthy controls and 124 participants with other diseases of the upper digestive tract. At 98% specificity, sensitivities for the 64 tested autoantibodies ranged from 0-12% in the training set and a combination of autoantibodies against five TAAs (MAGEA4 + CTAG1 + TP53 + ERBB2_C + SDCCAG8) was able to detect 32% of the gastric cancer patients at a specificity of 87% in the validation set. Sensitivities for early and late stage gastric cancers were similar, while chronic atrophic gastritis, a precursor lesion of gastric cancer, was not detectable. However, the 5-marker combination also detected 26% of the esophageal cancer patients. In conclusion, the tested autoantibodies and combinations alone did not reach sufficient sensitivity for gastric cancer screening. Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers. PMID:27140836

  8. Development of a radioimmunoassay for autoantibodies to thyroid peroxidase (TPO) in human serum

    International Nuclear Information System (INIS)

    Purpose: Autoantibodies to thyroid peroxidase (TPO), the thyroid 'microsomal' antigen, are widely utilized in the diagnosis of human autoimmune thyroid disease. The purpose of our work is to develop a useful radioimmunoassay for large scale routine measurement of autoantibodies to TPO in human serum. Methods: the assay is based on autoantibody inhibition of binding of 125I-labeled TPO to an anti-TPO monoclonal antibody coupled with poly-acrylamide macroparticles. Standards containing anti-TPO monoclonal antibody were employed. Serum samples of known anti-TPO body positive (n=38) and negative(n=55) were measured by the new assay. To evaluate the specificity of the assay, several serum samples with high concentration of anti-thyroglobulin (Tg) autoantibody were measured again following absorption with thyroglobulin. Results: Unlike most of other immunoassay for anti-TPO autoantibodies, the new assay has no need for sample dilution. The detection limit of the new assay was 4.4 U/ml and the within-and between assay coefficients of variation (CVs) ranged from 4.7% to 9.8% and from 9.4% to 14.4% respectively. No influence of anti-Tg autoantibodies on the assay was observed. The value for the samples of known autoantibodies to TPO positive or negative were ranging from 12.6 to more than 3000 U/ml and from to 8.1 U/ml respectively. Conclusion: This new assay is sensitive, not affected by anti-thyroglobulin autoantibodies, easy to perform and has no need for sample dilution. Therefore, it is applicable for large-scale routine measurement of autoantibodies to TPO. (authors)

  9. A COMPLEX OF INTERMEDIATE FILAMENT PROTEIN-DNA: A TARGET FOR AUTOANTIBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS?

    Institute of Scientific and Technical Information of China (English)

    阎锡德; S.Kuhn; P.Traub

    1995-01-01

    Autoantibodies in systemic lupus erythematosus which cross-react with double stranded DNA and in-termediate filament proteins are frequently reported.However,little is Known about the origin and the target of these antibodies.In this paper,a polyspecific monoclonal antibody,XY12,produced by the im-munization of genetically non-autoimmune mice with a DNA-protein complex is detsiled.Its antigen bind-ing patterms are very similar to the autoantibodies.The data suggest that these autoantibodies may be trig-gered by a circulating nucleoprotein.

  10. [Pulmonary autoantibodies in bronchial asthma patients undergoing cave and climate therapy in Bystrá].

    Science.gov (United States)

    Pasková, S; Kolesár, J; Siposová, E

    1976-01-01

    Pulmonary autoantibodies were determined by us in the sera of 37 patients who underwent a 6-week speleo- and climatotherapy in the cave of Bystrá. The titres found in both groups of patients showed no difference. Global evaluation revealed a high incidence of pulmonary autoantibodies. We saw a direct relationship between the titre and the degree of severity of the disease or the clinical condition. The demonstration of circulating pulmonary autoantibodies in bronchial asthma is possibly not only of diagnostic value but also of prognostic importance. PMID:135497

  11. 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; Østergaard, Birthe; Brandslund, Ivan

    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...... hypothesised that autoantibodies against HER2 might have a stimulatory capacity and could be the cause of the HER2 gene amplification phenomenon. To investigate this, we developed a test for the detection of autoantibodies against HER2 in serum (S-HER2Ab)....

  12. [Novel autoantibodies in inflammatory myopathies and systemic sclerosis].

    Science.gov (United States)

    Ribi, Camillo

    2015-01-14

    Acquired inflammatory myopathies and systemic sclerosis are chronic autoimmune conditions. These diseases arise from sustained activation of the innate and adaptive immune system, resulting in damage to blood vessels, muscles, connective tissues and internal organs. Auto-antibodies are found in a majority of cases, which makes the immune serology an important diagnostic tool. The immuno dot assays detect a variety of disease-specific-or-associated antibodies. A positive result should be correlated with the indirect immunofluorescence pattern of the antinuclear antibody screen. Some antibodies are associated with specific organ involvement, other may indicated an underlying neoplastic condition. The scope of this article is to review the diagnostic and prognostic value of antibodies in inflammatory myopathies and systemic sclerosis. PMID:25799647

  13. Determination of autoantibodies to annexin XI in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Jorgensen, C S; Levantino, G; Houen, Gunnar;

    2000-01-01

    Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA...... experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out of...... 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...

  14. [Juvenile dermatomyositis and new autoantibodies: Cases and review].

    Science.gov (United States)

    Guarella, M; Jurquet, A-L; Retornaz, K; Bardin, N; Chastang, M-C; Desjonquere, M; Fabien, N; Belot, A

    2015-12-01

    Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children. Its diagnosis is usually made on a clinical basis following the criteria of Bohan and Peter (1975). Recently, the presence of myositis-specific autoantibodies (MSAs) have started to be associated with specific outcome in adult patients; the diagnosis and prognosis value of these autoantibodies remains to be identified in children. We report four cases of JDM with MSAs focusing on clinical, biological, and radiological manifestations, and then we describe associated treatment. The cohort comprises four girls with an average age of 8.5 years. The time to diagnosis was 1 week to 4 months. For these patients, the immunologic study found one patient positive for the MDA5 antibody (or CADM 140), one positive for the TIF1γ antibody (or p155/140), and two patients positive for the NXP2 antibody (or p140/MJ). Each patient showed specific and characteristic cutaneous manifestations. For example, the girl positive for the TIF1γ antibody presented the most severe skin disease with urticaria, face edema, and vascularity of the neck and shoulders. However, regarding muscular features, proximal weakness was present in most of the cohort, except for the child positive for the MDA5 antibody, who presented no sign of muscular disease at the beginning with low CK levels. Importantly, acute pancreatitis also affected this patient. Concerning radiological indications, muscular MRI evidenced hyperinflammation, a sign of diffuse myositis, in all these patients. Treatments consisted in corticosteroids together with methotrexate or mycofenolate mofetil associated or not with intravenous immunoglobulin therapy. This report highlights the importance of systematic detection and analysis of MSA in diagnosis and characterization of JDM, and describes a new approach that would allow more focused treatments and be a useful predictor of clinical complications and prognosis in JDM-affected subjects. PMID:26598044

  15. The Prevalence of Celiac Autoantibodies in Hepatitis Patients

    Directory of Open Access Journals (Sweden)

    Hamidreza Sima

    2010-09-01

    Full Text Available Celiac disease has been associated with other autoimmune disorders such as autoimmune hepatitis, moreover it is known that T cell mediated immune response to dietary gluten and released cytokines are important for the entheropathy seen in celiac disease. We investigated celiac autoantibodies in patients with autoimmune hepatitis (AIH, and chronic hepatitis B (CHB.Sera from 84 patients with Autoimmune Hepatitis (AIH type 1 and 88 patients with Chronic Hepatitis B (CHB were tested for Immunoglobulin A and G antibodies to Gliadin, Immunoglobulin A antibodies to tissue transglutaminase using enzyme immunoassay, and Immunoglobulin A anti-endomysial antibodies by both indirect immunofluorescence, and enzyme immunoassay. The patients positive for anti-endomysial antibodies and/or anti tissue transglutaminase antibodies were considered for deuodenal biopsy. The study was approved by Research Center for Gastroenterology and Liver Disease Ethics Committee and all patients gave their written informed consent to participate.Immunoglobulin A anti-endomysial and Immunoglobulin A anti-gliadin antibodies were positive in two out of 84 patients with AIH. Moreover, Immunoglobulin A anti-gliadin antibodies were positive in another patient who was also positive for anti tissue transglutaminase antibodies. Tissue transglutaminase antibodies were positive in eight (9.1% of 88 patients with CHB, two of which were also positive for anti-endomysial antibodies. One of the patients with CHB was only positive for anti-endomysial antibodies.Compared with the general population, the prevalence of celiac autoantibodies in CHB and AIH patients is relatively high, and it is noteworthy that most positive patients were asymptomatic for celiac disease. We suggest screening for celiac disease before and during treatment in patients with viral and autoimmune hepatitis.

  16. 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.

  17. Thyroid autoantibodies post moderate doses of iodized oil in adolescence

    International Nuclear Information System (INIS)

    In this study we examined the effect of a single moderate doses of iodized oil(400 mg) on the production of thyroid autoantibodies, namely thyroid peroxidase(TPO), thyroglobulin(TG), and TSH - receptor(TRAB) antibodies.This is compared with daily dose of 100 mg of L-thyroxine for 6 months.A group of 87 adolescent school girls were selected from a moderately iodine deficient area, on the basis of having goitre grade Ib and above(WHO classification).Randomly the girls were divided into two groups: Group 1 received L-thyroxine (n =46).Group 2 received oral iodized oil (n =41).The prevalence of TPO Ab in the whole group before treatment was 3.4%.No significant level of TRAB was detected in any of the girls before or after treatment. All the patients who had TPO Ab or TG Ab at the start of the study were found to be in group 1, this happened by chance because all the samples were not tested until the end of the study.No patient in group 2 found to have any of the antibodies.By the end of the 14 months follow up period one patient from group 1, who had no TPO Ab or TG Ab, developed TG Ab, while 5 patients from group 2 developed either or both antibodies.The difference between the 2 groups was found not significant (P< 0.1). These findings suggest that introducing moderate dose of iodized oil early in life might have no major ill effect on thyroid immunology as reflected by the production of the main 3 autoantibodies. (Author)

  18. A pseudobiospecific hollow fiber cartridge for in vitro adsorption of autoantibodies from pathological serum

    Directory of Open Access Journals (Sweden)

    Ventura R.C.A.

    2000-01-01

    Full Text Available The affinity filtration technique using histidine as a pseudobiospecific ligand immobilized on poly(ethylene vinyl alcohol hollow fiber membranes (His-PEVA was used to remove autoantibodies from serum of patients with autoimmune disease. The effects of buffering solution conditions on the efficiency of autoantibodies removal was studied. The removal of anti-dsDNA, anti-SS-A/Ro, anti-Sm, anti-Sm/RNP and anti-cardiolipin autoantibodies present in the serum was investigated, comparing the efficiency between Hepes and Tris-HCl buffers. The results showed the potential of the membrane to remove all the autoantibodies studied. Anti SS-A/Ro was removed more efficiently in Tris-HCl buffer system rather than with the Hepes buffer.

  19. Simultaneous occurrence of fetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    DEFF Research Database (Denmark)

    Taaning, Ellen; 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...

  20. Anticardiolipin autoantibodies in serum samples and cryoglobulins of patients with chronic hepatitis C infection

    OpenAIRE

    Sthoeger, Z; Fogel, M.; Smirov, A.; Ergas, D; Lurie, Y; Bass, D.; Geltner, D.; Malnick, S.

    2000-01-01

    OBJECTIVE—Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition, a variety of autoantibodies are found in patients with HCV. The prevalence, nature, and clinical significance of anticardiolipin (aCL) autoantibodies in serum samples of patients with HCV were therefore investigated.
PATIENTS AND METHODS—A prospective study of 48 consecutive patients with chronic HCV with no evidence of previous hepatitis B virus (HBV) infection or any other autoimmune...

  1. Antenatal and postnatal combined therapy for autoantibody-related congenital atrioventricular block

    OpenAIRE

    Di Mauro, Antonio; Caroli Casavola, Vita; Favia Guarnieri, Giovanna; Calderoni, Grazia; Cicinelli, Ettore; Laforgia, Nicola

    2013-01-01

    Background Autoantibody-related congenital heart block (CHB) is an autoimmune condition in which trans placental passage of maternal autoantibodies cause damage to the developing heart conduction system of the foetus. Case presentation We report a case of an Italian 31–year-old woman, in a good clinical status, referred to our Centre at 26 weeks of her first pregnancy, because of foetal bradycardia, found during routine foetal ultrasonography. Foetal echocardiography revealed a 3rd degree CHB...

  2. A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin

    OpenAIRE

    Gude, Neil M.; Stevenson, Janet L.; Sheehan, Penelope M.; Brennecke, Shaun P.

    2013-01-01

    Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic reticulum chaperone protein calreticulin has been reported in various autoimmune and parasitic diseases. It has been reported that adenomyosis is associated with the presence of autoantibodies, in particular to phospholipids; however, it is not known whether it is associated with autoimmunity to calreticulin. Results. A 35-year-old gravida 4 para 4 woman presented with a history of many years of intractable meno...

  3. Autoantibody-mediated angiotensin receptor activation contributes to preeclampsia through TNF-alpha signaling

    OpenAIRE

    Irani, Roxanna A.; Zhang, Yujin; Zhou, Cissy Chenyi; Blackwell, Sean C.; Hicks, M. John; Ramin, Susan M.; Kellems, Rodney E.; Xia, Yang

    2010-01-01

    Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy whose pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin II type I receptor agonistic autoantibody (AT1-AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor alpha (TNF-α) is also associated with the disease, however it is unknown if this factor directly contributes to preeclamptic symptoms. Here we report ...

  4. Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid

    OpenAIRE

    Marignier, R.; Ruiz, A.; Cavagna, S.; Nicole, A; Watrin, C.; Touret, M.; Parrot, S; Malleret, G.; Peyron, C.; Benetollo, C.; Auvergnon, N.; Vukusic, S.; Giraudon, P.

    2016-01-01

    Background Devic’s neuromyelitis optica (NMO) is an autoimmune astrocytopathy, associated with central nervous system inflammation, demyelination, and neuronal injury. Several studies confirmed that autoantibodies directed against aquaporin-4 (AQP4-IgG) are relevant in the pathogenesis of NMO, mainly through complement-dependent toxicity leading to astrocyte death. However, the effect of the autoantibody per se and the exact role of intrathecal AQP4-IgG are still controversial. Methods To exp...

  5. Autoantibodies and hepatitis C virus genotypes in chronic hepatitis C patients in Estonia

    Institute of Scientific and Technical Information of China (English)

    Eva Zusinaite; Kaja Metsküla; Riina Salupere

    2005-01-01

    AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes.METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA),anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region.RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%),TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases,sera were positive for two autoantibodies (ANA and SMA).AMA, PCA and LKMA1 were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%)patients.CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1: 10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.

  6. Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome.

    Directory of Open Access Journals (Sweden)

    Vito Lampasona

    Full Text Available Autoantibodies to enterocyte antigens harmonin (75 kDa USH1C protein and villin (actin-binding 95 kDa protein are associated with the Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome. In this study we evaluated the diagnostic value of harmonin and villin autoantibodies in IPEX and IPEX-like syndromes. Harmonin and villin autoantibodies were measured by a novel Luminescent-Immuno-Precipitation-System (LIPS quantitative assay, in patients with IPEX, IPEX-like syndrome, Primary Immunodeficiencies (PID with enteropathy, all diagnosed by sequencing of the FOXP3 gene, and in type 1 diabetes (T1D, celiac disease and healthy blood donors as control groups. Harmonin and villin autoantibodies were detected in 12 (92% and 6 (46% of 13 IPEX patients, and in none of the IPEX-like, PID, T1D, celiac patients, respectively. All IPEX patients, including one case with late and atypical clinical presentation, had either harmonin and/or villin autoantibodies and tested positive for enterocyte antibodies by indirect immunofluorescence. When measured in IPEX patients in remission after immunosuppressive therapy or hematopoietic stem cell transplantation, harmonin and villin autoantibodies became undetectable or persisted at low titers in all cases but one in whom harmonin autoantibodies remained constantly high. In one patient, a peak of harmonin antibodies paralleled a relapse phase of enteropathy. Our study demonstrates that harmonin and villin autoantibodies, measured by LIPS, are sensitive and specific markers of IPEX, differentiate IPEX, including atypical cases, from other early childhood disorders associated with enteropathy, and are useful for screening and clinical monitoring of affected children.

  7. Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System

    OpenAIRE

    Marleen eVan Coevorden-Hameete; Maarten eTitulaer; Marco eSchreurs; Esther ede Graaff; Peter eSillevis Smitt; Casper eHoogenraad

    2016-01-01

    Autoimmune encephalitis (AIE) is a group of disorders in which autoantibodies directed at antigens located on the plasma membrane of neurons induce severe neurological symptoms. In contrast to classical paraneoplastic disorders, AIE patients respond well to immunotherapy. The detection of neuronal surface autoantibodies in patients’ serum or CSF therefore has serious consequences for the patients’ treatment and follow-up and requires the availability of sensitive and specific diagnostic tests...

  8. Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

    OpenAIRE

    Piccoli, Luca; Campo, Ilaria; Fregni, Chiara Silacci; Rodriguez, Blanca Maria Fernandez; Minola, Andrea; Sallusto, Federica; Luisetti, Maurizio; Corti, Davide; Lanzavecchia, Antonio

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in ...

  9. Experimental Autoimmune Vasculitis : An Animal Model of Anti-neutrophil Cytoplasmic Autoantibody-Associated Systemic Vasculitis

    OpenAIRE

    Little, Mark A.; Smyth, Lucy; Salama, Alan D; Mukherjee, Sriparna; Smith, Jennifer; Haskard, Dorian; Nourshargh, Sussan; Cook, H. Terence; Charles D. Pusey

    2009-01-01

    The morbidity burden associated with anti-neutrophil cytoplasmic autoantibody-associated vasculitis is increasing, and many novel biological therapies are now entering the drug development pipeline. There is thus an urgent need to develop a representative animal model to facilitate testing of these agents. We previously examined the effect of antineutrophil cytoplasmic autoantibody on leukocyte-endothelial interactions in WKY rats via immunization with human myeloperoxidase. We now seek to ex...

  10. Are Pancreatic Autoantibodies Associated with Azathioprine-Induced Pancreatitis in Crohns Disease?

    OpenAIRE

    Weersma, Rinse K; Manou R Batstra; 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 autoantibody positive Crohn’s disease patients might have a low grade inflammation of the pancreas which may be aggravated by the introduction of azathioprine, resulting in clinically overt acute pancr...

  11. Transverse Myelitis Associated with Anti-Ro (SSA) Autoantibodies: A Record of Two Cases

    OpenAIRE

    Melikyan, G.; Abdelrahman, M. H.; A. D’Suoza; Akhtar, N; Elzouki, A. N.; Hammoudeh, M.

    2012-01-01

    Transverse myelitis (TM) is an inflammatory process involving a restricted area of the spinal cord. The usual dramatic presentation makes TM a medical emergency. Early detection and aggressive therapy are required in order to improve the prognosis. The association of this unique clinical phenotype and autoantibody provides circumstantial evidence that an autoimmune aetiology might be involved. We describe two cases of TM associated with anti-Ro (SSA) autoantibodies without connective tissue d...

  12. Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

    OpenAIRE

    Chon, Suk; Choi, Moon Chan; Lee, Yun Jung; Hwang, You Cheol; Jeong, In-Kyung; Oh, Seungjoon; Ahn, Kyu Jeung; Chung, Ho Yeon; Woo, Jeong-taek; Kim, Sung-Woon; Kim, Jin-Woo; Kim, Young Seol

    2011-01-01

    Background Type 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. Methods To evaluate the mechanism of hypoglycemia, we measured th...

  13. A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin.

    Science.gov (United States)

    Gude, Neil M; Stevenson, Janet L; Sheehan, Penelope M; Brennecke, Shaun P

    2013-01-01

    Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic reticulum chaperone protein calreticulin has been reported in various autoimmune and parasitic diseases. It has been reported that adenomyosis is associated with the presence of autoantibodies, in particular to phospholipids; however, it is not known whether it is associated with autoimmunity to calreticulin. Results. A 35-year-old gravida 4 para 4 woman presented with a history of many years of intractable menorrhagia. Histopathological examination of a subsequent hysterectomy specimen revealed a bulky uterus, a poorly developed secretory endometrium with decidualization of the stroma and chronic endometritis, as well as the presence of adenomyosis uteri. IgG autoantibodies to calreticulin were measured in the plasma of this and 234 other patients. Nine (3.8%) patients tested positive. The titer of anticalreticulin IgG autoantibody in the sole case with adenomyosis was approximately 8 times the average of other positive-testing samples. Conclusions. The etiology of adenomyosis is unclear. The presence of a high titer, blocking anticalreticulin autoantibody may directly increase the risk that adenomyosis might develop. It is also possible that the expansion of endometrial glandular tissue, as well as elevated estrogens, during adenomyosis may lead to elevated calreticulin, which induces an autoimmune reaction to it. Further study is required to determine whether there is a significant association between adenomyosis and the prevalence of calreticulin autoantibodies. PMID:26425587

  14. A Novel Method for Detecting p53 Autoantibodies in Sera of Patients with NSCLC

    Directory of Open Access Journals (Sweden)

    Kai TANG

    2009-09-01

    Full Text Available Background and objective Serum autoantibody detection is useful means for the early diagnosis and prognosis of cancer. So our objective was to synthesize peptide array to analyse p53 autoantibodies in the sera of patients with non small cell lung cancer (NSCLC. Methods Cellulose-bound overlapping peptides (12 mers derived from p53 wild type protein were synthesized using SOPTs synthesis technique by an AutoSpot robot –ASP SL (Intavis, Germany. The membrane was incubated with 1/400 dilutions of p53 monoclonal antibody (Sc-53394 to establish a new approach to detect p53 antibody, and the epitopes of the p53 monoclonal antibody is already known. We analysed the p53 autoantibodies from the sera of NSCLC and controls by peptide array and ELISA. Results We synthesized on cellulose membranes twelve-amino-acid overlapping peptides which included all of the sequences of the polypeptide chain of p53. The p53 autoantibody was positive in seven cases of thirty patients’ sera with NSCLC and was negative in sera of the controls, with the same result of ELISA. Conclusion The peptide array could be applied not only to detect the autoantibodies in the sera of patients with lung cancer, but also to map the epitopes of the autoantibodies which might be useful for the early diagnosis and prognosis of cancer.

  15. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients

    OpenAIRE

    Cho, Michael Jeffrey; Lo, Agnes S.Y.; Mao, Xuming; Nagler, Arielle R.; Christoph T Ellebrecht; 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

    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 ant...

  16. 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

  17. 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

    autoimmune gastritis, transglutaminase (TGA) in celiac disease, and 21-hydroxylase (21-OHA) in autoimmune hypoadrenalism. In addition to the MHC region, we identify SNPs in five susceptibility loci (IFIH1, PTPN22, SH2B3, BACH2, and CTLA4) as significantly associated with more than one autoantibody at a false...

  18. Evidence for intranasal anti-nuclear autoantibodies in Chronic Rhinosinusitis with Nasal Polyps.

    Science.gov (United States)

    Tan, Bruce K.; Li, Quan-Zhen; Suh, Lydia; Kato, Atsushi; Conley, David B.; Chandra, Rakesh K.; Zhou, Jinchun; Norton, James; Carter, Roderick; Hinchcliff, Monique; Harris, Kathleen; Peters, Anju; Grammer, Leslie C.; Kern, Robert C.; Mohan, Chandra; Schleimer, Robert P.

    2011-01-01

    BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition of the nasal passage and paranasal sinuses characterized by Th2 biased inflammation with elevated levels of BAFF, B-lymphocytes, and immunoglobulins. Since high levels of BAFF are associated with autoimmune diseases, we assessed for evidence of autoimmunity in patients with CRS. OBJECTIVES The objective of this study was to investigate for the presence of autoantibodies in sinonasal tissue from patients with CRS. METHODS Standardized nasal tissue specimens were collected from patients with CRS and control subjects and assayed for immunoglobulin production, autoantibody levels, tissue distribution of immunoglobulins and binding potential of antibodies in nasal tissue using a multiplexed autoantibody microarray, ELISA and immunofluoresence. RESULTS Elevated levels of several specific autoantibodies were found in nasal polyp tissue in comparison with control tissue and inflamed tissue from non-polypoid CRS (CRSsNP) (p<0.05). In particular, nuclear-targeted autoantibodies such as anti-dsDNA IgG and IgA antibodies were found at elevated levels in nasal polyps (p<0.05) and particularly in nasal polyps from patients requiring revision surgery for recurrence. Direct immunofluorescence staining demonstrated diffuse epithelial and sub-epithelial deposition of IgG and increased numbers of IgA secreting plasma cells not seen in control nasal tissue. CONCLUSIONS Autoantibodies, particularly those against nuclear antigens, are present at locally elevated levels in nasal polyps. The presence of autoantibodies suggests that the microenvironment of a nasal polyp promotes the expansion of self-reactive B-cell clones. While the pathogenicity of these antibodies remains to be elucidated, the presence of elevated anti-dsDNA antibodies is associated with a clinically more aggressive form of CRSwNP requiring repeated surgery. PMID:21996343

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    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.

  1. Female mouse fetal loss mediated by maternal autoantibody.

    Science.gov (United States)

    Wang, Li; Zhou, Dun; Lee, Ji; Niu, Haitao; Faust, Thomas W; Frattini, Stephen; Kowal, Czeslawa; Huerta, Patricio T; Volpe, Bruce T; Diamond, Betty

    2012-06-01

    Systemic lupus erythematosus (SLE), a disease of women during childbearing years, is characterized by the production of double-stranded DNA antibodies. A subset of these antibodies, present in 40% of patients, cross-reacts with the NR2A and NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR). In this study, we show that, in mouse models, these antibodies cause a loss of female fetus viability by inducing apoptosis of NR2A-expressing neurons within the brainstem late in fetal development; gender specificity derives from a time-dependent increased expression of NR2A in female brainstem or increased vulnerability of female fetal neurons to signaling through NR2A-containing NMDARs. This paradigm is consistent with available data on the sex ratio of live births of women with SLE. It represents a novel mechanism by which maternal autoantibodies can severely affect fetal health in a gender-specific fashion and raises the question of how many maternal antibodies affect brain development or exhibit gender-specific fetal effects. PMID:22565825

  2. Autoantibody to the gastrin receptor in pernicious anemia

    International Nuclear Information System (INIS)

    The authors examined serum IgG fractions from 20 patients with pernicious anemia and 25 control subjects for their capacity to inhibit binding of [125I]15-leu human gastrin-17 to parietal-cell-enriched gastric mucosal cells. IgG fractions from six patients reduced gastrin binding by 45.6 +/- 12.2 per cent, as compared with a reduction of 1.8 +/- 0.7 per cent by fractions from the 25 controls. The fractions from these six patients also reduced gastrin-stimulated [14C]aminopyrine uptake by gastric cells (an index of gastric acid secretory activity in vitro) by 50.2 +/- 8.4 per cent (mean +/- S.D.), as compared with 9.2 +/- 4.1 per cent for the controls. IgG fractions from six other patients that did not reduce gastrin binding also inhibited gastrin-stimulated [14C]aminopyrine uptake, by 48.1 +/- 9.1 per cent. These reductions in gastrin binding and aminopyrine uptake were abolished by absorption of the IgG fractions with suspensions of viable gastric mucosal cells but not by absorption with liver or kidney cells. The IgG fractions did not inhibit [3H]histamine binding or histamine-stimulated [14C]aminopyrine uptake. These results suggest that serum IgG from some patients with pernicious anemia contains autoantibodies to the gastrin receptor

  3. Autoantibodies and immunoglobulins among atomic-bomb survivors

    International Nuclear Information System (INIS)

    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)

  4. Novel monoclonal autoantibody specificity associated with ribonucleoprotein complexes

    International Nuclear Information System (INIS)

    The authors describe an IgG/sub 2a/, kappa monoclonal autoantibody (mAb) F78 derived from a 6-month old MRL-Mp lpr/lpr mouse that recognizes a novel epitope associated with small nuclear ribonuclear protein complexes (snRNP). Indirect immunofluorescent staining of HEp-2 cells with F78 showed a nonnucleolar speckled nuclear pattern characteristic of anti-RNP and anti-Sm mAbs which could be abrogated by pretreating fixed cells with 0.1M HCl prior to staining. Immunoblots of whole cell extracts (dissociated in SDS, urea and mercaptan at 40C then subjected to SDS-PAGE) showed that F78 selectively bound to a component of M/sub r/ = 100,000 clearly distinct from components recognized by two mAbs described by Billings et al that detected, respectively, proteins of M/sub r/ = 70,000 associated with RNP and M/sub r/ = 13,000 associated with Sm. Incubation of extracts at 1000C prior to SDS-PAGE eliminated subsequent binding of F78 but not of the other nAbs. F78 as well as the other mAbs selectively immunoprecipitated characteristic patterns of small nuclear RNAs (U1, U2, U4, U5, U6) from extracts of 32P-phosphate labeled HeLa cells. These results suggest a new specificity associated with snRNP that is recognized in the MRL autoimmune response

  5. P53 autoantibodies in 1006 patients followed up for breast cancer

    International Nuclear Information System (INIS)

    Serial plasma samples from 1006 patients with breast cancer revealed: (i) no correlation of p53 autoantibody status with disease status at the time of sample collection, or with menopausal status at time of primary diagnosis of breast cancer; (ii) 155 out of 1006 (15%) of patients were positive for p53 autoantibodies, and these patients tended to have a persistent autoantibody status throughout follow up, irrespective of disease behaviour; and (iii) where a negative autoantibody status was found at primary diagnosis of breast cancer, this negative status persisted throughout follow up, irrespective of later disease behaviour. We conclude that screening for p53 autoantibody status is not informative on residual tumour activity nor on therapeutic responsiveness. Dysfunction of the tumour-suppressor protein, p53, may be due to either mutational or epigenetic factors, each of which may lead to accumulation of cytoplasmic p53. Abnormal accumulation of p53 in breast cancer tissue is predictive of poor prognosis [1,2]. Humoral studies [3,4] have shown that cancer patients may develop immunity to abnormally expressed p53, as revealed by p53 autoantibodies in the blood. Again, prognostic correlates have been noted, with presence of circulating p53 autoantibodies at diagnosis of breast cancer being associated with reduced overall survival [5,6] and with poor prognostic factors such as high histological grade and the absence of hormone receptors [5,7,8]. Little is known of the potential value of p53 autoantibody in follow up of cancer. In lung cancer there is evidence that autoantibodies to p53 may provide a useful tool to monitor response to therapy [9,10], whereas serial measurements of autoantibodies to p53 in 40 patients with advanced ovarian cancer were not found to be clinically useful [11]. In breast cancer some 30% of node-negative patients will relapse within 5 years, but there is no current means to predict those who are at risk. We performed the present study to

  6. Infection-induced autoantibodies and pregnancy related pathology: an animal model.

    Science.gov (United States)

    Petrušić, Vladimir; Živković, Irena; Muhandes, Lina; Dimitrijević, Rajna; Stojanović, Marijana; Dimitrijević, Ljiljana

    2014-01-01

    In addition to being the main cause of mortality worldwide, bacterial and viral infections can be the cause of autoimmune and pregnancy disorders as well. The production of autoantibodies during infection can be explained by various mechanisms, including molecular mimicry, bystander cell activation and epitope spreading. Conversely, bacterial and viral infections during pregnancy are especially dangerous for the fetus. It is documented that infection-induced inflammatory processes mediated by Toll-like receptors (TLR) represent the main cause of preterm labour. We used two crucial bacterial components and TLR ligands, namely peptidoglycan and lipopolysaccharide, to stimulate BALB/c mice before immunisation with tetanus toxoid. Tetanus toxoid is an inactive form of the toxin produced by bacterium Clostridium tetani and shares structural similarity with plasma protein β2-glycoprotein I. Treatment with peptidoglycan and lipopolysaccharide in combination with tetanus toxoid induced the production of pathological autoantibodies, different fluctuations in natural autoantibodies and different types of reproductive pathology in treated animals, with peptidoglycan treatment being more deleterious. We propose that the production of pathological autoantibodies, TLR activation and changes in natural autoantibodies play crucial roles in infection-induced reproductive pathology in our animal model. PMID:23657219

  7. Association of susceptible genetic markers and autoantibodies in rheumatoid arthritis

    Indian Academy of Sciences (India)

    Vasanth Konda Mohan; Nalini Ganesan; Rajasekhar Gopalakrishnan

    2014-08-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown aetiology resulting in inflammation of the synovium, cartilage and bone. The disease has a heterogeneous character, consisting of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital role in susceptibility to RA as the heritability of RA is between 50 and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Non-HLA genes, i.e. tumour necrosis factor- (TNF-) within the MHC (major histocompatibility complex) have also been investigated for association with RA. Although, some contradictory results have originated from several studies on TNF- gene, the data published so far indicate the possible existence of TNF- gene promoter variants that act as markers for disease severity and response to treatment in RA. The correlation of HLA and non-HLA genes within MHC region is apparently interpreted. A considerable number of confirmed associations with RA and other autoimmune disease susceptibility loci including peptidylarginine deiminase type 4 (PADI4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), signal transducer and activator of transcription (STAT4), cluster of differentiation 244 (CD244) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), located outside the MHC have been reported recently. In this review, we aim to give an update on recent progress in RA genetics, the importance of the combination of HLA-DRB1 alleles, non-HLA gene polymorphism, its detection and autoantibodies as susceptibility markers for early RA disease.

  8. [Autoantibodies to glutamate receptors in children with chronic posttraumatic headache].

    Science.gov (United States)

    Goriunova, A V; Bazarnaia, N A; Sorokina, E G; Semenova, N Iu; Globa, O V; Semenova, Zh B; Pinelis, V G; Roshal', L M; Maslova, O I

    2006-01-01

    Autoantibodies (aAB) to AMPA (Glu R1 subunit) and NMDA (NR 2A subunit) glutamate receptors were studied in blood serum of 60 children, aged 7-16 years, with chronic posttraumatic headache after mild skull injury. All the children were divided into 2 groups: group 1 included 48 children with concussion of the brain, group 2--12 children with brain contusion. Group 1 was divided into 2 subgroups: subgroup 1a comprised 34 children with single concussion and subgroup 1b--14 children with repeated concussion. The aAB level was determined 6 months and 1 year after skull injury. The aAB concentration was expressed in percents to the control level being considered significant if the increase was higher than 120%. The increased NMDA aAB level was observed during the first year after skull injury. In the la subgroup, the NR2 aAB level in blood serum was 145 +/- 12,6%, in the 1b one--108 +/- 12,4%, in group 2--165 +/- 34%. The content of aAB to AMPA receptors was elevated only in children of lb subgroup and group 2 (150 +/- 16,8% and 167 +/- 31,3%, respectively). The EEG examination of this group revealed the nonspecific paroxysmal discharges in 18% of cases and epileptiform activity in 6% of children. The results obtained suggest that children with posttraumatic headache have elevated levels of aAB to glutamate receptors, hyperstimulation of which reflects hypoxic processes in the brain, and are in need of metabolic therapy. PMID:16972597

  9. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    Science.gov (United States)

    Negm, Ola H; Hamed, Mohamed R; Schoen, Robert E; Whelan, Richard L; Steele, Robert J; Scholefield, John; Dilnot, Elizabeth M; Shantha Kumara, H M C; Robertson, John F R; Sewell, Herbert F

    2016-01-01

    Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice. PMID:27383396

  10. 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.

  11. A novel autoantibody in patients with primary hypertension:antibody against L-type Ca2+ channel

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zi-hua; WANG Jun; XIAO Hua; CHEN Zhi-jian; WANG Min; CHENG Xiang; LIAO Yu-hua

    2008-01-01

    Background Recently,it has been proposed that the autoantibodies against various cardiovascular receptors play a role in the pathogenesis of primary hypertension.In this study,we aimed to identify whether or not there are autoantibodies against cardiovascular L-type Ca2+ channels in patients with primary hypertension.Methods A peptide corresponding to the sequence 2-16 of the alc-subunit of L-type Ca2+ channel was used as an antigen to screen the autoantibodies from 90 patients with primary hypertension and 45 healthy controls by an enzyme-linked immunosorbent assay(ELISA).The clinical data of 90 hypertensive patients were compared between patients with and without these autoantibodies.Results Serum from 3(6.7%)of the 45 healthy controls,33(36.7%)of 90 hypertensives showed positive responses in ELISA(P<0.01).The prevalence of such autoantibodies in two subgroups of hypertensives with coronary heart disease(9/21,57.1 4%,P<0.05)and left ventricular diastolic dysfunction(28/63,44.4%,P<0.05)was higher than in those without the corresponding complications.And the patients with such autoantibodies had lower E/A than patients without such autoantibodies(O.803±0.191 vs 1.004=L+0.322,P=0.002).Conclusion There are autoantibodies against vascular L-type Ca2+ channels in patients with primary hypertension.

  12. AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies.

    Science.gov (United States)

    Meyer, Steffen; Woodward, Martin; Hertel, Christina; Vlaicu, Philip; Haque, Yasmin; Kärner, Jaanika; Macagno, Annalisa; Onuoha, Shimobi C; Fishman, Dmytro; Peterson, Hedi; Metsküla, Kaja; Uibo, Raivo; Jäntti, Kirsi; Hokynar, Kati; Wolff, Anette S B; Krohn, Kai; Ranki, Annamari; Peterson, Pärt; Kisand, Kai; Hayday, Adrian

    2016-07-28

    APS1/APECED patients are defined by defects in the autoimmune regulator (AIRE) that mediates central T cell tolerance to many self-antigens. AIRE deficiency also affects B cell tolerance, but this is incompletely understood. Here we show that most APS1/APECED patients displayed B cell autoreactivity toward unique sets of approximately 100 self-proteins. Thereby, autoantibodies from 81 patients collectively detected many thousands of human proteins. The loss of B cell tolerance seemingly occurred during antibody affinity maturation, an obligatorily T cell-dependent step. Consistent with this, many APS1/APECED patients harbored extremely high-affinity, neutralizing autoantibodies, particularly against specific cytokines. Such antibodies were biologically active in vitro and in vivo, and those neutralizing type I interferons (IFNs) showed a striking inverse correlation with type I diabetes, not shown by other anti-cytokine antibodies. Thus, naturally occurring human autoantibodies may actively limit disease and be of therapeutic utility. PMID:27426947

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

    International Nuclear Information System (INIS)

    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.)

  14. Anti-rods/rings autoantibody generation in hepatitis C patients during interferon-α/ribavirin therapy.

    Science.gov (United States)

    Keppeke, Gerson Dierley; Calise, S John; Chan, Edward K L; Andrade, Luis Eduardo C

    2016-02-14

    Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α (IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies (ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings (RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings (anti-RR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon. PMID:26877604

  15. Basophil phenotypes in chronic idiopathic urticaria in relation to disease activity and autoantibodies.

    Science.gov (United States)

    Eckman, John A; Hamilton, Robert G; Gober, Laura M; Sterba, Patricia M; Saini, Sarbjit S

    2008-08-01

    Potentially pathogenic IgG autoantibodies to IgE or its receptor, Fc epsilonRIalpha, have been detected in approximately 40% of chronic idiopathic urticaria (CIU) patients. CIU patients' basophils display distinct altered Fc epsilonRIalpha-mediated degranulation. CIU patients with basophil histamine release in response to polyclonal goat anti-human IgE > or = 10% are classified as CIU responders (CIU-R) and CIU non-responders (CIU-NR). We compared the presence of autoantibodies to basophil degranulation phenotypes and to disease status (active or inactive). Sera were collected from non-CIU subjects and CIU subjects who participated in a longitudinal study of disease severity and had defined basophil degranulation phenotypes. Immunoenzymetric assays (IEMA) quantified IgG anti-Fc epsilonRIalpha and anti-IgE. IgG anti-Fc epsilonRIalpha antibody was detected in 57% of CIU-R (n=35), 55% of CIU-NR (n=29), and 57% of non-CIU subjects (n=23), whereas IgG anti-IgE was present in 43% of CIU-R, 45% of CIU-NR, and 30% of non-CIU subjects. Both the autoantibody levels and the functional basophil phenotype remained stable in subjects with active disease (n=16), whereas there was an enhancement in basophil function as subjects evolved into a state of remission (n=6), which appears independent of the presence of autoantibody. IEMAs detected a similar frequency of autoantibodies in CIU-R, CIU-NR, and non-CIU subjects. Basophil function may be independent of IEMA-detected autoantibodies. PMID:18356810

  16. Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita.

    Science.gov (United States)

    Ellebrecht, Christoph T; Srinivas, Girish; Bieber, Katja; Banczyk, David; Kalies, Kathrin; Künzel, Sven; Hammers, Christoph M; Baines, John F; Zillikens, Detlef; Ludwig, Ralf J; Westermann, Jürgen

    2016-04-01

    Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7). Immunization of SJL/J mice with recombinant murine COL7 results in break of tolerance and skin blisters. Strikingly, despite circulating autoantibodies, the same genetic background and identical environmental conditions, 20% of mice remain healthy. To elucidate the regulation of the transition from the presence of autoantibodies to overt autoimmune disease, we characterized the innate and adaptive immune response of mice that remain healthy after immunization and compared it to mice that developed skin disease. Both clinically healthy and diseased SJL/J mice showed circulating autoantibodies and deposition of complement-fixing IgG2c autoantibodies and C3 at the dermal-epidermal junction. However, only in diseased animals significant neutrophil infiltration and increase in FcgRIV expression were observed in the skin. In contrast, the expression of T cell signature cytokines in the T cell zone of the draining lymph node was comparable between clinically healthy and diseased animals after immunization. Surprisingly, health was associated with a decreased expression of CD11c, TNFA and KC (CXCL1) in the skin prior to immunization and could be predicted with a negative predictive value of >80%. Furthermore, mice that did not develop clinical disease showed a significantly higher richness and distinctly clustered diversity of their skin microbiota before immunization. Our data indicate that the decision whether blisters develop in the presence of autoantibodies is governed in the skin rather than in the lymph node, and that a greater richness of cutaneous bacterial species appears to be protective. PMID:26341384

  17. 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.

  18. Lupus anti-ribosomal P autoantibody proteomes express convergent biclonal signatures.

    Science.gov (United States)

    Al Kindi, M A; Colella, A D; Beroukas, D; Chataway, T K; Gordon, T P

    2016-04-01

    Lupus-specific anti-ribosomal P (anti-Rib-P) autoantibodies have been implicated in the pathogenesis of neurological complications in systemic lupus erythematosus (SLE). The aim of the present study was to determine variable (V)-region signatures of secreted autoantibody proteomes specific for the Rib-P heterocomplex and investigate the molecular basis of the reported cross-reactivity with Sm autoantigen. Anti-Rib-P immunoglobulins (IgGs) were purified from six anti-Rib-P-positive sera by elution from enzyme-linked immunosorbent assay (ELISA) plates coated with either native Rib-P proteins or an 11-amino acid peptide (11-C peptide) representing the conserved COOH-terminal P epitope. Rib-P- and 11-C peptide-specific IgGs were analysed for heavy (H) and light (L) chain clonality and V-region expression using an electrophoretic and de-novo and database-driven mass spectrometric sequencing workflow. Purified anti-Rib-P and anti-SmD IgGs were tested for cross-reactivity on ELISA and their proteome data sets analysed for shared clonotypes. Anti-Rib-P autoantibody proteomes were IgG1 kappa-restricted and comprised two public clonotypes defined by unique H/L chain pairings. The major clonotypic population was specific for the common COOH-terminal epitope, while the second shared the same pairing signature as a recently reported anti-SmD clonotype, accounting for two-way immunoassay cross-reactivity between these lupus autoantibodies. Sequence convergence of anti-Rib-P proteomes suggests common molecular pathways of autoantibody production and identifies stereotyped clonal populations that are thought to play a pathogenic role in neuropsychiatric lupus. Shared clonotypic structures for anti-Rib-P and anti-Sm responses suggest a common B cell clonal origin for subsets of these lupus-specific autoantibodies. PMID:26646815

  19. 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.

  20. Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA)

    DEFF Research Database (Denmark)

    Brimnes, J; Halberg, P; Jacobsen, Søren;

    1997-01-01

    The objective of this study was to characterize antigens recognized by neutrophil-specific autoantibodies from patients with RA. Sera from 62 RA patients were screened by indirect immunofluorescence (IIF). Positive sera were further tested by ELISAs for antibodies against various granule proteins...... with bands of 25-35 kD from nuclei. In conclusion, anti-neutrophil autoantibodies from RA patients recognize different antigens in the cytoplasm and in the nucleus. Lactoferrin is one of the common antigens recognized, but also unknown nuclear antigens of 25-35 kD mol. wt are involved....

  1. Prevalence of serum N-methyl-D-aspartate receptor autoantibodies in refractory psychosis

    OpenAIRE

    Beck*, Katherine Emma; Lally, John Alexander; Shergill, Sukhwinder S.; Bloomfield, Michael A.P.; MacCabe, James Hunter; Gaughran, Fiona Patricia; Howes, Oliver

    2015-01-01

    N-methyl-d-aspartate receptor (NMDA-R) autoantibodies have been reported in people with acute psychosis. We hypothesised that their presence may be implicated in the aetiology of treatment-refractory psychosis. We sought to ascertain the point prevalence of NMDA-R antibody positivity in patients referred to services for treatment-refractory psychosis. We found that 3 (7.0%) of 43 individuals had low positive NMDA-R antibody titres. This suggests that NMDA-R autoantibodies are unlikely to acco...

  2. Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.

    Directory of Open Access Journals (Sweden)

    Sharon A Chung

    2011-03-01

    Full Text Available Systemic lupus erythematosus (SLE is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811 and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906 SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20 compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04, with p(heterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti-dsDNA + SLE and were not associated with anti-dsDNA - SLE. In conclusion, we identified differential genetic associations with SLE based on anti-dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti-dsDNA - SLE.

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

    Directory of Open Access Journals (Sweden)

    N. V. Piven

    2014-07-01

    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

  4. From autoantibody research to standardized diagnostic assays in the management of human diseases - report of the 12th Dresden Symposium on Autoantibodies.

    Science.gov (United States)

    Conrad, K; Andrade, L E C; Chan, E K L; Mahler, M; Meroni, P L; Pruijn, G J M; Steiner, G; Shoenfeld, Y

    2016-07-01

    Testing for autoantibodies (AABs) is becoming more and more relevant, not only for diagnosing autoimmune diseases (AIDs) but also for the differentiation of defined AID subtypes with different clinical manifestations, course and prognosis as well as the very early diagnosis for adequate management in the context of personalized medicine. A major challenge to improve diagnostic accuracy is to harmonize or even standardize AAB analyses. This review presents the results of the 12th Dresden Symposium on Autoantibodies that focused on several aspects of improving autoimmune diagnostics. Topics that are addressed include the International Consensus on ANA Patterns (ICAP) and the International Autoantibody Standardization (IAS) initiatives, the optimization of diagnostic algorithms, the description and evaluation of novel disease-specific AABs as well as the development and introduction of novel assays into routine diagnostics. This review also highlights important developments of recent years, most notably the improvement in diagnosing and predicting the course of rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, and of autoimmune neurological, gastrointestinal and liver diseases; the potential diagnostic role of anti-DFS70 antibodies and tumor-associated AABs. Furthermore, some hot topics in autoimmunity regarding disease pathogenesis and management are described. PMID:27252254

  5. Comparison of autoantibodies to the collagen-like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus.

    Science.gov (United States)

    Wisnieski, J J; Jones, S M

    1992-03-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an apparent autoimmune disorder that resembles SLE. We previously showed that C1q precipitins in HUVS sera are IgG autoantibody to human C1q. We have compared HUVS anti-C1q autoantibody to a similar autoantibody in the serum of some patients with SLE. As with anti-C1q autoantibody in SLE sera, the HUVS autoantibody binds only to the collagen-like region (CLR) of C1q. In both HUVS and SLE, IgG2 is the predominant subclass of IgG autoantibody and IgM autoantibody to C1q is uncommon. In both diseases, anti-C1q autoantibodies bind preferentially to surface-adsorbed C1q or CLR fragments compared to these antigens in solution. Finally, when HUVS or SLE autoantibodies were added to CLR-coated wells already bound, respectively, by SLE or HUVS autoantibodies, no increases in CLR binding were observed, suggesting that HUVS and SLE autoantibodies to C1q bind to the same CLR epitope(s). PMID:1538123

  6. Treatment of Type B Insulin Resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies

    OpenAIRE

    "R. Malek; Chong, A. Y.; Lupsa, B. C.; Lungu, A. O.; Cochran, E. K.; Soos, M. A.; Semple, R.K.; Balow, J E; Gorden, P

    2010-01-01

    Background: Type B insulin resistance belongs to a class of diseases caused by an autoantibody to a cell surface receptor. Blockade of insulin action results in hyperglycemia, hypercatabolism, severe acanthosis nigricans, and hyperandrogenism in women. This rare autoimmune disorder has been treated with various forms of immunosuppression with mixed success.

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

    Science.gov (United States)

    Hagedorn, Peter H; Burton, Christopher M; Carlsen, Jørn; Steinbrüchel, Daniel; Andersen, Claus B; Sahar, Eli; Domany, Eytan; Cohen, Irun R; Flyvbjerg, Henrik; Iversen, Martin

    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, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could 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. Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role for autoimmunity in chronic rejection leading to OB. PMID:20201985

  8. 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.

  9. Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia.

    Science.gov (United States)

    Ogishi, Masato; Yotsuyanagi, Hiroshi; Moriya, Kyoji; Koike, Kazuhiko

    2016-01-01

    Antibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG). Reconstructed single-domain antibodies were reactive to both HCV antigens and potentially liver-derived human proteins. Moreover, over the course of antiviral therapy, a substantial "de-evolution" of a distinct sub-repertoire was discovered, to which proteomically identified cryoprecipitation-prone autoantibodies belonged. This sub-repertoire was characterized by IGHJ6*03-derived, long, hydrophobic complementarity determining region (CDR-H3). This study provides a proof-of-concept of de novo mining of autoantibodies and corresponding autoantigen candidates in a disease-specific context in human, thus facilitating future reverse-translational research for the discovery of novel biomarkers and the development of antigen-specific immunotherapy against various autoantibody-related disorders. PMID:27403724

  10. Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin.

    Science.gov (United States)

    Pawar, Rahul D; Goilav, Beatrice; Xia, Yumin; Zhuang, Haoyang; Herlitz, Leal; Reeves, Westley H; Putterman, Chaim

    2014-09-01

    The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity. PMID:24971701

  11. 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

  12. Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis

    DEFF Research Database (Denmark)

    Landegren, Nils; Pourmousa Lindberg, Mina; Skov, Jakob; Hallgren, Åsa; Eriksson, Daniel; Lisberg Toft-Bertelsen, Trine; MacAulay, Nanna; Hagforsen, Eva; Räisänen-Sokolowski, Anne; Saha, Heikki; Nilsson, Thomas; Nordmark, Gunnel; Ohlsson, Sophie; Gustafsson, Jan; Husebye, Eystein S; Larsson, Erik; Anderson, Mark S; Perheentupa, Jaakko; Rorsman, Fredrik; Fenton, Robert A; Kämpe, Olle

    2016-01-01

    autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells....

  13. 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; Perrild, Hans; Laurberg, Peter; Krejbjerg, Anne; Ovesen, Lars; Bülow Pedersen, Inge; Rasmussen, Lone Banke; Knudsen, Nils

    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...

  14. 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...

  15. 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...

  16. Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia

    Science.gov (United States)

    Ogishi, Masato; Yotsuyanagi, Hiroshi; Moriya, Kyoji; Koike, Kazuhiko

    2016-01-01

    Antibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG). Reconstructed single-domain antibodies were reactive to both HCV antigens and potentially liver-derived human proteins. Moreover, over the course of antiviral therapy, a substantial “de-evolution” of a distinct sub-repertoire was discovered, to which proteomically identified cryoprecipitation-prone autoantibodies belonged. This sub-repertoire was characterized by IGHJ6*03-derived, long, hydrophobic complementarity determining region (CDR-H3). This study provides a proof-of-concept of de novo mining of autoantibodies and corresponding autoantigen candidates in a disease-specific context in human, thus facilitating future reverse-translational research for the discovery of novel biomarkers and the development of antigen-specific immunotherapy against various autoantibody-related disorders. PMID:27403724

  17. 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. PMID:26273437

  18. Intrathecal IgG synthesis and autoantibody-secreting cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Jensen, Claus V; Christiansen, Michael

    We studied intrathecal IgG synthesis and autoantibody-secreting cells in 148 patients with possible onset symptoms of MS (POSMS) or clinically definite MS (CDMS). In POSMS intrathecal synthesis of IgG oligoclonal bands and abnormalities on T2-weighted magnetic resonance imaging were associated bu...

  19. 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.

  20. Coexistence of autoimmune diseases and autoantibodies in patients with myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Sibel Tamer

    2016-01-01

    Conclusions: MG has an increased frequency of coexisting ADs. Autoantibodies that are characteristic for ADs can be found in the patients without the presence of any of the clinical findings of ADs. Clinical attention towards the management of ADs is especially needed during the follow-up of patients with MG.

  1. Identification of Tetraspanin-7 as a Target of Autoantibodies in Type 1 Diabetes.

    Science.gov (United States)

    McLaughlin, Kerry A; Richardson, Carolyn C; Ravishankar, Aarthi; Brigatti, Cristina; Liberati, Daniela; Lampasona, Vito; Piemonti, Lorenzo; Morgan, Diana; Feltbower, Richard G; Christie, Michael R

    2016-06-01

    The presence of autoantibodies to multiple-islet autoantigens confers high risk for the development of type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA2, and zinc transporter-8), but the molecular identity of a fifth, a 38-kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography, and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from the sera of patients with diabetes before SDS-PAGE. Eluates from gel regions equivalent to 38 kDa were analyzed by liquid chromatography-tandem mass spectrometry for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity-purified sample, but not in the negative control. Only tetraspanin-7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy. PMID:26953162

  2. 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.

  3. 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...

  4. The impact of genes on the occurrence of autoantibodies in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Svendsen, Anders J; Hjelmborg, Jacob V; Kyvik, Kirsten O;

    2013-01-01

    -keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking. RESULTS: The...

  5. 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.

  6. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. PMID:25535268

  7. 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.

  8. Autoantibodies against G-Protein-Coupled Receptors Modulate Heart Mast Cells

    Institute of Scientific and Technical Information of China (English)

    Ludmila Okruhlicova; Rosemarie Morwinski; Wolfgang Schulze; Sabine Bartel; Peter Weismann; Narcisa Tribulova; Gerd Wallukat

    2007-01-01

    Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against α1-adrenoceptor and angiotensin Ⅱ AT1-receptor,agonist phenylephrine and angiotensin Ⅱ, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-α. The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence (p<0.05) and their enlarged diameters of the mast cells when compared to age-matched ones.In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls (p<0.01).In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones (p<0.001). Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.

  9. 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

    2015-12-01

    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

  10. Binding Affinity and Specificity of Neuromyelitis Optica Autoantibodies to Aquaporin-4 M1/M23 Isoforms and Orthogonal Arrays*

    OpenAIRE

    Crane, Jonathan M.; Lam, Chiwah; Rossi, Andrea; Gupta, Tripta; Bennett, Jeffrey L.; Verkman, A S

    2011-01-01

    Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-r...

  11. 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

  12. Prevalence and clinical significance of anti-lactoferrin autoantibodies in inflammatory bowel diseases and primary sclerosing cholangitis

    NARCIS (Netherlands)

    Roozendaal, C; Horst, G; Pogany, K; Kleibeuker, JH; Haagsma, EB; Limburg, PC; Kallenberg, CGM; Van Millegen de Wit, AWM; Spik, G; Legrand, D; Mazurier, J; Pierce, A; Perraudin, JP

    1998-01-01

    Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes. Antibodies with specificity for proteinase 3 and myeloperoxidase are seromarkers for systemic vasculitides. ANCA with specificity for lactoferrin were described in p

  13. Autoantibodies in children with alopecia areata from various radioecological areas of Belarus

    International Nuclear Information System (INIS)

    Alopecia areata (AA) is a nonscarring form of hair loss in humans. The most widely held belief is that AA is an autoimmune disease. After Chernobyl accident there has been an increase in autoimmunity pathology in Belarus including AA. The aim of the study was to asses the prevalence of autoantibodies in children with AA from various radioecological areas of Belarus. 87 patients (mean age - 10.3 +- 0.4) with AA were included in this study. 250 healthy children of the same age were studied as a control. Hair follicle antibodies (AB-HF) were measured by Western immunoblotting. Autoantibodies to thyroidperoxidase (AB-TPO) and thyroglobuline (AB-TG) were measured by radioimmunoassay using Medipan diagnostic kits. Autoantibodies to DNA were detected by immunopresipitation assay. We divided all children with AA on three groups: 1 - 14 children from noncontaminated area; 2 - 39 children from radio contaminated region and 3- patients from Minsk-city. The frequency of positive AB-TG in patients from group 2 (12%) was significantly higher in comparison to group 1 and 3 (0%). The proportion of children positive for both AB-TPO and AB-TG also was higher in group from contaminated area (8% vs 0%, 0%, p<0.001). There was significant difference in the incidence of AB-DNA between children from Minsk-city and children from non contaminated area (18.5% vs 0%, p<0.05). The frequency of positive both AB-TPO and AB-DNA in group 2 (6.9%) was almost the same as in the group 3 (7.1%). The prevalence of non-specific for AA autoantibodies was significantly higher in patients from radio contaminated area than in children from non contaminated region (44.9% vs 9%, p<0,001). The prevalence of specific hair follicle autoantibodies was significantly higher in children from contaminated region than patients from non contaminated area (50% vs 18%, p<0.05). Positive levels of were found in 36% of patients from Minsk-city. The increase of frequency specific and non-specific autoantibodies in children

  14. An autoantibody against Nε-(carboxyethyl)lysine (CEL): Possible involvement in the removal of CEL-modified proteins by macrophages

    International Nuclear Information System (INIS)

    Highlights: → A higher amount of autoantibody against CEL than that of other AGEs was observed in human plasma. → The purified human anti-CEL autoantibody specifically reacted with CEL. → Anti-CEL antibody accelerated the uptake of 125I-CEL-HSA by macrophage in vitro. → Endocytic uptake of 125I-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 Nε-(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 125I-labeled CEL-HSA was injected into the tail vein of mice, accumulation of 125I-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.

  15. High-Affinity Binding of Remyelinating Natural Autoantibodies to Myelin-Mimicking Lipid Bilayers Revealed by Nanohole Surface Plasmon Resonance

    OpenAIRE

    Wittenberg, Nathan J.; Im, Hyungsoon; Xu, Xiaohua; Wootla, Bharath; Watzlawik, Jens; Warrington, Arthur E.; Rodriguez, Moses; Oh, Sang-Hyun

    2012-01-01

    Multiple sclerosis is a progressive neurological disorder that results in the degradation of myelin sheaths that insulate axons in the central nervous system. Therefore promotion of myelin repair is a major thrust of multiple sclerosis treatment research. Two mouse monoclonal natural autoantibodies, O1 and O4, promote myelin repair in several mouse models of multiple sclerosis. Natural autoantibodies are generally polyreactive and predominantly of the IgM isotype. The prevailing paradigm is t...

  16. Anti-Tribbles homolog 2 (TRIB2) autoantibodies in narcolepsy are associated with recent onset of cataplexy

    DEFF Research Database (Denmark)

    Kawashima, Minae; Lin, Ling; Tanaka, Susumu; Jennum, Poul; Knudsen, Stine; Nevsimalova, Sona; Plazzi, Giuseppe; Mignot, Emmanuel

    2010-01-01

    Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases.......Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases....

  17. Localization of the discontinous immunodominant region recognized by human anti-thyroperoxidase autoantibodies in autoimmune thyroid diseases

    OpenAIRE

    Bresson, Damien; Cerutti, Martine; Devauchelle, Gerard; Pugnière, Martine; Roquet, Françoise; Bès, Cédric; Bossard, Carine; Chardès, Thierry; Péraldi-Roux, Sylvie

    2003-01-01

    The discontinuous immunodominant region (IDR) recognized by autoantibodies directed against the thyroperoxidase (TPO) molecule, a major autoantigen in autoimmune thyroid diseases, has not yet been completely localized. By using peptide phage-displayed technology, we identified three critical motifs, LXPEXD, QSYP, and EX(E/D)PPV, within selected mimotopes which interacted with the human recombinant anti-TPO autoantibody (aAb) T13, derived from an antibody phage-displayed library obtained from ...

  18. Pemphigus vegetans Neumann type with anti-desmoglein and anti-periplakin autoantibodies.

    Science.gov (United States)

    Cozzani, Emanuele; Christana, Konstantina; Mastrogiacomo, Alessandro; Rampini, Paolo; Drosera, Massimo; Casu, Massimo; Murialdo, Giovanni; Parodi, Aurora

    2007-01-01

    Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating lesions in the folds and mouth and by the presence of autoantibodies against desmoglein 3. We describe two Caucasian patients with pemphigus vegetans, one of them presented antibodies to desmoglein 3 and 1 and the other one to desmoglein 3. Both patients also had circulating antibodies against a 190 kDa protein co-migrating with periplakin. Anti-periplakin reactivity is usually detected in paraneoplastic pemphigus, while it has never been reported in pemphigus vegetans. Our observation enlarges the spectrum of autoantibodies which may be associated with pemphigus vegetans. However, the pathophysiological significance of anti-periplakin reactivity in this pemphigus variant remains to be determined. PMID:17951135

  19. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin; Hesse, Dan; Bendtzen, Klaus; Nielsen, Claus H

    2011-01-01

    -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 <0.009) and MS severity score (p <0.05), but not with disease activity as determined by the number of gadolinium......-enhanced lesions. The patients were followed for up to 26 months, during which the BAFF levels remained elevated without association to increased disease activity. IFN-beta therapy caused an increase in plasma BAFF levels after both 3 and 6 months of therapy (p <0.002). However, an 11% decrease in IgM and a 33...

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

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher Malcolm; Carlsen, Jørn;

    2010-01-01

    SUMMARY: 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, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS...... independent test patients. Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role...

  1. 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, and...... used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could be....... Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role for autoimmunity in...

  2. 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.

  3. Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients

    Institute of Scientific and Technical Information of China (English)

    Miao Li; Weiheng Su; Jie Wang; Francesco Pisani; Antonio Frigeri; Tonghui Ma

    2013-01-01

    In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast (V79) cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.

  4. Immunoadsorber for specific apheresis of autoantibodies in the treatment of bullous pemphigoid.

    Science.gov (United States)

    Mersmann, Michael; Dworschak, Jenny; Ebermann, Kristin; Komorowski, Lars; Schlumberger, Wolfgang; Stöcker, Winfried; Zillikens, Detlef; Probst, Christian; Schmidt, Enno

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies against two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. As the pathogenic relevance of antibodies against the immunodominant NC16A domain of BP180 has been clearly demonstrated, specific removal of these antibodies should be a rational therapeutic approach. Here, we evaluated three recombinant forms of bacterially produced BP180 NC16A, a monomer, trimer, and tetramer, together with different matrices for their efficacy to specifically adsorb autoantibodies from BP plasma samples. An adsorber consisting of NC16A-trimer coupled to NHS-activated Sepharose 4 Fast Flow revealed satisfying adsorption rates and a high specificity. The NC16A-trimer adsorber was regenerable and autoclavable. It has the potential to be used for specific immunoadsorption to treat severe and refractory BP and other pemphigoid diseases associated with BP180 NC16A reactivity. PMID:26498290

  5. Autoantibodies to the mitochondrial RNA processing (MRP) complex also known as Th/To autoantigen.

    Science.gov (United States)

    Mahler, Michael; Fritzler, Marvin J; Satoh, Minoru

    2015-03-01

    Antinuclear antibodies (ANA) represent valuable biomarkers in the diagnosis of systemic sclerosis (SSc) being present in the vast majority of the patients. Besides anti-topoisomerase I, anti-centromere and anti-RNA polymerase III antibodies as the main specificities, several other autoantibodies can be present in SSc patients including autoantibodies targeting the PM/Scl complex (also known as the exosome), U3-RNP/fibrillarin and the Th/To autoantigens. Anti-Th/To antibodies are one of the specificities that reportedly show homogenous nucleolar staining in conventional indirect immunofluorescence (IIF) ANA tests. Almost all protein components of the mitochondrial RNA processing (MRP) and the evolutionarily related RNase P complex have been reported to be the target of anti-Th/To antibodies in systemic autoimmune rheumatic disease (SARD) patients. However, Rpp25, Rpp38 and hPop1 have been described as the main autoantigen. PMID:25462581

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

    OpenAIRE

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

    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...

  7. Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.

    OpenAIRE

    Hoet, R M; Boerbooms, A M; Arends, M.; Ruiter, D J; van Venrooij, W J

    1991-01-01

    The antiperinuclear factor, an autoantibody specific for rheumatoid arthritis, was found in 51/63 (81%) patients with rheumatoid arthritis by indirect immunofluorescence on human buccal mucosa cells. The sensitivity of the antiperinuclear factor test was increased by pretreating the buccal mucosa cells with 0.5% Triton-X100. The specificity of the test for rheumatoid arthritis as compared with control serum samples was maintained. The localisation of the perinuclear factor in the keratohyalin...

  8. Anti-rods/rings autoantibody generation in hepatitis C patients during interferon-α/ribavirin therapy

    OpenAIRE

    Keppeke, Gerson Dierley; Calise, S John; Chan, Edward KL; Andrade, Luis Eduardo C

    2016-01-01

    Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α (IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies dem...

  9. Serum soluble interleukin 2 receptor levels in anti-neutrophil cytoplasmic autoantibodies--positive systemic vasculitis.

    OpenAIRE

    Lai, K N; Lockwood, C. M.

    1993-01-01

    Systemic vasculitis is characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens (ANCA). The role of T-lymphocytes in systemic vasculitis remains uncertain. In the present study, we attempted to explore the role of T-lymphocytes in systemic vasculitis by measuring the serum soluble interleukin 2 receptor (sIL2R) levels in seven vasculitic patients and comparing the sequential measurements with the titres of ANCA which satisfactorily reflect the disease activity. The s...

  10. Anti-p21 autoantibodies detected in colorectal cancer patients: A proof of concept study

    OpenAIRE

    Bishehsari, Faraz; Gach, Johannes S.; Akagi, Naomi; Webber, Molly K; Bauer, Jessica; Jung, Barbara H.

    2014-01-01

    Whereas the presence of autoantibodies in cancer patients has been acknowledged, their diagnostic or therapeutic significance has yet to be established. This is due, at least in part, to the lack of robust screening techniques to detect and characterize such antibodies for further assessment. In this study, we screened colorectal cancer (CRC) patient sera for antibodies specifically targeting the key cell cycle inhibitory factor p21 encoded by the cyclin-dependent kinase inhibitor 1A (CDKN1A)...

  11. Analysis of the serum reproductive system related autoantibodies of infertility patients in Tianjin region of China

    OpenAIRE

    Huo, Yan; Xu, Yanying; Wang, Jianmei; Wang, Fang; Liu, Yu; Zhang, Yujuan; Zhang, Bumei

    2015-01-01

    Object: Reproductive system related autoantibodies have been proposed to be associated with natural infertility. However, large scale systematic analysis of these of antibodies has not been conducted. The aim of this study is to analyze the positive rate of antisperm antibody (ASAb), anti-endometrium antibody (EMAb), anti-ovary antibody (AOAb), anti-zona pellucida antibody (AZP) and anticardiolipin antibody (ACA) in infertility patients in Tianjin region of China. Methods: 1305 male and 1711 ...

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

    OpenAIRE

    Licarete Emilia; Ganz Susanne; Recknagel Martin J; Di Zenzo Giovanni; Hashimoto Takashi; Hertl Michael; Zambruno Giovanna; Hundorfean Gheorghe; Mudter Jonas; Neurath Markus F; Bruckner-Tuderman Leena; Sitaru Cassian

    2012-01-01

    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 wetl...

  13. TSH-receptor-autoantibody-titers in untreated toxic diffuse goitres - an early indicator of relapse

    International Nuclear Information System (INIS)

    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% <= F <= 20% also had to be classified as cases of Graves' disease. But in follow-up of those patients there as no difference of TRAK-titers with regard to relapse or spontaneous remission. IF TSH-receptor-autoantibodies were undetectable (TRAK-titers F <= 3%), most of the patients could be identified as disseminated autonomies when there were no simultaneous signs of Graves' ophthalmopathy or secondary clinical signs of immunologic Graves' disease. In these patients a prediction of relapse was also not possible. Very high TSH-reactor-autoantibody-titers in untreated Graves' disease could be a good predictor of possible relapse or severe course of disease, indicating the early need for ablative therapy. Low titers or negative titers in some cases of Graves' disease do not allow any prediction of relapse. The lack of TSH-receptor-autoantibodies - correlating very well with secondary clinical signs of disseminated autonomy - supports the indication for ablative therapy in most cases as well. (orig.)

  14. Peptides Targeting the Desmoglein 3 Adhesive Interface Prevent Autoantibody-induced Acantholysis in Pemphigus*

    OpenAIRE

    Heupel, Wolfgang-Moritz; Müller, Thomas; Efthymiadis, Athina; Schmidt, Enno; Drenckhahn, Detlev; Waschke, Jens

    2009-01-01

    Pemphigus vulgaris (PV) autoantibodies directly inhibit desmoglein (Dsg) 3-mediated transinteraction. Because cellular signaling also seems to be required for PV pathogenesis, it is important to characterize the role of direct inhibition in pemphigus acantholysis to allow establishment of new therapeutic approaches. Therefore, we modeled the Dsg1 and Dsg3 sequences into resolved cadherin structures and predicted peptides targeting the adhesive interface of both Dsg3 an...

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

    International Nuclear Information System (INIS)

    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

  16. Autoantibodies against basement membrane collagen type IV are associated with myocardial infarction

    OpenAIRE

    Olga McLeod; Pontus Dunér; Ann Samnegård; Per Tornvall; Jan Nilsson; Anders Hamsten; Eva Bengtsson

    2015-01-01

    Background: Collagen type IV is the major constituent of basement membranes underlying endothelial cells and is important for endothelial cell attachment and function. Autoantibodies against native collagen type IV have been found in various autoimmune diseases. Oxidation of LDL in the vascular wall results in the formation of reactive aldehydes, which could modify surrounding matrix proteins. Like oxidized LDL, these modified matrix proteins are likely to induce immune responses. We examined...

  17. Blocking and Binding Folate Receptor Alpha Autoantibodies Identify Novel Autism Spectrum Disorder Subgroups

    OpenAIRE

    Frye, Richard E; Delhey, Leanna; Slattery, John; Tippett, Marie; Wynne, Rebecca; Rose, Shannon; Kahler, Stephen G.; Bennuri, Sirish C.; Melnyk, Stepan; Sequeira, Jeffrey M.; Quadros, Edward

    2016-01-01

    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 and 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 characteristic...

  18. Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto's thyroiditis.

    OpenAIRE

    Jansson, R.; Karlsson, A; Dahlberg, P A

    1985-01-01

    Ten hypothyroid patients with Hashimoto's thyroiditis were treated with methimazole 30 mg in addition to thyroxine 0.15 mg daily. Another 10 hypothyroid patients with Hashimoto's thyroiditis were given thyroxine 0.15 mg alone. After 22 weeks of treatment significant decreases in thyroid microsomal autoantibody titres were observed in both groups (p less than 0.01). There was no difference in the mean change in titre between the two groups. When the patients treated with methimazole were subse...

  19. 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.

  20. Significance of Myositis Autoantibody in Patients with Idiopathic Interstitial Lung Disease

    OpenAIRE

    Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo; Kang, Eun-Suk

    2015-01-01

    Purpose Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. Materials and Methods A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We a...

  1. THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity.

    Science.gov (United States)

    Larsen, Christopher P; Cossey, L Nicholas; Beck, Laurence H

    2016-04-01

    Thrombospondin type I domain-containing 7A (THSD7A) is a known antigenic target of autoantibodies leading to primary membranous glomerulopathy and was reported to account for ~10% of phospholipase A2 receptor (PLA2R)-negative membranous glomerulopathy. It has been proposed that PLA2R and THSD7A autoantibodies are mutually exclusive in membranous glomerulopathy. We validated an immunohistochemical assay to investigate for THSD7A-associated membranous glomerulopathy and utilized it in 258 consecutive native kidney biopsies, which showed membranous glomerulopathy in our laboratory, with the exception of membranous lupus nephritis. Membranous glomerulopathy stained positive for THSD7A-only in 7 (3%) cases, PLA2R-only in 141 (55%) cases, and showed dual positivity for THSD7A and PLA2R in 2 (1%) cases. Serologic testing for antibodies to PLA2R and THSD7A was performed in a subset of these patients. There was 100% correlation between positive THSD7A and/or PLA2R tissue staining and the presence of the corresponding autoantibodies in the serum including the two cases with dual positive THSD7A and PLA2R antibodies. We describe and provide a protocol for detection of THSD7A-associated membranous glomerulopathy in clinical practice. The cases with dual THSD7A and PLA2R positivity show that these autoantibodies are not mutually exclusive. They also emphasize the importance of using a panel-based approach when subtyping membranous glomerulopathy as a patient could conceptually be identified and treated based on anti-PLA2R titers, but still have anti-THSD7A antibodies driving persistent disease. PMID:26847174

  2. Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane

    OpenAIRE

    1994-01-01

    Intraperitoneal injection of pristane (2,6,10,14 tetramethylpentadecane) is a standard technique for obtaining monoclonal antibody-enriched ascitic fluid. However, pristane also induces plasmacytomas and an erosive arthritis resembling rheumatoid arthritis in BALB/c mice, probably as a consequence of enhanced interleukin 6 production. We report here that the production of autoantibodies characteristic of systemic lupus erythematosus (SLE) is a further consequence of injecting pristane in BALB...

  3. A Hypothesis Concerning a Potential Involvement of Ceramide in Apoptosis and Acantholysis Induced by Pemphigus Autoantibodies

    OpenAIRE

    Bollag, Wendy B.

    2010-01-01

    Autoimmune diseases affect more than 50 million Americans, resulting in significant healthcare costs. Most autoimmune diseases occur sporadically; however, endemic pemphigus foliaceus (EPF) is an autoimmune skin disease localized to specific geographic loci. EPF, and the related diseases pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are characterized by skin lesions and autoantibodies to molecules found on epidermal keratinocytes. A variant of EPF in patients from El Bagre, Colombia, ...

  4. Non-organ-specific Autoantibodies and CMV Infection in Renal Transplant Recipients with or without Rejection

    OpenAIRE

    R. Cavallo; F. Giacchino; G. P. Segoloni; C. Merlino; F. Sidoti; S. Margio; G. A. Touscoz; M. Bergallo; Costa, C.

    2007-01-01

    Aim/Background: A relation between cytomegalovirus (CMV) infection and development of non-organ-specific autoantibodies (NOSAs) has been reported in several studies and it has been hypothesized that CMV and NOSAs may be involved in the development of rejection in transplant recipients. Aim of this study was to investigate the presence of NOSAs, relation to CMV infection and development of acute or chronic rejection in a population of renal transplant recipients. Material/Methods: The presence...

  5. 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; Diamant, M; Nansen, A; Rieneck, K; Otterness, I G; Bendtzen, K

    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...

  6. A case of subepidermal blistering disease with autoantibodies to multiple laminin subunits who developed later autoantibodies to alpha-5 chain of type IV collagen associated with membranous glomerulonephropathy.

    Science.gov (United States)

    Sueki, Hirohiko; Sato, Yoshinori; Ohtoshi, Shinpei; Nakada, Tokio; Yoshimura, Ashio; Tateishi, Chiharu; Borza, Dorin-Bogdan; Fader, William; Ghohestani, Reza F; Hirako, Yoshiaki; Koga, Hiroshi; Ishii, Norito; Tsuchisaka, Atsunari; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi

    2015-09-01

    We report a 68-year-old Japanese female patient with subepidermal blistering disease with autoantibodies to multiple laminins, who subsequently developed membranous glomerulonephropathy. At skin disease stage, immunofluorescence demonstrated IgG anti-basement membrane zone antibodies reactive with dermal side of NaCl-split skin. Immunoblotting of human dermal extract, purified laminin-332, hemidesmosome-rich fraction and laminin-521 trimer recombinant protein (RP) detected laminin γ-1 and α-3 and γ-2 subunits of laminin-332. Three years after skin lesions disappeared, nephrotic symptoms developed. Antibodies to α-3 chain of type IV collagen (COL4A3) were negative, thus excluding the diagnosis of Goodpasture syndrome. All anti-laminin antibodies disappeared. Additional IB and ELISA studies of RPs of various COL4 chains revealed reactivity with COL4A5, but not with COL4A6 or COL4A3. Although diagnosis of anti-laminin γ-1 (p200) pemphigoid or anti-laminin-332-type mucous membrane pemphigoid could not be made, this case was similar to previous cases with autoantibodies to COL4A5 and/or COL4A6. PMID:25633161

  7. 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.

  8. A Hypothesis Concerning a Potential Involvement of Ceramide in Apoptosis and Acantholysis Induced by Pemphigus Autoantibodies

    Directory of Open Access Journals (Sweden)

    Wendy B. Bollag

    2010-01-01

    Full Text Available Autoimmune diseases affect more than 50 million Americans, resulting in significant healthcare costs. Most autoimmune diseases occur sporadically; however, endemic pemphigus foliaceus (EPF is an autoimmune skin disease localized to specific geographic loci. EPF, and the related diseases pemphigus vulgaris (PV and pemphigus foliaceus (PF, are characterized by skin lesions and autoantibodies to molecules found on epidermal keratinocytes. A variant of EPF in patients from El Bagre, Colombia, South America, has recently been reported to be distinct from previously described loci in Brazil and Tunisia epidemiologically and immunologically. As in PF and EPF, El Bagre EPF patients exhibit autoantibodies towards desmoglein-1, a cell adhesion molecule critical for maintaining epidermal integrity. An association of El Bagre EPF with sun exposure has been detected, and ultraviolet irradiation also exacerbates symptoms in PV, PF and EPF. Our hypothesis is that: (1 the autoantibodies generate pathology through an alteration in ceramide metabolism in targeted keratinocytes, resulting in apoptosis and/or cell death and acantholysis, but only when the cell's ability to metabolize ceramide is exceeded, and (2 apoptosis in response to this altered ceramide metabolism is initiated and/or exacerbated by other agents that increase ceramide levels, such as cytokines, ultraviolet irradiation, and senescence.

  9. Label-free nanoplasmonic sensing of tumor-associate autoantibodies for early diagnosis of colorectal cancer.

    Science.gov (United States)

    Soler, Maria; Estevez, M-Carmen; Villar-Vazquez, Roi; Casal, J Ignacio; Lechuga, Laura M

    2016-08-01

    Colorectal cancer is treatable and curable when detected at early stages. However there is a lack of less invasive and more specific screening and diagnosis methods which would facilitate its prompt identification. Blood circulating autoantibodies which are immediately produced by the immune system at tumor appearance have become valuable biomarkers for preclinical diagnosis of cancer. In this work, we present the rapid and label-free detection of colorectal cancer autoantibodies directly in blood serum or plasma using a recently developed nanoplasmonic biosensor. Our nanoplasmonic device offers sensitive and real-time quantification of autoantibodies with excellent selectivity and reproducibility, achieving limits of detection around 1 nM (150-160 ng mL(-1)). A preliminary evaluation of clinical samples of colorectal cancer patients has shown good correlation with ELISA. These results demonstrate the reliability of the nanobiosensor strategy and pave the way towards the achievement of a sensitive diagnostic tool for early detection of colorectal cancer. PMID:27265902

  10. Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System.

    Science.gov (United States)

    van Coevorden-Hameete, Marleen H; Titulaer, Maarten J; Schreurs, Marco W J; de Graaff, Esther; Sillevis Smitt, Peter A E; Hoogenraad, Casper C

    2016-01-01

    Autoimmune encephalitis (AIE) is a group of disorders in which autoantibodies directed at antigens located on the plasma membrane of neurons induce severe neurological symptoms. In contrast to classical paraneoplastic disorders, AIE patients respond well to immunotherapy. The detection of neuronal surface autoantibodies in patients' serum or CSF therefore has serious consequences for the patients' treatment and follow-up and requires the availability of sensitive and specific diagnostic tests. This mini-review provides a guideline for both diagnostic and research laboratories that work on the detection of known surface autoantibodies and/or the identification of novel surface antigens. We discuss the strengths and pitfalls of different techniques for anti-neuronal antibody detection: (1) Immunohistochemistry (IHC) and immunofluorescence on rat/primate brain sections; (2) Immunocytochemistry (ICC) of living cultured hippocampal neurons; and (3) Cell Based Assay (CBA). In addition, we discuss the use of immunoprecipitation and mass spectrometry analysis for the detection of novel neuronal surface antigens, which is a crucial step in further disease classification and the development of novel CBAs. PMID:27303263

  11. Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Marleen eVan Coevorden-Hameete

    2016-05-01

    Full Text Available Autoimmune encephalitis (AIE is a group of disorders in which autoantibodies directed at antigens located on the plasma membrane of neurons induce severe neurological symptoms. In contrast to classical paraneoplastic disorders, AIE patients respond well to immunotherapy. The detection of neuronal surface autoantibodies in patients’ serum or CSF therefore has serious consequences for the patients’ treatment and follow-up and requires the availability of sensitive and specific diagnostic tests. This mini-review provides a guideline for both diagnostic and research laboratories that work on the detection of known surface autoantibodies and/or the identification of novel surface antigens. We discuss the strengths and pitfalls of different techniques for anti-neuronal antibody detection: 1 Immunohistochemistry and immunofluorescence on rat/ primate brain sections, 2 Immunocytochemistry of living cultured hippocampal neurons, 3 Cell Based Assay (CBA. In addition, we discuss the use of immunoprecipitation and mass spectrometry analysis for the detection of novel neuronal surface antigens, which is a crucial step in further disease classification and the development of novel CBAs.

  12. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2011-01-01

    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

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

    International Nuclear Information System (INIS)

    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

  14. 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.

  15. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample

    OpenAIRE

    Evans, Michele; Sanders, Jane; Tagami, Tetsuya; Sanders, Paul; Young, Stuart; Roberts, Emma; Wilmot, Jane; Hu, Xiaoling; Kabelis, Katarzyna; Clark, Jill; Holl, Sabrina; Richards, Tonya; Collyer, Alastair; Furmaniak, Jadwiga; Rees Smith, Bernard

    2010-01-01

    Abstract Objective: Patients who appear to have both stimulating and blocking TSHR autoantibodies in their sera have been described but the two activities have not been separated and analysed. We now describe the isolation and detailed characterisation of a blocking type TSHR monoclonal autoantibody and a stimulating type TSHR monoclonal autoantibody from a single sample of peripheral blood lymphocytes. Design, Patients and Measurements: Two heterohybridoma cell lines secreting ...

  16. 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 J; Chen, Ning; Sellebjerg, Finn;

    2009-01-01

    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....

  17. 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....

  18. Are Agonistic Autoantibodies against G-Protein Coupled Receptors Involved in the Development of Long-Term Side Effects of Tumor Chemotherapy?

    Science.gov (United States)

    Haberland, Annekathrin; Santos, Robson A S; Schimke, Ingolf; Wallukat, Gerd

    2013-01-01

    Metabolic syndrome and cardiomyopathies are long-term consequences of chemo- and radiotherapy and develop long after completing the initial tumor treatment. The slow progression of such late effects might be an indication of the involvement of autoimmune processes in the development of such follow-up consequences. Functionally active autoantibodies, which permanently stimulate relevant cell receptors, might be a crucial component. Here, we report the detection of functionally active agonistic autoantibodies such as the autoantibody against the adrenergic alpha1-receptor, the muscarinic M2-receptor, and the newly discovered autoantibody against the Mas-receptor in the plasma of a cancer survivor following chemotherapy treatment. PMID:23569443

  19. 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

  20. Autoantibody production in chronic idiopathic urticaria is not associated with Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Atta A.M.

    2004-01-01

    Full Text Available Chronic idiopathic urticaria (CIU is a dermatological syndrome, characterized by raised erythematous skin lesions, that affects 20% of the general population and has been associated with autoimmunity. However, some reports have also suggested a close relationship between CIU and Helicobacter pylori infection, which is endemic in developing countries and associated with chronic gastritis, peptic ulcer disease, and gastric carcinoma. In the present study, we investigated the occurrence of autoantibodies in sera from 23 CIU subjects infected with H. pylori and from 23 CIU subjects without this infection. The presence of anti-thyroid antibodies was determined by indirect hemagglutination assay and the presence of autoantibodies to IgE and C1INH was determined by ELISA. Antibodies to thyroid antigens were detected at low titers from 100 to 400 in three of 23 (13% CIU-infected subjects and in four of 23 (17% CIU-noninfected subjects. The titers of anti-IgE autoantibodies were similar in these CIU groups, presenting absorbances of 1.16 ± 0.09 and 1.07 ± 0.16, respectively, while a titer of 1.14 ± 0.15 was detected in the healthy control group. The concentration of anti-C1INH autoantibodies was the same in the CIU-infected and -noninfected subjects (7.28 ± 1.31 and 7.91 ± 2.45 ng/ml, respectively, and was 7.20 ± 2.25 ng/ml in the healthy control group. However, the serum levels of complexed anti-C1INH antibodies were increased in CIU-infected subjects compared to CIU-noninfected subjects and healthy controls with an absorbance of 1.51 ± 0.21 vs 1.36 ± 0.16 and 1.26 ± 0.23, respectively (P < 0.05, indicating an impaired clearance of immune complexes in CIU-infected patients. In conclusion, no correlation was observed between H. pylori infection and autoantibody production in CIU patients consistent with reports of clinical studies.

  1. Surface plasmon resonance reveals a different pattern of proinsulin autoantibodies concentration and affinity in diabetic patients.

    Directory of Open Access Journals (Sweden)

    Aldana Trabucchi

    Full Text Available Type 1 diabetes mellitus (DM is characterized by autoimmune aggression against pancreatic beta cells resulting in absolute deficiency of insulin secretion. The first detectable sign of emerging autoimmunity during the preclinical asymptomatic period is the appearance of diabetes-related autoantibodies. In children at risk for type 1 DM, high-affinity Insulin autoantibodies reactive to proinsulin, are associated with diabetes risk. Autoantibodies are usually measured by radioligand binding assay (RBA that provides quasi-quantitative values reflecting potency (product between concentration and affinity of specific autoantibodies. Aiming to improve the characterization of the specific humoral immune response, we selected surface plasmon resonance (SPR as an alternative method to measure proinsulin autoantibodies (PAA. This novel technology has allowed real time detection of antibodies interaction and kinetic analysis. Herein, we have employed SPR to characterize the PAA present in sera from 28 childhood-onset (mean age 8.31±4.20 and 23 adult-onset diabetic patients (≥65 years old, BMI<30 in terms of concentration and affinity. When evaluating comparatively samples from both groups, childhood-onset diabetic patients presented lower PAA concentrations and higher affinities (median 67.12×10(-9 M and 3.50×10(7 M(-1, respectively than the adults (median 167.4×10(-9 M and 0.84×10(7 M(-1, respectively. These results are consistent with those from the reference method RBA (Standard Deviation score median 9.49 for childhood-onset group and 5.04 for adult-onset group where the binding can be directly related to the intrinsic affinity of the antibody, suggesting that there is a different etiopathogenic pathway between both types of clinical presentation of the disease. This technology has shown to be a useful tool for the characterization of PAAs parameters as an alternative to radioimmunoassay, with high versatility and reproducibility associated to

  2. The measurement of TSH-receptor autoantibodies in human serum by radioreceptor assay

    International Nuclear Information System (INIS)

    TSH receptor autoantibodies (TRAB) are valuable in Graves' disease with a sensitivity of 85% and a specificity of 80%. Autoantibodies levels decrease progressively with antithyroid drugs treatment or after thyroidectomy. The predictive value of the level of TSH receptor autoantibodies is diversely appreciated. Nevertheless, the vast majority of the studies agrees on the fact that high levels of TSH receptor autoantibodies predict a relapse. The feto-placental transfer of these antibodies could explain congenital hyperthyroidism of newborns from mother affected by Graves' disease. These antibodies are present in certain cases of Hashimoto thyroiditis, subacute thyroiditis or silent thyroiditis in phase of thyrotoxicosis. In Vietnam, first time we have researched determination of TRAB levels in the non disease and the Graves' disease, after treatment of antithyroid drugs and after thyroidectomy. We imported TRAB - Kit from CIS bio international France. The principle of Radioreceptor assay (RRA ) is following: TR - Ab kit utilizes a principle of competition between TSH receptor autoantibodies present in the sample and bovine TSH radiolabelled with 125-I, facing a fixed and limited amount of soluble porcine TSH receptors. The more TSH receptor autoantibodies are present in the sample, the less 125-I- TSH is bound to the soluble TSH receptors. Free and bound fractions are separated in adding PEG solution followed by a centrifugation. Results are calculated from a calibration curve (U/l). The samples were counted by the multi crystal gamma counter Oakfield which was supplied from IAEA (Years 2000). This is the first study in Vietnam, the concentration of TSH receptor autoantibodies (TRAB) was determined by radioreceptor assay (RRA) on 30 normal subjects and 30 Grave's disease subjects. The normal range is 1,4 □ 0.6 U/l. Max of normal is 2.99U/l. Min of normal is 3.38U/l .There are 11 males and 29 females with age from 15 to 50 years old. Mean of Graves' disease is 182U

  3. The Association among Antioxidant Enzymes, Autoantibodies, and Disease Severity Score in Systemic Lupus Erythematosus: Comparison of Neuropsychiatric and Nonneuropsychiatric Groups

    Directory of Open Access Journals (Sweden)

    Yu-Jih Su

    2014-01-01

    Full Text Available Background. Antioxidative capacity plays an important role in the severity of systemic lupus erythematosus (SLE, which is characterized by autoantibodies. This study aimed to determine the relationship among autoantibody titers, antioxidative stress reserve, and severity of SLE. Methods. The autoantibody titers, clinical markers, antioxidant enzyme levels, and disease activity index (SLEDAI-2k of 32 SLE patients and 16 healthy controls were compared. We also compared both the neuropsychiatric (NPSLE and nonneuropsychiatric (non-NPSLE groups. Results. Superoxide dismutase in red blood cells was significantly lower in the SLE than in the control group. CRP levels are significant higher in SLE patients than in control group (P=0.034. Among the autoantibodies, anti-U1RNP P=0.008, a-Sm P=0.027, and anti-ribosomal p P=0.028 significantly negatively correlated with glutathione levels. There has no significant correlation between SLE disease activity indexes (SLEDAI and levels of C3, C4, and antioxidant enzymes. Conclusions. Erythrocyte superoxide dismutase is significantly lower in both NPSLE and non-NPSLE groups. SLE patients have both higher CRP and autoantibodies level and decreased superoxide dismutase level than the healthy control group.

  4. Essential Requirement for IFN Regulatory Factor 7 in Autoantibody Production but Not Development of Nephritis in Murine Lupus.

    Science.gov (United States)

    Miyagawa, Fumi; Tagaya, Yutaka; Ozato, Keiko; Asada, Hideo

    2016-09-15

    Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the production of autoantibodies against nuclear components. Recent genetic studies of SLE patients have revealed that IFN regulatory factor (IRF) 7 gene polymorphisms are associated with an increased risk of SLE, but the precise role of IRF7 in SLE development is not fully understood. We investigated the role of IRF7 in the pathogenesis of SLE using a mouse model and saw a curious dissociation of autoantibody production and development of glomerulonephritis. SLE was chemically induced into IRF7-deficient mice, and glomerulonephritis with deposits of IgG and lipogranulomas were observed after 10 mo. However, these mice failed to produce anti-dsDNA, ssDNA, ribonucleoprotein, and Sm autoantibodies. Following the chemical induction, IRF7-deficient mice expressed substantially lower levels of IFN-stimulated genes than did wild-type mice, but NF-κB target genes were equally upregulated in both strains. Therefore, the type I IFN pathway seems critical for the autoantibody production, but the NF-κB activation is sufficient for the development of glomerulonephritis in this model. Our study thus demonstrates a specific requirement for IRF7 in autoantibody production and uncovers a new layer of complexity in the pathogenesis of SLE. PMID:27527596

  5. 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.

  6. Autoantibodies to histone, DNA and nucleosome antigens in canine systemic lupus erythematosus.

    Science.gov (United States)

    Monestier, M; Novick, K E; Karam, E T; Chabanne, L; Monier, J C; Rigal, D

    1995-01-01

    Dogs can develop systemic lupus erythematosus syndromes that are clinically similar to those seen in humans. In contrast, previous observations suggest differences in their autoantibody reactivity patterns against histones and DNA which are components of the nucleosome in chromatin. The objective of this study was to assess comprehensively the levels of autoantibodies against histone, DNA and nucleosome antigens in a population of lupus dogs. The specificities of antibodies in lupus and control dog sera were determined using IgM- and IgG-specific reagents in an ELISA against a variety of chromatin antigens. When compared with control sera, IgG antibodies to individual histones H1, H2A, H3 and H4 were significantly higher in the lupus group. In contrast, we did not detect IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosome in lupus dogs. There was no significant increase in any of the IgM specificities tested. Therefore, the reactivity pattern to nucleosome antigens in canine lupus is restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This stands in contrast with human and murine lupus, where autoantibodies are directed against a wide variety of nucleosomal determinants, suggesting that unique mechanisms lead to the expansion of anti-histone antibody clones in canine lupus. The high incidence of glomerulonephritis in dog lupus suggests that anti-DNA antibodies are not required for the development of this complication, whereas IgG anti-histone antibodies may be relevant to its pathogenesis. PMID:7529150

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

    International Nuclear Information System (INIS)

    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)

  8. A Role for Anti-BP180 Autoantibodies in Chronic Rhinosinusitis

    Science.gov (United States)

    Jeffe, Jill S.; Seshadri, Sudarshan; Hamill, Kevin J.; Huang, Julia He; Carter, Roderick; Suh, Lydia; Hulse, Kathryn; Norton, James; Conley, David B.; Chandra, Rakesh K.; Kern, Robert C.; Jones, Jonathan C.R.; Schleimer, Robert P.; Tan, Bruce K.

    2013-01-01

    Objectives CRS is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time PCR, Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluoresence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (p<0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS. PMID:24167818

  9. Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies

    Science.gov (United States)

    Albrecht, Inka; Wick, Cecilia; Hallgren, Åsa; Tjärnlund, Anna; Nagaraju, Kanneboyina; Andrade, Felipe; Thompson, Kathryn; Coley, William; Phadke, Aditi; Diaz-Gallo, Lina-Marcela; Bottai, Matteo; Nennesmo, Inger; Chemin, Karine; Herrath, Jessica; Johansson, Karin; Wikberg, Anders; Ytterberg, A. Jimmy; Zubarev, Roman A.; Danielsson, Olof; Krystufkova, Olga; Vencovsky, Jiri; Landegren, Nils; Wahren-Herlenius, Marie; Padyukov, Leonid; Kämpe, Olle; Lundberg, Ingrid E.

    2015-01-01

    Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1–negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM. PMID:26551678

  10. Mapping epitopes of U1-70K autoantibodies at single-amino acid resolution.

    Science.gov (United States)

    Haddon, David James; Jarrell, Justin Ansel; Diep, Vivian K; Wand, Hannah E; Price, Jordan V; Tangsombatvisit, Stephanie; Credo, Grace M; Mackey, Sally; Dekker, Cornelia L; Baechler, Emily C; Liu, Chih Long; Varma, Madoo; Utz, Paul J

    2015-01-01

    The mechanisms underlying development of ribonucleoprotein (RNP) autoantibodies are unclear. The U1-70K protein is the predominant target of RNP autoantibodies, and the RNA binding domain has been shown to be the immunodominant autoantigenic region of U1-70K, although the specific epitopes are not known. To precisely map U1-70K epitopes, we developed silicon-based peptide microarrays with >5700 features, corresponding to 843 unique peptides derived from the U1-70K protein. The microarrays feature overlapping peptides, with single-amino acid resolution in length and location, spanning amino acids 110-170 within the U1-70K RNA binding domain. We evaluated the serum IgG of a cohort of patients with systemic lupus erythematosus (SLE; n = 26) using the microarrays, and identified multiple reactive epitopes, including peptides 116-121 and 143-148. Indirect peptide ELISA analysis of the sera of patients with SLE (n = 88) revealed that ∼14% of patients had serum IgG reactivity to 116-121, while reactivity to 143-148 appeared to be limited to a single patient. SLE patients with serum reactivity to 116-121 had significantly lower SLE Disease Activity Index (SLEDAI) scores at the time of sampling, compared to non-reactive patients. Minimal reactivity to the peptides was observed in the sera of healthy controls (n = 92). Competitive ELISA showed antibodies to 116-121 bind a common epitope in U1-70K (68-72) and the matrix protein M1 of human influenza B viruses. Institutional Review Boards approved this study. Knowledge of the precise epitopes of U1-70K autoantibodies may provide insight into the mechanisms of development of anti-RNP, identify potential clinical biomarkers and inform ongoing clinical trails of peptide-based therapeutics. PMID:26333287

  11. Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander;

    2014-01-01

    Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels before clinical diagnosis, and their utility in cancer screening in t...

  12. 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 autoanti...

  13. Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria.

    Science.gov (United States)

    Kuzmina, Zoya; Gounden, Verena; Curtis, Lauren; Avila, Daniele; Rnp, Tiffani Taylor; Baruffaldi, Judy; Cowen, Edward W; Naik, Haley B; Hasni, Sarfaraz A; Mays, Jacqueline W; Mitchell, Sandra; Baird, Kristin; Steinberg, Seth M; Pavletic, Steven Z

    2015-02-01

    There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P antibodies were detected in 35% of patients. Prior rituximab therapy (n = 66) was associated with reduced presence of autoantibodies (48 vs. 66% P = 0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P = 0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD. PMID:25363867

  14. A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure

    DEFF Research Database (Denmark)

    Pedersen, I.B.; Laurberg, P.; Knudsen, N.; Jorgensen, T.; Perrild, H.; Ovesen, Lars; Rasmussen, Lone Banke

    2005-01-01

    autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism. Design A population study including 4649 randomly selected subjects. Measurements Blood tests were used to analyse for thyroid peroxidase......Objective Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid...... autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. Results Thyroid volume was categorized as small (<6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (<0.4 mIU/l) in 4.7%, normal (0...

  15. Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Laustsen, Julie K; Rasmussen, Tue K; Stengaard-Pedersen, Kristian;

    2014-01-01

    .0001). The sOX40/sOX40L ratio was decreased in eRA, and a low ratio at the time of adalimumab discontinuation was associated with increased DAS28CRP and risk of flare the following year. T cells in the synovial fluid had the highest expression of OX40, while monocytes and B cells were the main expressers of...... systems facilitate to drive disease activity and autoantibody production in RA. TRIAL REGISTRATION: Clincaltrials.gov NCT00660647, 10 April 2008....

  16. Anti-C1q Autoantibodies, Novel Tests, and Clinical Consequences

    OpenAIRE

    Mahler, Michael; van Schaarenburg, Rosanne A.; Trouw, Leendert A.

    2013-01-01

    Although anti-C1q autoantibodies have been described more than four decades ago a constant stream of papers describing clinical associations or functional consequences highlights that anti-C1q antibodies are still hot and happening. By far the largest set of studies focus on anti-C1q antibodies is systemic lupus erythematosus (SLE). In SLE anti-C1q antibodies associate with involvement of lupus nephritis in such a way that in the absence of anti-C1q antibodies it is unlikely that a flare in n...

  17. Prevalence of anti-retinal autoantibodies in different stages of Age-related macular degeneration

    OpenAIRE

    Adamus, Grazyna; Chew, Emily Y; Ferris, Frederick L.; Klein, Michael L.

    2014-01-01

    Background 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. Methods 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 diagno...

  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. 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 a......, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight...

  20. Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

    OpenAIRE

    Rebuffat, S A; MORIN, M; Nguyen, B; Castex, F; Robert, B.; Péraldi-Roux, S.

    2010-01-01

    Background: Thyroid cancers are difficult to treat due to their limited responsiveness to chemo- and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches. Results: We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4′) or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial d...

  1. Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in faroese children

    DEFF Research Database (Denmark)

    Osuna, Christa E; Grandjean, Philippe; Weihe, Pál; El-Fawal, Hassan A N

    2014-01-01

    to both neural (neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and non-neural (actin, desmin, and keratin) antigens were measured and the associations of these autoantibody concentrations with chemical exposures were assessed using...... linear regression. Age-7 blood-mercury concentrations were positively associated with titers of multiple neural- and non-neural-specific antibodies, mostly of the IgM isotype. Additionally, prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG and prenatal PFOS was negatively...

  2. 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.

  3. Antigenic heterogeneity of IgA anti-GBM disease: new renal targets of IgA autoantibodies.

    Science.gov (United States)

    Ho, Julie; Gibson, Ian W; Zacharias, James; Fervenza, Fernando; Colon, Selene; Borza, Dorin-Bogdan

    2008-10-01

    Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of alpha 3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the alpha 3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patient's IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the alpha 3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results. PMID:18752876

  4. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

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    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.

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

    OpenAIRE

    Suppiah, Aravind; Greenman, John

    2013-01-01

    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 discrepanci...

  6. Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism

    Directory of Open Access Journals (Sweden)

    Wills Sharifia

    2011-04-01

    Full Text Available Abstract Background Autism is a neurodevelopmental disorder characterized by impairments in social interaction and deficits in verbal and nonverbal communication, together with the presence of repetitive behaviors or a limited repertoire of activities and interests. The causes of autism are currently unclear. In a previous study, we determined that 21% of children with autism have plasma autoantibodies that are immunoreactive with a population of neurons in the cerebellum that appear to be Golgi cells, which are GABAergic interneurons. Methods We have extended this analysis by examining plasma immunoreactivity in the remainder of the brain. To determine cell specificity, double-labeling studies that included one of the calcium-binding proteins that are commonly colocalized in GABAergic neurons (calbindin, parvalbumin or calretinin were also carried out to determine which GABAergic neurons are immunoreactive. Coronal sections through the rostrocaudal extent of the macaque monkey brain were reacted with plasma from each of seven individuals with autism who had previously demonstrated positive Golgi cell staining, as well as six negative controls. In addition, brain sections from adult male mice were similarly examined. Results In each case, specific staining was observed for neurons that had the morphological appearance of interneurons. By double-labeling sections with plasma and with antibodies directed against γ-aminobutyric acid (GABA, we determined that all autoantibody-positive neurons were GABAergic. However, not all GABAergic neurons were autoantibody-positive. Calbindin was colabeled in several of the autoantibody-labeled cells, while parvalbumin colabeling was less frequently observed. Autoantibody-positive cells rarely expressed calretinin. Sections from the mouse brain processed similarly to the primate sections also demonstrated immunoreactivity to interneurons distributed throughout the neocortex and many subcortical regions. Some

  7. A Rapid Lateral Flow Immunoassay for the Detection of Tyrosine Phosphatase-Like Protein IA-2 Autoantibodies in Human Serum

    OpenAIRE

    Ingrid Kikkas; Roberto Mallone; Etienne Larger; Hervé Volland; Nathalie Morel

    2014-01-01

    Type 1 diabetes (T1D) results from the destruction of pancreatic insulin-producing beta cells and is strongly associated with the presence of islet autoantibodies. Autoantibodies to tyrosine phosphatase-like protein IA-2 (IA-2As) are considered to be highly predictive markers of T1D. We developed a novel lateral flow immunoassay (LFIA) based on a bridging format for the rapid detection of IA-2As in human serum samples. In this assay, one site of the IA-2As is bound to HA-tagged-IA-2, which is...

  8. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

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    Tao Cui

    Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

  9. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

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    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

  10. 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.

  11. 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.

  12. Dermatitis herpetiformis bodies and autoantibodies to noncutaneous organs and mitochondria in dermatitis herpetiformis

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2012-10-01

    Full Text Available Introduction: The precise nature of the previously described dermatitis herpetiformis bodies remains unknown.Aims: Our study was conducted to investigate the nature of dermatitis herpetiformis bodies in the skin in 7 cases of dermatitis herpetiformis, and to search for the presence of autoantibodies in other organsMethods: We utilized clinical, histopathologic, and immunologic methods to evaluate these patients.Results: Dermatitis herpetiformis bodies were found to be comprised of an amalgamation of immunoglobulins A and M, as well as molecules reactive with antibodies to armadillo repeat gene deleted in velo-cardio-facial syndrome, desmoplakins 1 and 2, and plakophilin 4. In addition, we found immunologic colocalization with selected autoantibodies associated with mitochondria in the skin, heart, kidney, and peripheral nerves. The dermatitis herpetiformis bodies did not demonstrate immunologic colocalization with tissue/epidermal transglutaminase.Conclusion: The complete biochemical nature of dermatitis herpetiformis bodies requires further characterization. Dermatitis herpetiformis bodies in these patients appear to be distinctly different than cytoid bodies. Further studies are required to determine if the antibodies to noncutaneous organs are pathogenic, and/or contribute to systemic morbility in dermatitis herpetiformis patients.

  13. Autoantibody profile and other immunological parameters in recurrent spontaneous abortion patients

    Directory of Open Access Journals (Sweden)

    U Shankarkumar

    2011-01-01

    Full Text Available 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 pregnant women from Mumbai western India. Fifty RSA patients with unknown cause and greater than three consecutive abortions along with 50 normal pregnant women were studied for various auto antibodies such as ANA, anti-dsDNA, ANCA, AECA, 2 micro globulin, anti-HLA antibodies and ACLA using immunofluorescence microlymphocytotoxicity and ELISA. Immunological parameters such as HLA class I monoclonal antibody expression, CD3 (T cell, CD19 (B cell, and CD56 (NK cell were estimated by flow cytometry. Results: The results revealed 34% positivity of all auto antibodies tested among patients. ANA(12%, ANCA (20%, AECA (24%, ACLA (8%, anti-dsDNA(0%, β2 microglobulin (14%, and anti-HLA antibodies(10% among RSA patients were identified. An increased expression of HLA class I specific monoclonal antibody (10% with HLA A3 (16% specificity were found to correlate with shared HLA alleles among the RSA couples. Among normal pregnant (control group ANA (2%, ANCA (2%, AECA (3%, ACLA (4% and increased expression of CD56 with reduced HLA class I monoclonal were observed. Conclusion: Our findings suggest a possible role of various autoantibodies along with the related immunological parameters underlying RSA.

  14. Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis.

    Science.gov (United States)

    Piccoli, Luca; Campo, Ilaria; Fregni, Chiara Silacci; Rodriguez, Blanca Maria Fernandez; Minola, Andrea; Sallusto, Federica; Luisetti, Maurizio; Corti, Davide; Lanzavecchia, Antonio

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies. PMID:26077231

  15. Significance of combined determination of multiple autoantibodies in patients with systemic lupus erythematosus

    International Nuclear Information System (INIS)

    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)

  16. Binding affinities of anti-acetylcholine receptor autoantibodies in myasthenia gravis

    International Nuclear Information System (INIS)

    Antibodies directed against acetylcholine (ACh) receptors are present in the sera of nearly 90% of patients with myasthenia gravis (MG), and are involved in the pathogenesis of this autoimmune disease. However, the antibody titers measured by the standard radioimmunoassay correspond poorly with the clinical severity of the disease. To determine whether this disparity could be accounted for by differences in the binding affinities of anti-ACh receptor antibodies in different patients, we have measured the binding affinities of these autoantibodies in 15 sera from MG patients. The affinity constants (K/sub o/), as determined by Scatchard analysis, were all in the range of 1010 M-1, comparable to the highest values reported in immunized animals. The affinity constants were truly representative of the population of autoantibodies detected by the radioimmunoassay, as shown by the remarkable linearity of the Scatchard plots (r2>0.90) and the close correlation between the antibody titers determined by extrapolation of the Scatchard plots and by saturation analysis (r = 0.99; p < 0.001). There was only a 6-fold variation in affinity constants measured in this series of patients despite widely differing antibody titers and severity of the disease. Factors other than the titer and affinity of anti-ACh receptor antibodies may correlate better with the clinical manifestations of MG

  17. Binding affinities of anti-acetylcholine receptor autoantibodies in myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Bray, J.J.; Drachman, D.B.

    1982-01-01

    Antibodies directed against acetylcholine (ACh) receptors are present in the sera of nearly 90% of patients with myasthenia gravis (MG), and are involved in the pathogenesis of this autoimmune disease. However, the antibody titers measured by the standard radioimmunoassay correspond poorly with the clinical severity of the disease. To determine whether this disparity could be accounted for by differences in the binding affinities of anti-ACh receptor antibodies in different patients, we have measured the binding affinities of these autoantibodies in 15 sera from MG patients. The affinity constants (K/sub o/), as determined by Scatchard analysis, were all in the range of 10/sup 10/ M/sup -1/, comparable to the highest values reported in immunized animals. The affinity constants were truly representative of the population of autoantibodies detected by the radioimmunoassay, as shown by the remarkable linearity of the Scatchard plots (r/sup 2/>0.90) and the close correlation between the antibody titers determined by extrapolation of the Scatchard plots and by saturation analysis (r = 0.99; p < 0.001). There was only a 6-fold variation in affinity constants measured in this series of patients despite widely differing antibody titers and severity of the disease. Factors other than the titer and affinity of anti-ACh receptor antibodies may correlate better with the clinical manifestations of MG.

  18. Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization.

    Science.gov (United States)

    Reed, Joanne H; Jackson, Jennifer; Christ, Daniel; Goodnow, Christopher C

    2016-06-27

    Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and >43% of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses. PMID:27298445

  19. 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

    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......-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...

  20. Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid-phase radioimmunoassay

    International Nuclear Information System (INIS)

    A solid-phase radioimmunoassay was developed to detect antibodies to liver membrane antigens in sera of patients with HBsAg-negative and -positive liver diseases and primary non-hepatic autoimmune diseases. Ten of fourteen patients with HBsAg-negative CAH had autoantibodies detected by RIA; negative results were obtained with sera of seven patients with HBsAg-positive acute and chronic liver diseases, six patients with miscellaneous liver diseases, including two patients with PBC, two healthy blood donors and seven patients with primary non-hepatic autoimmune diseases. Antibodies detected by RIA correlated with liver membrane autoantibodies (LMA) found by indirect immunofluorescence; no correlation was observed with AMA, ANA and SMA. Species-cross-reacting antibodies could be absorbed by preincubation with isolated plasma cell membranes prepared from rabbit livers. Liver membrane autoantibodies detected by RIA were directed against three different antigen fractions obtained from Sepharose 6B chromatography including LSP and LM-Ag. Only three of ten antibodies were directed against species-specific determinants; others cross-reacted with rabbit antigens. Only the antibody to LSP was organ-specific, all others cross-reacted with kidney proteins. Ferritin, human serum albumin and human plasma lipoprotein were excluded as target antigens. Although several sera reacted with identical molecules a remarkable heterogeneity of liver membrane autoantibodies was observed. (author)

  1. Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange

    DEFF Research Database (Denmark)

    Iversen, Rasmus; Mysling, Simon; Hnida, Kathrin;

    2014-01-01

    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...

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

    Science.gov (United States)

    Suwarnalata, Gunasekaran; Tan, Ai Huey; Isa, Hidayah; Gudimella, Ranganath; Anwar, Arif; Loke, Mun Fai; Mahadeva, Sanjiv; Lim, Shen-Yang; Vadivelu, Jamuna

    2016-01-01

    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. PMID:27100827

  3. Patient-derived Granulocyte/Macrophage Colony–Stimulating Factor Autoantibodies Reproduce Pulmonary Alveolar Proteinosis in Nonhuman Primates

    OpenAIRE

    Sakagami, Takuro; Beck, David; Uchida, Kanji; Suzuki, Takuji; Carey, Brenna C.; Nakata, Koh; Keller, Gary; Wood, Robert E.; Wert, Susan E.; Ikegami, Machiko; Whitsett, Jeffrey A.; Luisetti, Maurizio; Davies, Stella; Krischer, Jeffrey P; Brody, Alan

    2010-01-01

    Rationale: Granulocyte/macrophage colony–stimulating factor (GM-CSF) autoantibodies (GMAb) are strongly associated with idiopathic pulmonary alveolar proteinosis (PAP) and are believed to be important in its pathogenesis. However, levels of GMAb do not correlate with disease severity and GMAb are also present at low levels in healthy individuals.

  4. High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Kadota Jun-ichi

    2008-11-01

    Full Text Available Abstract Background The pathological diagnosis of idiopathic interstitial pneumonias (IIP by surgical lung biopsy is important for clinical decision-making. However, there is a need to use less invasive biomarkers to differentiate nonspecific interstitial pneumonia (NSIP from other IIP such as usual interstitial pneumonia (UIP. Heat shock protein (HSP 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is increased in various fibrotic diseases. We investigated the autoantibodies to HSP47 in IIPs. Methods We measured the serum levels of the autoantibodies to HSP47 in 38 patients with various forms of IIP [16 with idiopathic pulmonary fibrosis (IPF, 15 with idiopathic NSIP, 7 with cryptogenic organizing pneumonia (COP] and 18 healthy volunteers. Results The serum levels of autoantibodies to HSP47 in patients with idiopathic NSIP were significantly higher than in patients with IPF (P Conclusion We found high levels of anti-HSP47 autoantibody titers in sera of patients with idiopathic fibrosing NSIP compared with other IIPs and healthy volunteers.

  5. Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Kovacs, Katalin T; Kalluri, Sudhakar Reddy; Boza-Serrano, Antonio;

    2015-01-01

    BACKGROUND: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. OBJECTIVE: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute...

  6. Induction of anti-beta(2)-glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes

    NARCIS (Netherlands)

    Van Os, G. M. A.; Meijers, J. C. M.; Agar, C.; Seron, M. V.; Marquart, J. A.; Akesson, P.; Urbanus, R. T.; Derksen, R. H. W. M.; Herwald, H.; Morgelin, M.; De Groot, P. G.

    2011-01-01

    Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti-beta 2-glycoprotein I (beta 2-GPI) autoantibodies. beta 2-GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook conformation after binding to phospholip

  7. Clinical characteristics of patients with myositis and autoantibodies to different fragments of the Mi-2 beta antigen.

    NARCIS (Netherlands)

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

    2006-01-01

    OBJECTIVES: To assess the clinical implications of autoantibodies directed against different parts of the Mi-2 beta autoantigen in patients with myositis. METHODS: A systematic assessment of the clinical, laboratory, and histological characteristics of 48 anti-Mi-2 positive patients from six Europea

  8. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis - A prospective cohort study

    NARCIS (Netherlands)

    Gaalen, F.A. van; Linn-Rasker, S.P.; Venrooij, W.J.W. van; Jong, B.A. de; Breedveld, F.C.; Verweij, C.L.; Toes, R.E.M.; Huizinga, T.W.J.

    2004-01-01

    Objective. Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an

  9. IgG red blood cell autoantibodies in autoimmune hemolytic anemia bind to epitopes on red blood cell membrane band 3 glycoprotein

    International Nuclear Information System (INIS)

    Red blood cell (RBC) autoantibodies from patients with IgG warm-type autoimmune hemolytic anemia were labeled with iodine 125 and their RBC binding behavior characterized. Epitope-bearing RBC membrane polypeptides were identified after autoantibody immunoprecipitation of labeled membranes and immunoblotting. Immunoaffinity isolation of labeled membrane proteins with 12 different IgG hemolytic autoantibodies with protein A-agarose revealed a major polypeptide at Mr 95 to 110 kd, which coelectrophoresed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with a membrane component isolated with sheep IgG anti-band 3. Immunoprecipitation studies with chymotrypsinized RBCs resulted in the recovery of two labeled membrane polypeptides with molecular weights characteristically resulting from the chymotryptic fragmentation of band 3. Immunoblotting with sheep IgG anti-band 3 of the immunoprecipitated polypeptides confirmed that hemolytic autoantibody binding led to recovery of band 3 or its fragments. Two 125I-labeled IgG hemolytic autoantibodies showed binding behavior consistent with epitope localization on band 3. The labeled RBC autoantibodies bound immunospecifically to all types of human RBC tested, including those of rare Rh type (Rh-null, D--) at a site density of approximately 10(6) per RBC. The 125I-IgG in two labeled autoantibodies was 84% and 92% adsorbable by human and higher nonhuman primate RBCs. Antigen-negative animal RBC bound less than 10%, consistent with immunospecific RBC binding. IgG-1 was the major subclass in five autoantibodies tested; one of six fixed complement; and autoantibody IgG appeared polyclonal by isoelectric focusing. We conclude that IgG eluted from RBCs of patients with autoimmune hemolytic anemia consists predominantly of a single totally RBC-adsorbable antibody population that binds to antigenic determinants on band 3

  10. Concentration of circulating autoantibodies against HSP 60 is lowered through diving when compared to non-diving rats

    Directory of Open Access Journals (Sweden)

    Marianne B. Havnes

    2012-01-01

    Full Text Available Objective : Skin and ear infections, primarily caused by Pseudomonas aeruginosa (P. aeruginosa, are recurrent problems for saturation divers, whereas infections caused by P. aeruginosa are seldom observed in healthy people outside saturation chambers. Cystic fibrosis (CF patients suffer from pulmonary infections by P. aeruginosa, and it has been demonstrated that CF patients have high levels of autoantibodies against Heat shock protein 60 (HSP60 compared to controls, probably due to cross-reacting antibodies induced by P. aeruginosa. The present study investigated whether rats immunised with P. aeruginosa produced autoantibodies against their own HSP60 and whether diving influenced the level of circulating anti-HSP60 antibodies. Methods : A total of 24 rats were randomly assigned to one of three groups (‘immunised’, ‘dived’ and ‘immunised and dived’. The rats in group 1 and 3 were immunised with the bacteria P. aeruginosa, every other week. Groups 2 and 3 were exposed to simulated air dives to 400 kPa (4 ata with 45 min bottom time, every week for 7 weeks. Immediately after surfacing, the rats were anaesthetised and blood was collected from the saphenous vein. The amount of anti-HSP60 rat antibodies in the serum was analysed by enzyme linked immunosorbent assay. Results : The immunised rats (group 1 showed a significant increase in the level of autoantibodies against HSP60, whereas no autoantibodies were detected in the dived rats (group 2. The rats both immunised and dived (group 3 show no significant increase in circulating autoantibodies against HSP60. A possible explanation may be that HSP60 is expressed during diving and that cross-reacting antibodies are bound.

  11. Clinical and pathologic considerations of the qualitative and quantitative aspects of lupus nephritogenic autoantibodies: A comprehensive review.

    Science.gov (United States)

    Gatto, Mariele; Iaccarino, Luca; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2016-05-01

    Autoantibodies are key mediators in determining the clinical manifestations of systemic lupus erythematosus (SLE). The mechanisms by which antibodies may be harmful to self tissues encompass complement mediated inflammation, cell apoptosis and immune-complexes mediated damage, however the precise cooperation of antibodies in SLE have not been unravelled so far. Lupus nephritis (LN) is a protean feature of SLE resulting in wide variety of symptoms including asymptomatic proteinuria, mild renal disease until end-stage renal failure which are triggered by complex autoantibody interactions. Novel clues concerning development and self-maintenance of LN have come to light in recent times, pointing straight to a multistep inflammatory process which is incited by anti-chromatin antibodies, the best known being anti-DNA and anti-nucleosome antibodies, culminating in a self-maintaining inflammatory loop with spreading of glomerular inflammation. In the maintenance of the inflammatory process pro-inflammatory antibodies are involved, among which anti-C1q are thought to play a major role, whereas hindrance of the nephritic process could be actively mediated by protective autoantibodies. Despite being so relevant in occurrence of LN, nor anti-chromatin neither anti-C1q antibodies have been precisely characterized in terms of origin, antigen specificity and mechanisms of action. Moreover, novel autoantibodies are emerging in LN which can modify disease course, whereas the pathogenic value of a myriad of cross-reactive antibodies has been progressively challenged. The aim of this review is to give a comprehensive view of known and emerging autoantibody reactivities involved in renal inflammation and damage going over their origin, mechanisms of action and interactions in determining LN course. PMID:26879422

  12. A rabbit autoantibody specific for the 46-kDa form of 2',3'-cyclic nucleotide 3'-phosphodiesterase.

    Science.gov (United States)

    Möller, J R; Ramaswamy, S G; Jacobowitz, D M; Quarles, R H

    1992-05-01

    An autoantibody occurring in the serum of an apparently normal rabbit that immunocytochemically stains myelin sheaths and oligodendrocytes in rat brain was shown to react specifically with the 46-kDa isoform of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) (EC 3.1.4.37) in a number of species. Identification of the shorter isoform of the enzyme (CNP1) as the antigen was achieved by comparing the immunostaining of Western blots by the autoantibody with that of a well-characterized anti-CNP antiserum. The 46-kDa antigen reacting with the autoantibody exhibited the same Mr and pI as the small isoform of CNP on two-dimensional gels and showed a similar enrichment in purified CNS myelin. The autoantibody has very high affinity for CNP1 and is capable of detecting the very low amounts of this enzyme in peripheral nerve, spleen, adrenal gland, pancreas, testis, and intestine. Testing the reactivity of the autoantibody with synthetic peptides by enzyme-linked immunosorbent assay revealed that it reacted with the N-acetylated decapeptide corresponding to the N-terminus of CNP1, but did not react if the peptide was not acetylated or if the acetyl group was replaced with a palmityl group. The lack of reactivity with CNP2, which differs from CNP1 by a 20-amino acid extension at the N-terminus of the protein as a result of alternative splicing, may be due to the absence of the N-acetyl moiety that is part of the epitope and/or blocking of antibody binding to the decapeptide by extension of the polypeptide chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1373178

  13. Correlation between imaging findings and autoantibody levels and prognosis in patients with neuropsychiatric systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Objective: To investigate the correlation between cranial magnetic resonance imaging (MRI) findings and autoantibody levels in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), and to elucidate the role of MRI findings in predicting the prognosis of NPSLE. Methods: In total, 36 well-documented cases of NPSLE diagnosed definitely were selected. All the patients were divided into survival group (n=27) and dead group (n=9). Anti-nuclear antibodies and anti-dsDNA antibodies in serum were detected by indirect immunofluorescence and colloidal gold spot penetration method, respectively. Immunoblotting method was used to detect anti-Sm, anti-SSA, anti-SSB, anti U1-RNP, and anti-ribosomal P protein antibodies. Anti-cardiolipin antibody (ACL) was detected byELISA method. The correlation between MRI findings of cerebral lesions and autoantibodies, and prognosis was analyzed. Results: Cranial MRI scans on admission were abnormal in 32 patients (88.9% ), among which 21 cases showed diffuse manifestations, 10 cases showed focal lesion in brain and 1 case showed brain atrophy. The diffuse lesion on MRI showed multiple spotty or patchy normal intensity signal on T1-weighted image (T1WI) and high-intensity signal changes on T2-weighted image (T2WI). The focal lesion showed single spotty or patchy normal intensity signal on T1WI and high-intensity signal changes on T2WI. The lesion sites included basal ganglia, subcortical white matter, anterior and posterior horn of lateral ventricle, semiovale center, cerebral cortex, brainstem and cerebellum. Of 9 patients in dead group, 6 cases presented with focal lesion and the percentage of focal lesion cases in dead group was significantly higher than that in survival group (P<0.01). The percentages of lesion number in brainstem and basal ganglia in dead group were 11.5% and 26.9% , respectively, which were significantly higher than those in survival group (P<0.05 or P<0.01). The positive rate of ACL in cases with focal

  14. THE ROLE OF DISEASE STAGE, PLASMA VIRAL LOAD AND Tregs ON AUTO-ANTIBODY PRODUCTION IN THE SIV INFECTED NON-HUMAN PRIMATES1

    OpenAIRE

    Ansari, A; Pereira, Lara E.; Ann E Mayne; Onlamoon, Nattawat; Pattanapanyasat, Kovit; Mori, Kazuyasu; Villinger, F.

    2007-01-01

    Auto-antibodies appear in the sera of rhesus macaques following SIV infection. The present study was conducted to examine the role of viral load, anti-viral chemotherapy and stage of disease on the titers of such auto-antibodies and the spectrum of auto-antigens that become the target of such auto-immune responses. In addition, the role of regulatory T cells (Tregs) was also examined. Results of these studies showed that the highest auto-antibody titers were noted in animals with lower relati...

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

    DEFF Research Database (Denmark)

    Carle, A.; Laurberg, P.; Knudsen, N.; Perrild, H.; Ovesen, Lars; Rasmussen, Lone Banke; Jørgensen, T.; Pedersen, I.B.

    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...... 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...... against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb). Results: In spontaneously hypothyroid patients: > 99% were antibody-positive ( TPOAb or TgAb), TPOAb were more often measurable than TgAb (95.9 vs. 80.7%, p, <0.001). A statistically significant but modest correlation was observed between the...

  16. EUROPattern Suite technology for computer-aided immunofluorescence microscopy in autoantibody diagnostics.

    Science.gov (United States)

    Krause, C; Ens, K; Fechner, K; Voigt, J; Fraune, J; Rohwäder, E; Hahn, M; Danckwardt, M; Feirer, C; Barth, E; Martinetz, T; Stöcker, W

    2015-04-01

    Antinuclear autoantibodies (ANA) are highly informative biomarkers in autoimmune diagnostics. The increasing demand for effective test systems, however, has led to the development of a confusingly large variety of different platforms. One of them, the indirect immunofluorescence (IIF), is regarded as the common gold standard for ANA screening, as described in a position statement by the American College of Rheumatology in 2009. Technological solutions have been developed aimed at standardization and automation of IIF to overcome methodological limitations and subjective bias in IIF interpretation. In this review, we present the EUROPattern Suite, a system for computer-aided immunofluorescence microscopy (CAIFM) including automated acquisition of digital images and evaluation of IIF results. The system was originally designed for ANA diagnostics on human epithelial cells, but its applications have been extended with the latest system update version 1.5 to the analysis of antineutrophil cytoplasmic antibodies (ANCA) and anti-dsDNA antibodies. PMID:25801895

  17. Anti-ATP synthase autoantibodies from patients with Alzheimer's disease reduce extracellular HDL level.

    Science.gov (United States)

    Vacirca, Davide; Barbati, Cristiana; Scazzocchio, Beatrice; Masella, Roberta; Rosano, Giuseppe; Malorni, Walter; Ortona, Elena

    2011-01-01

    Aside from being an integral protein involved in the synthesis and hydrolysis of ATP, Ecto-F1-ATPase plays a role in cholesterol homeostasis. We demonstrated the presence of autoantibodies to ecto-F1-ATPase (ASabs) in sera and cerebrospinal fluids from patients with Alzheimer's disease (AD). Herein we show that ASabs, unlike irrelevant antibodies, can increase cellular uptake of HDL, a risk factor for the development of AD, via a mechanism involving the prototypical function of ecto-F1-ATPase: the generation of ADP due to the hydrolysis of ATP. Piceatannol, a specific inhibitor ecto-F1-ATPase, completely hindered these effects. We hypothesize that ASabs could exert a pathogenetic role in AD. PMID:21677380

  18. 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...

  19. Regulation of naturally occurring autoantibody secretion by a radiosensitive lymphocyte: initial characterization and ontogeny

    Energy Technology Data Exchange (ETDEWEB)

    Moticka, E.J.

    1983-10-01

    Low level irradiation (400-500 R) of normal mice or of murine spleen cells resulted in the detection of an enhanced number of plaque-forming cells against bromelain-treated autologous red cells (Br MRBC) 1 day later. The mechanism responsible for the increased numbers of plaques is apparently the elimination of a suppressor T cell since the addition of thymocytes or of Lyt 1+2+ splenic cells to cultures of irradiated cells reversed the radiation-induced increase. Studies on the ontogeny of the phenomenon indicate that anti-Br MRBC plaques can be formed by spleen cells taken from mice shortly after birth although adult levels are not reached until after 3 weeks of age. Radiation-induced increases in the number of plaques were not seen until 3 weeks of age, thus, suggesting a temporal developmental sequence of the ability to produce autoantibodies and to regulate such production.

  20. Staining pattern classification of antinuclear autoantibodies based on block segmentation in indirect immunofluorescence images.

    Directory of Open Access Journals (Sweden)

    Jiaqian Li

    Full Text Available 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%.

  1. Autoantibody profiling of benign and malignant thyroid tumors and design of a prototype diagnostic array

    Directory of Open Access Journals (Sweden)

    K V Lanshchakov

    2012-06-01

    Full Text Available Currently the “gold standard” in diagnostics of thyroid tumors is a fine-needle aspiration cytology (FNAC. However, FNAC cannot discriminate between benign and malignant thyroid tumors in 15 to 30% of observations. In order to develop an additional tool for differential diagnostics of thyroid tumors we evaluated the diagnostic performance of 3-antigen serum autoantibody signature in groups of benign ( n = 22 and malignant ( n = 26 thyroid tumors using a dot-blot ELISA-based analysis The sensitivity and specificity of resultant array were estimated to be 55–60% and 95–100%, respectively ( p < 0.001 according to one-sided Fisher Exact Test. Thus, we created a prototype antigen array for differential diagnostics of thyroid tumors which can be regarded as a platform for design of more complicated panel, highly sensitive in thyroid cancer detection, which can significantly improve the accuracy of preoperative diagnosis of thyroid cancer.

  2. Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo; Bahnsen, M; Dietrichson, O; Svejgaard, A

    1981-01-01

    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......) were significantly more prevalent in patients with cirrhosis than in sex- and age-matched controls. Antimitochondrial antibodies and liver cell membrane antibody were found in 4% of the patients, and in none of the controls, but this difference was not significant. Patients with HLA-B8 and/or HLA-B12...... had higher titres of ANA (n.s.) and SMA (P less than 0.05) than patients without these HLA antigens. Serum concentrations of testosterone were significantly lower in ANA-positive patients than in those negative (P less than 0.05), and a similar tendency was found in SMA-positive patients. With...

  3. Detection and identification of antinuclear autoantibodies in the serum of normal blood donors.

    Science.gov (United States)

    de Vlam, K; De Keyser, F; Verbruggen, G; Vandenbossche, M; Vanneuville, B; D'Haese, D; Veys, E M

    1993-01-01

    The occurrence of antinuclear antibodies (ANA) in the serum of 485 healthy volunteer blood donors was assessed. Sixty two sera displayed nuclear immunofluorescence staining on Hep-2 cells using a polyvalent anti-Ig conjugate. In general, the titer of these antibodies was low (42/62 sera displaying a titer lower than or equal to 1:80). In only 23 sera were the ANA of the IgG isotype, which is the more disease-related immunoglobulin class of autoantibodies. In order to define the frequency of antibodies to extractable nuclear antigens and dsDNA within this population, sera were further analyzed by counterimmunoelectrophoresis. Western blot and the Crithidia luciliae assay. One serum displayed weak antids DNA reactivity; another serum had anti-SSA/Ro activity. On Western blot several patterns were found. They could not be identified with any of the available reference antisera. PMID:8403584

  4. Recent advancement on autoantigens, autoantibodies and inflammatory cells in subepidermal autoimmune bullous diseases

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2007-01-01

    Subepidermal autoimmune bullous diseases (SABD) are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are discussed including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), cicatricial pemphigoid (CP), bullous systemic lupus erythematosus (BSLE), and Anti-p200 pemphigoid. Emphasis on recent advancement is presented. In recent years, improved Knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in some SABD. Defects of such structures cause the subepidermal bullous diseases and have also led to the discovery of new diseases (e.g. anti-p200-pemphigoid). Recent studies have outlined the important role of autoantibodies, mast cell lymphocytes and their cytokines in pathogenesis of SABD.

  5. Autoantibodies against constituents of nuclear pore complexes in patient with primary biliary cirrhosis and autoimmune hepatitis

    International Nuclear Information System (INIS)

    Sera obtained from patients with autoimmune liver disease were screened in indirect immunofluorescence microscopy for the presence of autoantibodies. Patients' sera, which strongly stained nuclei (ANA) with peripheral accentuation, were used for further experiments to define the corresponding antigen(s). Nuclei and nuclear subfractions were isolated from HeLaS3 cells and used as antigen source. Immunoblotting experiments were performed after separation of nuclear proteins by one- and two-dimensional polycrystalamide gel electrophoresis. Some ANA positive sera recognized the nuclear protein with molecular mass of approximately 200 kDa. Further analysis revealed that the patients' sera reacted with gp210, an integral protein of the nuclear pores. The incidence and clinical significance of these antibodies is discussed. (author). 9 refs, 4 figs

  6. Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice.

    Science.gov (United States)

    Gilmer, John; Serve, Kinta; Davis, Chad; Anthony, Marti; Hanson, Robert; Harding, Tanner; Pfau, Jean C

    2016-06-01

    Libby amphibole (LA) causes a unique progressive lamellar pleural fibrosis (LPF) that is associated with pulmonary function decline. Pleural fibrosis among the LA-exposed population of Libby, MT, has been associated with the production of anti-mesothelial cell autoantibodies (MCAA), which induce collagen production from cultured human mesothelial cells. We hypothesized that the progressive nature of LPF could be at least partially attributed to an autoimmune process and sought to demonstrate that LA-induced MCAA trigger collagen deposition in vivo. C57BL/6 mice were exposed to LA for 7 mo, and serum was tested for MCAA by cell-based ELISA on primary mouse mesothelial cells. When treated in vitro with serum from mice exposed to LA, mesothelial cells upregulated collagen matrix production. This effect was lost when the serum was cleared of IgG using protein G beads, implicating IgG autoantibodies. Using the peritoneal cavity as a surrogate for the pleural cavity, groups of naïve (non-asbestos-exposed) mice were injected intraperitoneally with 1) control serum, 2) one dose of serum from LA-exposed mice (LA serum), 3) two doses of LA serum, or 4) two doses of LA serum cleared of IgG. After 1 mo, analysis of collagen in peritoneal walls using two-photon confocal microscopy (SHG analysis) and a hydroxyproline assay demonstrated significant increases in collagen by LA serum but not control or cleared serum. These data support the hypothesis that MCAA in LA-exposed mice induce fibrotic responses in vivo, demonstrating that an autoimmune component may be contributing to the progressive pleural fibrosis seen in LA-exposed patients. PMID:27106292

  7. No evidence of circulating autoantibodies against osteoprotegerin in patients with celiac disease

    Institute of Scientific and Technical Information of China (English)

    Tiziana Larussa; Evelina Suraci; Immacolata Nazionale; Isabella Leone; Tiziana Montalcini; Ludovico Abenavoli; Maria Imeneo

    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.

  8. Serum thyroid autoantibodies in patients with idiopathic either acute or chronic urticaria.

    Science.gov (United States)

    Gangemi, S; Saitta, S; Lombardo, G; Patafi, M; Benvenga, S

    2009-02-01

    In Italy, only one study was conducted on the detection of serum thyroid autoantibodies (ATA) in patients with urticaria. This northern-Italy study reported a 23% rate of ATA positiveness in 52 patients with chronic idiopathic urticaria (CIU). During the years 1998-2006, 688 patients with urticaria were hospitalized at our Division of Allergy and Clinical Immunology. Thyroglobulin and thyroperoxidase autoantibodies (TgAb and TPOAb) were assayed at admission in 144/688 patients. Of the 144 patients (mean age: 42.3+/-15.8 yr, range 17-84), 95 (72 women and 23 men) had an history of CIU (CIU group) and 49 (44 women and 5 men) did not [acute urticaria group or (AU)]. Of the 144 patients, 37 (25.7%) tested positive for at least one ATA: 31 with CIU (32.6%) and 6 with AU (12.2%, chi2=7.037, p=0.008). Positiveness for TPOAb or TgAb was 30/37 (81.1%) or 17/37 (45.9%); 10/37 (27.0%). Pre-hospitalization duration of CIU was longer in the 31 ATA positive patients compared to the 64 ATA negative patients (207.2+/-273.4 vs 81.6+/-106.3 weeks, p=0.015). Pre-hospitalization duration of CIU correlated positively with the log10-transformed serum concentration of TPOAb in the 25 CIU patients who tested TPOAb positive (r=0.42, p=0.039). We conclude that our rate of 31/95 (32.6%) positiveness for at least one type of ATA in CIU is greater than that of 6 representative international studies published between the years 2000 and 2006 (111/488 or 22.7%, range 15-29%, chi2=4.884, p=0.027). PMID:19411805

  9. Autoantibodies against glutamate receptor δ2 after allogenic stem cell transplantation

    Science.gov (United States)

    Miske, Ramona; Hahn, Stefanie; Rosenkranz, Thorsten; Müller, Matthias; Dettmann, Inga M.; Mindorf, Swantje; Denno, Yvonne; Brakopp, Stefanie; Scharf, Madeleine; Teegen, Bianca; Probst, Christian; Melzer, Nico; Meinck, Hans-Michael; Terborg, Christoph; Stöcker, Winfried

    2016-01-01

    Objective: To report on a Caucasian patient who developed steroid-responsive transverse myelitis, graft vs host disease of the gut, and anti-GluRδ2 after allogenic stem cell transplantation. Methods: Histoimmunoprecipitation (HIP) with the patient's serum and cryosections of rat and porcine cerebellum followed by mass spectrometry was used to identify the autoantigen. Correct identification was verified by indirect immunofluorescence using recombinant GluRδ2 expressed in HEK293 cells. Results: The patient's serum produced a granular staining of the cerebellar molecular layer (immunoglobulin G1 and immunoglobulin G3; endpoint titer: 1:1,000) but did not react with other CNS tissues or 28 established recombinant neural autoantigens. HIP revealed a unique protein band at ∼110 kDa that was identified as GluRδ2. The patient's serum also stained GluRδ2 transfected but not mock-transfected HEK293 cells. Control sera from 38 patients with multiple sclerosis, 85 patients with other neural autoantibodies, and 205 healthy blood donors were negative for anti-GluRδ2. Preadsorption with lysate from HEK293-GluRδ2 neutralized the patient's tissue reaction whereas control lysate had no effect. In addition to anti-GluRδ2, the patient's serum contained immunoglobulin G autoantibodies against the pancreatic glycoprotein CUZD1, which are known to be markers of Crohn disease. Conclusions: In the present case, the development of anti-GluRδ2 was associated with transverse myelitis, which was supposedly triggered by the stem cell transplantation. Similar to encephalitis in conjunction with anti-GluRδ2 reported in a few Japanese patients, the patient's neurologic symptoms ameliorated after steroid therapy. PMID:27458598

  10. Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Pan, Qingjun; Guo, Linjie; Wu, Jing; Cai, Jun; Liao, Huanjin; Lan, Qiaofen; Peng, Yanxia; He, Yiming; Liu, Hua-Feng

    2016-01-01

    In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P < 0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r = 0.61, P < 0.05; r = 0.40, P < 0.05; and r = 0.54, P < 0.05, resp.) and negatively correlated with 24-hour urinary protein (r = 0.49, P < 0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P < 0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r = 0.34, P < 0.05; r = 0.51, P < 0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE. PMID:27597802

  11. Immunocapture and Identification of Cell Membrane Protein Antigenic Targets of Serum Autoantibodies*

    Science.gov (United States)

    Littleton, Edward; Dreger, Mathias; Palace, Jackie; Vincent, Angela

    2009-01-01

    There is increasing interest in the role of antibodies targeting specific membrane proteins in neurological and other diseases. The target(s) of these pathogenic antibodies is known in a few diseases, usually when candidate cell surface proteins have been tested. Approaches for identifying new antigens have mainly resulted in the identification of antibodies to intracellular proteins, which are often very useful as diagnostic markers for disease but unlikely to be directly involved in disease pathogenesis because they are not accessible to circulating antibodies. To identify cell surface antigens, we developed a “conformational membrane antigen isolation and identification” strategy. First, a cell line is identified that reacts with patient sera but not with control sera. Second, intact cells are exposed to sera to allow the binding of presumptive autoantibodies to their cell surface targets. After washing off non-bound serum components, the cells are lysed, and immune complexes are precipitated. Third, the bound surface antigen is identified by mass spectrometry. As a model system we used a muscle cell line, TE671, that endogenously expresses muscle-specific tyrosine receptor kinase (MuSK) and sera or plasmas from patients with a subtype of the autoimmune disease myasthenia gravis in which patients have autoantibodies against MuSK. MuSK was robustly detected as the only membrane protein in immunoprecipitates from all three patient samples tested and not from the three MuSK antibody-negative control samples processed in parallel. Of note, however, there were many intracellular proteins found in the immunoprecipitates from both patients and controls, suggesting that these were nonspecifically immunoprecipitated from cell extracts. The conformational membrane antigen isolation and identification technique should be of value for the detection of highly relevant antigenic targets in the growing number of suspected antibody-mediated autoimmune disorders. The

  12. Autoantibody-Mediated Pulmonary Alveolar Proteinosis in Rasgrp1-Deficient Mice.

    Science.gov (United States)

    Ferretti, Andrew; Fortwendel, Jarrod R; Gebb, Sarah A; Barrington, Robert A

    2016-07-15

    Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome caused by the accumulation of surfactants in the alveoli. The most prevalent clinical form of PAP is autoimmune PAP (aPAP) whereby IgG autoantibodies neutralize GM-CSF. GM-CSF is a pleiotropic cytokine that promotes the differentiation, survival, and activation of alveolar macrophages, the cells responsible for surfactant degradation. IgG-mediated neutralization of GM-CSF thereby inhibits alveolar macrophage homeostasis and function, leading to surfactant accumulation and innate immunodeficiency. Importantly, there are no rodent models for this disease; therefore, underlying immune mechanisms regulating GM-CSF-specific IgG in aPAP are not well understood. In this article, we identify that autoimmune-prone Rasgrp1-deficient mice develop aPAP: 1) Rasgrp1-deficient mice exhibit reduced pulmonary compliance and lung histopathology characteristic of PAP; 2) alveolar macrophages from Rasgrp1-deficient mice are enlarged and exhibit reduced surfactant degradation; 3) the concentration of GM-CSF-specific IgG is elevated in both serum and bronchoalveolar lavage fluid from Rasgrp1-deficient mice; 4) GM-CSF-specific IgG is capable of neutralizing GM-CSF bioactivity; and 5) Rasgrp1-deficient mice also lacking CD275/ICOSL, a molecule necessary for conventional T cell-dependent Ab production, have reduced GM-CSF-specific autoantibody and do not develop PAP. Collectively, these studies reveal that Rasgrp1-deficient mice, to our knowledge, represent the first rodent model for aPAP. PMID:27279372

  13. Proinflammatory Cytokines and Antiskin Autoantibodies in Patients With Inherited Epidermolysis Bullosa.

    Science.gov (United States)

    Annicchiarico, Giuseppina; Morgese, Maria Grazia; Esposito, Susanna; Lopalco, Giuseppe; Lattarulo, Michele; Tampoia, Marilina; Bonamonte, Domenico; Brunetti, Luigia; Vitale, Antonio; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo

    2015-10-01

    Epidermolysis bullosa (EB) is a rare disorder characterized by inherited skin adhesion defects with abnormal disruption of the epidermal-dermal junction in response to mechanical trauma. Our aim was to investigate a set of cytokine levels in serum samples from patients suffering from epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), and healthy controls (HCs), exploring their potential correlations with antiskin autoantibody titers and disease activity. Forty patients afferent to the Dermatological Ward of Bari City Hospital and 9 HCs were enrolled and subdivided according to the dystrophic (DEB) and simplex forms (EBS). We found a significant increase in interleukin (IL)-1β plasmatic levels of DEB (P = 0.0224) and EBS (P = 0.0465) patients compared to HCs; IL-6 levels were significantly higher in DEB than in EBS patients (P = 0.0004) or HCs (P = 0.0474); IL-2 levels were significantly increased in DEB compared with EBS (P = 0.0428). Plasmatic tumor necrosis factor-β and interferon-γ were higher in DEB patients than in HCs (P = 0.0448 and 0.0229). Conversely, tumor necrosis factor-α was significantly decreased in DEB (P = 0.0034). IL-5 correlated with anti-BP180 (r = -0.5018, P = 0.0338), anti-BP230 (r = -0.6097, P = 0.0122), and anticollagen VII (r = -0.5166, P = 0.0405) autoantibodies; interferon-γ correlated with anti-BP180 (r = 0.9633, P systemic inflammatory disease rather than a skin-limited disorder; clinical disease activity scores could be also integrated by laboratory data such as IL-6 and IL-12 dosage; biotherapies targeting specific cytokine networks probably represent a way to go in the future. PMID:26496255

  14. Post-streptococcal auto-antibodies inhibit protein disulfide isomerase and are associated with insulin resistance.

    Directory of Open Access Journals (Sweden)

    Adi Aran

    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.

  15. Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Stinton Laura M

    2003-09-01

    Full Text Available Abstract Background Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. Methods Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL were detected by ELISA. Results Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. Conclusion This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.

  16. Auto-antibodies to vascular endothelial cadherin in humans: association with autoimmune diseases.

    Science.gov (United States)

    Bouillet, L; Baudet, A E; Deroux, A; Sidibé, A; Dumestre-Perard, C; Mannic, T; Treillard, B; Arboleas, M A; Chiquet, C A; Gulino-Debrac, D G; Vilgrain, I Y

    2013-11-01

    To identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors (n=75). Sera from patients (n=100) with various autoimmune diseases, including rheumatoid arthritis (n=23), systemic lupus erythematosus (SLE, n=31), systemic sclerosis (n=30), and Behçet's disease (BD, n=16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis (PPP<0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the early pathogenicity of these

  17. The Clinical Significance of Autoantibodies in Hepatitis C Patients Submitted to Interferon Treatment

    Directory of Open Access Journals (Sweden)

    Eduardo Rodrigues-Pinto

    2015-01-01

    Full Text Available Hepatitis C virus is associated with several immune-mediated phenomena, presented usually as extra-hepatic hepatitis C manifestations. A predisposition to autoimmunity associated with the presence of baseline autoantibodies has been demonstrated in interferon mediated autoimmune diseases. We report a male patient, 34 years old, with genotype 1, chronic hepatitis C (hepatitis C viremia 1.432.463 UI/mL and family history of psoriasis. He had high levels of transaminases and immunology showed positive antinuclear antibodies (1/320 and anti-smooth-muscle antibodies, with elevated immunoglobulin G (1740 mg/dL. Liver biopsy revealed a F1/2 Metavir score, histologic activity index of 3 and mild piecemeal necrosis. Antiviral treatment was started with peg-interferon α2a 180 mcg plus ribavirin 1200 mg, and the patient had rapid virologic response, normalization of transaminases, negativation of antinuclear antibodies positivity and decrease of immunoglobulin levels. However, at week 22, he developed psoriatic-like eczema and arthritis with functional limitation. Due to suspicion of latent psoriatic arthritis not previously diagnosed, he was started on methotrexate 10 mg/weekly with improvement of psoriatic plaques, arthritis and functional limitation. Patient achieved sustained virologic response, with normal transaminases and no significant changes in immunology. Post-treatment median hepatic elastography was 3.6 kPa. Autoimmunity in hepatitis C infection is not limited to surrogate autoantibody seropositivity, but may embrace the full spectrum of autoimmune disorders.

  18. Autoantibodies against protective molecules-C1q, C-reactive protein, serum amyloid P, mannose-binding lectin, and apolipoprotein A1 - Prevalence in systemic lupus erythematosus

    NARCIS (Netherlands)

    Shoenfeld, Yehuda; Szyper-Kravitz, Martine; Witte, Torsten; Doria, Andrea; Tsutsumi, Akito; Tatsuya, Abe; Dayer, Jean-Michel; Roux-Lombard, Pascale; Fontao, Lionel; Kallenberg, Cees G. M.; Bijl, Marc; Matthias, Torsten; Fraser, Abigail; Zandman-Goddard, Gisele; Blank, Miri; Gilburd, Boris; Meroni, Pier Luigi; Shoenfeld, Y; Gershwin, ME

    2007-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of several autoantibodies. Among the multiple factors involved in SLE development, apoptotic defects and impaired clearance of cellular debris have gained considerable interest, as they contribute to autoanti

  19. Single Nucleotide Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphisms in Antiislet Autoantibody-Negative Patients at Onset of Diabetes

    OpenAIRE

    Yu, Jeesuk; Steck, Andrea K.; Babu, Sunanda; Yu, Liping; Miao, Dongmei; McFann, Kim; Hutton, John; Eisenbarth, George S.; Klingensmith, Georgeanna

    2008-01-01

    Context: There is controversy as to whether type 2 diabetes genetic susceptibility contributes to type 1 diabetes, and it is not known what proportion of islet autoantibody-negative new onset subjects have type 2 diabetes risk alleles.

  20. 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

  1. 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.

  2. Protamine-containing insulins are strong risk factors, and human insulin analogues are possible risk factors for insulin autoantibody: case-control study

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kinoshita

    2013-01-01

    Full Text Available Insulin autoantibody is known to cause fluctuation of blood glucose. We examined whether medications for diabetes are risk factors for insulin autoantibody. Especially, we examined the associations between types of insulin and insulin autoantibody. We performed a case-control study. From April 2005 to March 2010, insulin autoantibody was measured 273 times in 217 patients in our hospital. Insulin autoantibody was positive (greater than 10% 53 times in 19 patients (case, and was negative 220 times in 198 patients (control. Oral hypoglycemic agents were not risk factors for insulin autoantibody; the odds ratio was 0.0. In contrast, insulin use was a significant risk factor for insulin autoantibody; the odds ratio (95% confidence interval was 56.3 (7.3-432.5. As for the types of insulin and insulin autoantibody, human insulins without protamine were not risk factors; the odds ratio was 0.0. For protamine-containing insulins, the odds ratio and adjusted odds ratio (adjusted by age, gender, and disease: type 1 diabetes mellitus, type 2 diabetes mellitus, and no diabetes were 35.3 (9.6-129.5 and 29.6 (7.6- 115.4, respectively. For Aspart-containing insulins, they were 6.2 (2.2-17.9 and 3.8 (1.2- 12.0, respectively. For Glargine, they were 3.2 (0.6-16.7 and 1.3 (0.2-8.3, respectively. To decrease the problem of insulin antibody, avoiding the use of protamine-containing insulins and avoiding the use of human insulin analogues might be preferable for the patients with diabetes.

  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.......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. The detection of canine autoantibodies to thyroid antigens by enzyme-linked immunosorbent assay, hemagglutination and indirect immunofluorescence.

    OpenAIRE

    Haines, D M; Lording, P M; Penhale, W. J.

    1984-01-01

    Autoantibodies to thyroid antigens in serums from 34 clinically hypothyroid dogs were detected by various methods. Antibodies to thyroglobulin were detectable by enzyme-linked immunosorbent assay (ELISA) in 59%, by chromic chloride hemagglutination in 53% and by indirect immunofluorescence on formalin-fixed, paraffin-embedded, trypsin-digested thyroid tissue in 73% of samples. Antibody to thyroid microsomal antigen was detectable by ELISA in 29% of serums. Indirect immunofluorescence showed c...

  5. Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies

    OpenAIRE

    Michael Mahler; Pier-Luigi Meroni; Xavier Bossuyt; 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...

  6. Interference of anti-T3 autoantibodies in the measurement of total and free T3 in serum

    OpenAIRE

    Abraham, Rebecca; Chawla, R

    1997-01-01

    A case of anti-trilodothyronine autoantibodies is presented in this report. The thyroid hormone profile of a hypertensive patient, with multinodular goiter and history of exogenous thyroid hormone therapy, was found to be highly ambiguous. The total as well as free T3 levels were consistently high (out of range) whereas the T4 (total and free) values were always within normal limits. The thyrotropin was found to be partially suppressed. Very low T3-Uptake indicated some kind of interference i...

  7. Anti-FcepsilonRIalpha autoantibodies in autoimmune-mediated disorders. Identification of a structure-function relationship.

    OpenAIRE

    Fiebiger, E; Hammerschmid, F.; Stingl, G; Maurer, D

    1998-01-01

    Anti-FcepsilonRIalpha autoantibodies (autoAbs) occur and may be of pathogenetic relevance in a subset of chronic urticaria (CU) patients. To analyze the prevalence and magnitude of the humoral anti-FcepsilonRIalpha response in cohorts of CU patients compared with individuals suffering from classic skin- related (auto)immune diseases, we developed an ELISA system for the measurement of anti-FcepsilonRIalpha autoAbs in nonfractionated serum samples. Results obtained using this assay correlated ...

  8. Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study

    OpenAIRE

    2015-01-01

    The clinical utility of the functional TSH receptor autoantibodies was prospectively evaluated in patients with thyroid-associated orbitopathy (TAO). Ophthalmic, endocrine, and serological investigations were performed in 101 consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb) and blocking (TBAb) antibody levels were measured with two bioassays using cells that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results are expressed as percentage ...

  9. Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

    OpenAIRE

    Vorobyev, Artem; Ujiie, Hideyuki; Recke, Andreas; Buijsrogge, Jacqueline J. A.; Jonkman, Marcel F.; Pas, Hendrikus; Iwata, Hiroaki; HASHIMOTO, TAKASHI; Kim, Soo-Chan; Kim, Jong Hoon; Groves, Richard; Samavedam, Unni; Gupta, Yask; Schmidt, Enno; Zillikens, Detlef

    2015-01-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease of the skin and mucous membranes, characterized by autoantibodies against type VII collagen (COL7), a major component of anchoring fibrils. Different clinical EBA phenotypes are described, including mechanobullous and inflammatory variants. Most EBA patients' sera react with epitopes located within the non-collagenous 1 (NC1) domain of human COL7. However, it has remained unclear whether antibody binding to these differ...

  10. Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays.

    Science.gov (United States)

    Crane, Jonathan M; Lam, Chiwah; Rossi, Andrea; Gupta, Tripta; Bennett, Jeffrey L; Verkman, A S

    2011-05-01

    Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-rAb), together with a C terminus anti-AQP4 antibody. NMO-rAb titrations showed binding with dissociation constants down to 44 ± 7 nm. Different NMO-rAbs and NMO patient sera showed a wide variation in NMO-IgG binding to M1 versus M23 AQP4. Differences in binding affinity rather than stoichiometry accounted for M1 versus M23 binding specificity, with consistently greater affinity of NMO-IgG binding to M23 than M1 AQP4. Binding and OAP measurements in cells expressing different M1:M23 ratios or AQP4 mutants indicated that the differential binding of NMO-IgG to M1 versus M23 was due to OAP assembly rather than to differences in the M1 versus M23 N termini. Purified Fab fragments of NMO-IgG showed similar patterns of AQP4 isoform binding, indicating that structural changes in the AQP4 epitope upon array assembly, and not bivalent cross-linking of whole IgG, result in the greater binding affinity to OAPs. Our study establishes a quantitative assay of NMO-IgG binding to AQP4 and indicates remarkable, OAP-dependent heterogeneity in NMO autoantibody binding specificity. PMID:21454592

  11. Reduced serum levels of autoantibodies against monomeric C-reactive protein (CRP) in patients with acute coronary syndrome

    OpenAIRE

    Wetterö, Jonas; Nilsson, Lennart; Jonasson, Lena; Sjöwall, Christoffer

    2009-01-01

    Introduction: Inflammation is pivotal in atherosclerosis. Minor C-reactive protein (CRP) response reflects low-grade vascular inflammation and the high-sensitivity CRP test with levels >= 3.0 mg/l predicts coronary vascular events and survival in angina pectoris as well as in healthy subjects. We and others recently reported autoantibodies against monomeric CRP (anti-CRP) in rheumatic conditions, e.g. systemic lupus erythematosus (SLE), and a connection between anti-CRP and cardiovascular ...

  12. Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies

    Science.gov (United States)

    Goette, Nora P.; Glembotsky, Ana C.; Lev, Paola R.; Grodzielski, Matías; Contrufo, Geraldine; Pierdominici, Marta S.; Espasandin, Yesica R.; Riveros, Dardo; García, Alejandro J.; Molinas, Felisa C.; Heller, Paula G.

    2016-01-01

    Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon. PMID:27494140

  13. Autoantibodies to protein transport and messenger RNA processing pathways: endosomes, lysosomes, Golgi complex, proteasomes, assemblyosomes, exosomes, and GW bodies.

    Science.gov (United States)

    Stinton, Laura M; Eystathioy, Theophany; Selak, Sanja; Chan, Edward K L; Fritzler, Marvin J

    2004-01-01

    Over 50 years ago the lupus erythematosus (LE) cell phenomenon was described and this was quickly followed by the introduction of the LE cell test and indirect immunofluorescence (IIF) to detect antinuclear antibodies (ANA) in clinical laboratories. Recently, attention has turned to the identification of the autoantigens that bind to cytoplasmic organelles such as the Golgi complex, endosomes and other "cytoplasmic somes". Three endosome autoantigens include early endosome antigen 1 (EEA1, 160 kDa), cytoplasmic linker protein-170 (CLIP-170, 170 kDa), and lysobisphosphatidic acid (LBPA). Antibodies to EEA1 were seen in a variety of conditions but approximately 40% of the patients had a neurological disease. Despite the prominence of lysosomes in cells and tissues, reports of autoantibodies are limited to the lysosomal antigen h-LAMP-2 and the cytoplasmic antineutrophil antibodies (cANCA). Autoantigens in the Golgi complex include giantin/macrogolgin, golgin-245, golgin 160, golgin-97, golgin 95/gm130, and golgin-67. More recently, there has been an interest in autoantibodies that bind components of the "SMN complex" or the "assemblyosome". Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. More recently, components of a novel cytoplasmic structure named GW bodies (GWBs) have been identified as targets of human autoantibodies. Components of GWBs include GW182, a unique mRNA-binding protein, like Sm proteins (LSms), and decapping (hDcp1) and exonuclease (Xrn) enzymes. Current evidence suggests that GWBs are involved in the cytoplasmic processing of mRNAs. Autoantibodies to the "cytoplasmic somes" are relatively uncommon and serological tests to detect most of them are not widely available. PMID:14962794

  14. Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo

    OpenAIRE

    Németh, Tamás; Futosi, Krisztina; Sitaru, Cassian; Ruland, Jürgen; Mócsai, Attila

    2016-01-01

    Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and derm...

  15. Complete elimination of cardiodepressant IgG3 autoantibodies by immunoadsorption in patients with severe heart failure

    International Nuclear Information System (INIS)

    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)

  16. Saffold Virus, a Human Cardiovirus, and Risk of Persistent Islet Autoantibodies in the Longitudinal Birth Cohort Study MIDIA.

    Directory of Open Access Journals (Sweden)

    German Tapia

    Full Text Available The aim of this study was to describe the frequency and distribution of Saffold virus in longitudinal stool samples from children, and test for association with development of persistent autoantibodies predictive of type 1 diabetes. A cohort of Norwegian children carrying the HLA genotype associated with highest risk of type 1 diabetes ("DR4-DQ8/DR3-DQ2" was followed with monthly stool samples from 3 to 35 months of age. Blood samples were tested for autoantibodies to insulin, glutamic acid decarboxylase65 and Islet Antigen-2. 2077 stool samples from 27 children with ≥ 2 repeatedly positive islet autoantibodies (cases, and 53 matched controls were analysed for Saffold virus genomic RNA by semi-quantitative real-time reverse transcriptase PCR. Saffold virus was found in 53 of 2077 (2.6% samples, with similar proportions between cases (2.5% and controls (2.6%. The probability of being infected by 3 years of age was 28% (95% CI 0.18-0.40. Viral quantities ranged from <1 to almost 105 copies/μl. Estimated odds ratio between islet autoimmunity and infection episodes prior to seroconversion was 1.98 (95% CI: 0.57-6.91, p = 0.29. Saffold virus had no statistically significant association with islet autoimmunity.

  17. Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis

    International Nuclear Information System (INIS)

    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

  18. Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Tanay, A.; Strober, S.; Logue, G.L.; Schiffman, G.

    1984-02-01

    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.

  19. 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.

  20. 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

  1. Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

    International Nuclear Information System (INIS)

    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 TH17 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 from

  2. 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.

  3. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus.

    Science.gov (United States)

    Ho, Roger C; Thiaghu, C; Ong, Huiyi; Lu, Yanxia; Ho, Cyrus S; Tam, Wilson W; Zhang, Melvyn W

    2016-02-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating presentations of SLE and comprises of psychiatric, central and peripheral neurological signs and symptoms. Previous studies suggest the possible associations between various autoantibodies (Abs) and NPSLE. The magnitudes of such association varied between studies. We performed a meta-analysis to pool data on serum and cerebrospinal fluid (CSF) levels and positivity of Abs in blood and cerebrospinal fluid in patients with NPSLE and SLE. A systematic literature search was conducted to identify studies that fulfilled inclusion criteria. A random-effects model was used to calculate overall combined odd ratio (OR) and mean levels with its corresponding 95% confidence interval to evaluate the relationship between individual Abs and NPSLE patients relative to SLE patients. Forty-one studies met the inclusion criteria and were used in this analysis. There was a significantly greater proportion of NPSLE patients who demonstrated positivity for serum anti-cardiolipin (aCL) Abs (OR=1.63, p=0.016), lupus anticoagulants (LA) Abs (OR=1.91 p=0.01), anti-phospholipid (APL) Abs (OR=2.08, p=0.001), anti-ribosomal P Abs (OR=2.29, pAbs (OR=9.50, pAbs (OR=36.84, p=0.001) as compared to SLE patients. Among the 19 neuropsychiatric syndromes, the positivity of these serum autoantibodies were found specifically significantly associated with the manifestations of mood disorder, psychosis, cerebrovascular disease, seizure disorders, acute confusional state, cognitive dysfunction, headache, movement disorder, demyelinating syndrome and polyneuropathy, with ORs ranging from 1.84 to 4.73. Meta-regression identified proportion of women as significant moderator for the heterogeneity of aCL (p=0.004) and anti-neuronal Abs (p=0.0007); mean age for the heterogeneity of aCL (p=0.042) and LA (p=0.020) Abs, mean duration of illness for the heterogeneity of aCL Abs (p=0.035), and mean SLEDAI scores for the heterogeneity

  4. 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

  5. Association of Immunofluorescence pattern of Antinuclear Antibody with Specific Autoantibodies in the Bangladeshi Population.

    Science.gov (United States)

    Sharmin, S; Ahmed, S; Abu Saleh, A; Rahman, F; Choudhury, M R; Hassan, M M

    2014-08-01

    Antinuclear antibody (ANA) is useful in the diagnosis of connective tissue disorder (CTD). Association of specific autoantibodies with the immunofluorescence pattern of ANA in CTD, noted in western literature has been considered as reference in all over the world. However, in Bangladesh no such research work or data correlating the autoantibodies and their ANA patterns is found. Objective of the study was 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 CTD patients. Serum samples of 152 CTD patients (Systemic lupus erythematosus, Rhumatoid arthritis, Sjogren's syndrome, Systemic sclerosis, Polymyositis, Mixed connective tissue disease) were diagnosed clinically, attending at Bangabandhu Sheikh Mujib Medical University (BSMMU) during the study period of January, 2010 to December, 2010. Samples were subjected for ANA testing by Indirect Immunofluorescence (IIF) on HEp-2 cell (ALPHADIA) in dilution of 1:40, 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, anti-SSB/La, anti-Scl-70 and anti-Jo-1. Out of 152 patients 110 (72.3%) cases were ANA positive by IIF on HEp-2 cell. ANA positive sera exhibited four fluorescence patterns such as speckled (50.8%), peripheral (21.6%) , homogenous (18.1%) and nucleolar pattern (9%). Peripheral pattern and homogenous pattern was predominantly associated with anti-dsDNA (p RNP (25.7%) then anti-Scl-70 (20%), anti-SSA (14.2%) and anti-SSB (5.7%). Multiple anti-ENA reactivities were identified in 34.28% cases. Peripheral and homogenous pattern is strongly associated with anti-dsDNA and speckled pattern may predict anti-ENA (specially ribonucleoprotiens). As a definite correlation between the ANA patterns and the group of antibodies was detected by dot immunoblot

  6. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    International Nuclear Information System (INIS)

    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

  7. Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children.

    Science.gov (United States)

    Wahlberg, Jeanette; Vaarala, Outi; Ludvigsson, Johnny

    2011-11-01

    A dominance of Th2 cytokine pattern is associated with allergic diseases, whereas a Th1 pattern has been reported in autoimmune type 1 diabetes (T1D). The Th1/Th2 paradigm has led to the interest in the relationship between these diseases. To investigate the association between atopic diseases, asthma and occurrence of T1D-related β-cell autoantibodies in children, we studied 7208 unselected 2.5-yr-old children from the All Babies in Southeast Sweden (ABIS) cohort. The ABIS cohort includes 17 055 (78.3% out of all 21 700) children born from October 1997 to October 1999, and followed prospectively with regular biological samples and questionnaires, at birth, at 1 and 2.5 yr. Risk factors for development of β-cell autoantibodies at the age of 2.5 yr were type of domiciliary, domestic animals (cat and dog) and getting a new brother/sister during first year of life. Maternal smoking during pregnancy [odds ratio (OR) 1.6] and heavy smoking at home (>10 vs. ≤10 cigarettes) implied risk for tyrosine phosphatase autoantibodies (IA-2A) (OR 2.9). Wheezing during the first year of life implied risk for glutamic acid decarboxylase autoantibodies (GADA) (OR 1.9) and double positivity for GADA and IA-2A (OR 9.1). Rash on several locations (at least three times during 12 months) (OR 1.7) as well as allergic symptoms related to fur-bearing animals (OR 2.7) implied risk for IA-2A. Food allergy against egg, cow-milk, fish, nuts/almonds (one or in combination) implied risk for GADA and IA-2A (OR 4.5). In a regression model wheezing during first year of life remained as a risk factor for GADA [OR 2.0, confidence interval (CI) 1.1-3.8; p = 0.031] and both GADA and IA-2A (OR 10.7, CI 3.9-29.4; p = 0.000). We conclude that allergic symptoms are associated with the development of T1D-related autoantibodies during the first years of life. PMID:21466648

  8. Amplified ELISA to detect autoantibodies to N-glycolyl-GM3 ganglioside.

    Science.gov (United States)

    Iznaga, N; Carr, A; Fernández, L E; Solozabal, J; Núñez, G; Perdomo, Y; Morales, A

    1996-01-01

    Numerous immunochemical methods are now available for the detection of antibodies to gangliosides. An amplified ELISA method for detection of autoantibodies to NGcGM3 ganglioside in the sera of patients with various type of renal diseases was developed. IgM antibodies were found in 39 out of 53 sera of patients using 30 normal healthy blood donor as a negative control. For human IgG conjugate no reactivity to NGcGM3 was seen in the sera. Positive ELISA results were confirmed by TLC-immunostaining using GM3, NGcGM3, NGcGM2 and Standard bovine gangliosides (GM1, GD1a, GD1b and GT1b). All sera were also assayed for reactivity with GM3 in ELISA to determine the line specificity of these antibodies. Based on these results, a protocol for a sensitive and reproducible amplification ELISA system for serum anti-NGcGM3 antibodies in patients with renal or other diseases is presented. The ELISA method described here in appear to be useful adjunt to measure antiNGcGM3 antibodies in sera of patients with various type of renal or other diseases. PMID:16296265

  9. Peptides Targeting the Desmoglein 3 Adhesive Interface Prevent Autoantibody-induced Acantholysis in Pemphigus*

    Science.gov (United States)

    Heupel, Wolfgang-Moritz; Müller, Thomas; Efthymiadis, Athina; Schmidt, Enno; Drenckhahn, Detlev; Waschke, Jens

    2009-01-01

    Pemphigus vulgaris (PV) autoantibodies directly inhibit desmoglein (Dsg) 3-mediated transinteraction. Because cellular signaling also seems to be required for PV pathogenesis, it is important to characterize the role of direct inhibition in pemphigus acantholysis to allow establishment of new therapeutic approaches. Therefore, we modeled the Dsg1 and Dsg3 sequences into resolved cadherin structures and predicted peptides targeting the adhesive interface of both Dsg3 and Dsg1. In atomic force microscopy single molecule experiments, the self-designed cyclic single peptide specifically blocked homophilic Dsg3 and Dsg1 transinteraction, whereas a tandem peptide (TP) consisting of two combined single peptides did not. TP did not directly block binding of pemphigus IgG to their target Dsg antigens but prevented PV-IgG-induced inhibition of Dsg3 transinteraction in cell-free (atomic force microscopy) and cell-based (laser tweezer) experiments, indicating stabilization of Dsg3 bonds. Similarly, PV-IgG-mediated acantholysis and disruption of Dsg3 localization in HaCaT keratinocytes was partially blocked by TP. This is the first evidence that direct inhibition of Dsg3 binding is important for PV pathogenesis and that peptidomimetics stabilizing Dsg transinteraction may provide a novel approach for PV treatment. PMID:19164289

  10. Heritability of thyroid peroxidase autoantibody levels in type 1 diabetes: evidence from discordant twin pairs

    Science.gov (United States)

    Wang, Bin; Hawa, Mohammed I.; Rijsdijk, Frühling V.; Fain, Pamela R.; Paschou, Stavroula A.; Boehm, Bernhard O.; Steck, Andrea K.; Snieder, Harold

    2016-01-01

    Aims/hypothesis The discordance status of (autoimmune) type 1 diabetes within monozygotic twin pairs points to the importance of environmental factors. The aim of this study was to investigate whether the environmental events causing type 1 diabetes influence thyroid autoimmunity. Methods Monozygotic and dizygotic twins discordant for type 1 diabetes from the UK and USA were tested for thyroid peroxidase autoantibodies (TPOA) by radioimmunoassay. Using quantitative genetic model fitting of a liability-threshold model we estimated the contribution of genetic (heritability) and environmental factors to TPOA. Results TPOA positivity was higher in females than in males in both cohorts and was associated with later age at diagnosis in the UK and combined cohorts (p0.2 in all groups). The best-fitting models showed heritability (95% CI) estimates for TPOA of 63% (37%, 80%) for the UK and 80% (51%, 92%) for US twins, while the best-fitting meta-analysis model of the two twin cohorts combined included additive genetic and unique environmental factors with a heritability estimate of 69% (50%, 82%). Conclusions/interpretation Risk of thyroid autoimmunity, defined by TPOA, in the context of autoimmune diabetes is, substantially, genetically determined in discordant twin pairs. Environmental factors leading to type 1 diabetes were not the same as those involved with thyroid autoimmunity. It follows that it is as important to investigate for thyroid autoimmunity in relatives of type 1 diabetes patients as it is in the patients themselves. PMID:26070305

  11. 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.

  12. Blocking and Binding Folate Receptor Alpha Autoantibodies Identify Novel Autism Spectrum Disorder Subgroups.

    Science.gov (United States)

    Frye, Richard E; Delhey, Leanna; Slattery, John; Tippett, Marie; Wynne, Rebecca; Rose, Shannon; Kahler, Stephen G; Bennuri, Sirish C; Melnyk, Stepan; Sequeira, Jeffrey M; Quadros, Edward

    2016-01-01

    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 and 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. PMID:27013943

  13. Autoantibodies to Tailor-Made Panels of Tumor-Associated Antigens in Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Ettie Piura

    2011-01-01

    Full Text Available Autoantibodies (AAbs to tumor-associated antigens (TAAs have been identified in the sera of cancer patients. In a previous review published in this journal, we have focused on recent knowledge related to circulating AAbs to individual TAAs in breast carcinoma. This review will focus on recent knowledge related to AAb assays to tailor-made panels of TAAs in breast carcinoma. So far, AAb assays to the following tailor-made panels of TAAs have been assessed in breast carcinoma: (1 p53, c-myc, HER2, NY-ESO-1, BRCA2, and MUC1, (2 IMP1, p62, Koc, p53, c-MYC, cyclin B1, and survivin, (3 PPIA, PRDX2, FKBP52, HSP-60, and MUC1, (4 MUC1, HER2, p53, and IGFBP2, (5 p53, HER2, IGFBP-2, and TOPO2α, (6 survivin and livin, (7 ASB-9, SERAC1, and RELT, and (8 p16, p53, and c-myc. Assessment of serum AAbs to a tailor-made panel of TAAs provides better sensitivity to diagnosis of breast carcinoma than measuring serum AAbs to a single TAA. Nevertheless, measurement of serum AAbs to a panel of TAAs for screening and early diagnosis of breast carcinoma is still investigational and should be carried out along with traditional diagnostic studies.

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

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, A R; Diamant, Marcus; Nansen, A; Rieneck, K; Otterness, I G; Bendtzen, K

    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...... 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...... induced 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...

  15. A solid phase radioimmunoassay for detection of serum autoantibodies in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Solid phase radioimmunoassay (RIA) methods for measuring autoantibodies in systemic lupus erythematosus (SLE) patients' serum were developed to improve the sensitvity and quantitative precision of the determinations. Two mechanical systems were studied: (1) acetone fixed cell monolayers in glass tubes and (2) antigen coated plastic beads. Both systems were senssitive and reproducible. The most sensitive, versatile system involves the coating of the plastic beads with nuclear antigen(s), incubation overnight with sera and labelling with 125I conjugated antihuman globulin. Linear binding of this radioactive tag is obtained over a wide range of SLE serum dilutions and the slopes of the serum dilution titration curves are almost identical for all SLE patients' sera tested. Therefore, a standard titration curve can be constructed from the results with a positive serum, and end-point dilutions of unknown sera estimated from results obtained with a single serum dilution. Alternatively, binding ratios of unknown sera can be usefully compared at fixed dilutions with standard positive and negative sera. For example, high binding ratios (>3.0) were obtained with 19/20 SLE sera and 0/20 control sera. Antigens used in these systems include crude, whole-cell lysates and lysates from purified nuclei

  16. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

    DEFF Research Database (Denmark)

    Fosgerau, K; Galle, P; Hansen, Torben; Albrechtsen, A; Rieper, C de Lemos; Pedersen, B Klarlund; Larsen, L Kongskov; Thomsen, A Randrup; Pedersen, O; Hansen, M Bagge; Steensberg, A

    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...

  17. Prevalence and Regional Distribution of Autoantibodies Against GAD65Ab in a European Population Without Diabetes

    DEFF Research Database (Denmark)

    Rolandsson, Olov; Hampe, Christiane S; Wennberg, Patrik; Radtke, Jared; Langenberg, Claudia; Wareham, Nicholas

    2015-01-01

    Geographical differences in type 1 diabetes (T1D) prevalence in Europe have been well documented, but little is known about the geographical distribution of autoantibodies specific to GAD65 (GAD65Ab) in the general population without diabetes, which is reported to range between 0.4 and 3%. However......, these studies used different methods to define GAD65Ab positivity with cutoff values based on the 97–99th centile or at +3 SD above the mean among healthy individuals without T1D or type 2 diabetes (T2D). In doing so, the prevalence of GAD65Ab among the study cohorts was, by definition, 1–3%. The...... European countries and 2) compare characteristics of age, sex, and BMI in relation to GAD65Ab positivity. A center-stratified random subcohort of 16,835 (4.9%) individuals was selected from the original European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (1). After exclusion...

  18. 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. PMID:24391407

  19. [Evolution of autoantibodies profile in systemic lupus erythematosus according to age and clinical manifestations].

    Science.gov (United States)

    Diallo, Mariama Sadjo; Mbengue, Babacar; Seck, Abdoulaye; Ndao, Awa Cheikh; Niang, Maguette Sylla; Cissoko, Yacouba; Thiam, Alassane; Diop, Gora; Diallo, Rokhaya Ndiaye; Diallo, Moussa; Ndongo, Souhaibou; Dièye, Tandakha Ndiaye; Cissé, Mohamed; Kane, Assane; Dièye, Alioune

    2014-01-01

    Clinical features and auto-antibodies profile of 35 Senegalese patients' diagnosed systemic lupus erythematosus (SLE) were analyzed after measurement of antinuclear antibodies (ANA) by IFI, detection of Abs anti-DNA native by ELISA and evaluation of antibodies anti-Sm, anti-RNP, anti-SSA anti-SSB, anti-CCP2, anti-J0, and anti-Scl70 levels by immunodot. Mean age of 33 yrs (18-50 yrs) and sex ratio (F/M) of 16 were found. The most frequent clinical features were rheumatic (88.7%) and cutaneous (79.4%) disorders. ANA and anti-DNAn Abs were detected in 85.7% and 62.5% of the patients respectively. Abs anti-RNP, anti-Sm, anti-SSA, anti-SSB and anti-CCP2 were detected in 30 to 70% of patients. In young patients, the levels of anti-DNAn and anti-Sm Abs were higher than in patients older than 40 yrs (Panti-DNAn, anti-SSA and anti-SSB Abs. Our study shows the interest of a measurement of anti-DNAn, anti-SSA and anti-SSB Abs during the follow of SLE patients particularly in those presenting both rheumatic and cutaneous symptoms. PMID:24876146

  20. Development of a Recombinant Cell-Based Indirect Immunofluorescence Assay for the Determination of Autoantibodies against Soluble Liver Antigen in Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    Christiane Radzimski

    2013-01-01

    Full Text Available Autoantibodies against soluble liver antigen (SLA are specific markers for autoimmune hepatitis (AIH type 1. In contrast to the determination of other AIH-associated autoantibodies by indirect immunofluorescence assay (IFA, detection of anti-SLA relied up to now on ELISA or immunoblot based on bacterially expressed recombinant protein. In order to develop a complementary IFA substrate, SLA isoform 1 was recombinantly produced in the human cell line HEK293 and controlled by a rabbit hyperimmune serum against SLA. The recombinant cells were used in IFA (RC-IFA to analyze sera from 20 AIH patients with anti-SLA positivity predetermined by ELISA together with 80 controls (20 anti-SLA negative AIH, 15 primary biliary cirrhosis, 15 HCV, and 30 healthy blood donors. Using RC-IFA, anti-SLA was detected in all ELISA positive AIH sera but in none of the controls. Furthermore, a cytosolic fraction of HEK293 containing SLA was able to neutralize the autoantibodies in all positive sera in a dose-dependent manner. HEK293 cells expressing SLA are a valid substrate for the serodiagnosis of AIH relevant autoantibodies by IFA. In concert with cryosections of primate liver, rat kidney, rat liver, rat stomach, and HEp-2 cells, they enable the parallel determination of all autoantibodies associated with autoimmune liver diseases.

  1. Detection of adrenocortical autoantibodies in Addison's disease with a peroxidase-labelled protein A technique

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    R.C. Silva

    1998-09-01

    Full Text Available Adrenocortical autoantibodies (ACA, present in 60-80% of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13 and granulomatous (N = 9. ACA-PLPA were detected in 10/22 (45% patients: 9/13 (69% with the idiopathic form and 1/9 (11% with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50%: 10/13 (77% with the idiopathic form and 1/9 (11% with the granulomatous form. Twelve of the 13 idiopathic addisonians (92% were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time. However, since it is only 60% concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera.

  2. Potential relevance of alpha(1-adrenergic receptor autoantibodies in refractory hypertension.

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    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies directed at the alpha(1-adrenergic receptor (alpha(1-AAB have been described in patients with hypertension. We implied earlier that alpha(1-AAB might have a mechanistic role and could represent a therapeutic target. METHODOLOGY/PRINCIPAL FINDINGS: To pursue the issue, we performed clinical and basic studies. We observed that 41 of 81 patients with refractory hypertension had alpha(1-AAB; after immunoadsorption blood pressure was significantly reduced in these patients. Rabbits were immunized to generate alpha(1-adrenergic receptor antibodies (alpha(1-AB. Patient alpha(1-AAB and rabbit alpha(1-AB were purified using affinity chromatography and characterized both by epitope mapping and surface plasmon resonance measurements. Neonatal rat cardiomyocytes, rat vascular smooth muscle cells (VSMC, and Chinese hamster ovary cells transfected with the human alpha(1A-adrenergic receptor were incubated with patient alpha(1-AAB and rabbit alpha(1-AB and the activation of signal transduction pathways was investigated by Western blot, confocal laser scanning microscopy, and gene expression. We found that phospholipase A2 group IIA (PLA2-IIA and L-type calcium channel (Cacna1c genes were upregulated in cardiomyocytes and VSMC after stimulation with both purified antibodies. We showed that patient alpha(1-AAB and rabbit alpha(1-AB result in protein kinase C alpha activation and transient extracellular-related kinase (EKR1/2 phosphorylation. Finally, we showed that the antibodies exert acute effects on intracellular Ca(2+ in cardiomyocytes and induce mesentery artery segment contraction. CONCLUSIONS/SIGNIFICANCE: Patient alpha(1-AAB and rabbit alpha(1-AB can induce signaling pathways important for hypertension and cardiac remodeling. Our data provide evidence for a potential clinical relevance for alpha(1-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension.

  3. Autoantibodies to neuronal surface antigens in thyroid antibody-positive and -negative limbic encephalitis

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    Erdem Tuzun

    2011-01-01

    Full Text Available Background : Thyroid antibodies (Thy-Abs are frequently detected in various autoimmune disorders in coexistence with other systemic autoantibodies. In association with an encephalopathy, they are often taken as evidence of Hashimoto′s encephalitis (HE. However, the presence of Thy-Abs in a cohort of limbic encephalitis (LE patients and their association with anti-neuronal autoimmunity has not been explored. Patients and Methods : We investigated thyroid and anti-neuronal antibodies in the sera of 24 LE patients without identified tumors by cell-based assay and radioimmunoassay and evaluated their clinical features. Results : There was a female predominance in Thy-Ab-positive LE patients. Five of the eight Thy-Ab-positive patients and six of the 16 Thy-Ab-negative patients had antibodies to voltage-gated potassium channel (VGKC, N-methyl-D-aspartate receptor (NMDAR or undefined surface antigens on cultured hippocampal neurons. There were trends towards fewer VGKC antibodies (1/8 vs. 5/16, P = 0.159 and more NMDAR antibodies (2/8 vs. 1/16, P = 0.095 among the Thy-Ab-positive LE patients; antibodies to undefined surface antigens were only identified in Thy-Ab-positive patients (2/8 vs. 0/16, P = 0.018. There were no distinguishing clinical features between Thy-Ab-positive patients with and without neuronal antibodies. However, patients with anti-neuronal antibodies showed a better treatment response. Conclusion : Thy-Abs can be found in a high proportion of patients with non-paraneoplastic LE, often in association with antibodies to specific or as yet undefined neuronal surface antigens. These results suggest that acute idiopathic encephalitis patients with Thy-Abs should be closely monitored for ion-channel antibodies and it should not be assumed that they have HE.

  4. Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies

    International Nuclear Information System (INIS)

    Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important

  5. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells.

    Science.gov (United States)

    Bigler, Cornelia; Schaller, Monica; Perahud, Iryna; Osthoff, Michael; Trendelenburg, Marten

    2009-09-01

    Autoantibodies against complement C1q (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE). They strongly correlate with the occurrence of severe lupus nephritis, suggesting a pathogenic role in SLE. Because anti-C1q are known to recognize a neoepitope on bound C1q, but not on fluid-phase C1q, the aim of this study was to clarify the origin of anti-C1q by determining the mechanism that renders C1q antigenic. We investigated anti-C1q from serum and purified total IgG of patients with SLE and hypocomplementemic urticarial vasculitis as well as two monoclonal human anti-C1q Fab from a SLE patient generated by phage display. Binding characteristics, such as their ability to recognize C1q bound on different classes of Igs, on immune complexes, and on cells undergoing apoptosis, were analyzed. Interestingly, anti-C1q did not bind to C1q bound on Igs or immune complexes. Neither did we observe specific binding of anti-C1q to C1q bound on late apoptotic/necrotic cells when compared with binding in the absence of C1q. However, as shown by FACS analysis and confocal microscopy, anti-C1q specifically targeted C1q bound on early apoptotic cells. Anti-C1q were found to specifically target C1q bound on cells undergoing apoptosis. Our observations suggest that early apoptotic cells are a major target of the autoimmune response in SLE and provide a direct link between human SLE, apoptosis, and C1q. PMID:19648280

  6. Influence of anti-keratin autoantibodies on telomerase activity of squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    FU Meng; ZHANG Yan-guo; LIU Yu-feng; CHEN Yan; WANG Qiu-feng; LI Wei

    2002-01-01

    Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telomerase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on squamous cell carcinoma. Methods: Influence of AK auto Abs on the proliferation of Tca cells was observed by MTT colorimetry. Telomerase activity of cultured Tca cells and human keratinocytes was determined by telomeric repeat amplication protocol-ELISA (TRAP-ELISA) and polyacrylamide gel electrophoresis (PAGE). After being treated with AK auto Abs for 36 h at a concentration of 4, 8, 16 mg/L respectively, the changes of telomerase activity of Tca cells were also detected by TRAP-ELISA and PAGE.Results: MTT colorimetric determination showed that the capacity of proliferation of Tca cells correlated negatively with the concentration of AK auto Abs (r=-0. 74, P<0. 01). TRAP-ELISA and PAGE showed that telomerase activity of Tca cells increased significantly compared to that of cultured human keratinocytes(t=3. 5396, P<0. 01). AK auto Abs at a concentrations of 4, 8, 16 mg/L had significant dose-dependent inhibitory effects on telomerase activity of Tca cells (r=- 0. 8358, P<0. 01). Conclusion: AK auto Abs have a significant dose-dependent inhibitory effect on the proliferation of cultured Tca cells. AK auto Abs inhibit telomerase activity of cultured Tca cells with dose-dependent pattern. It suggests that decrease of telomerase activity may play an important role in the inhibitory effects of AK auto Aba on squamous cell carcinoma.

  7. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein.

    Science.gov (United States)

    Kakalacheva, Kristina; Regenass, Stephan; Wiesmayr, Silke; Azzi, Tarik; Berger, Christoph; Dale, Russell C; Brilot, Fabienne; Münz, Christian; Rostasy, Kevin; Nadal, David; Lünemann, Jan D

    2016-01-01

    A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM. PMID:26907324

  8. Glutamate receptor autoantibody concentrations in children with chronic post-traumatic headache.

    Science.gov (United States)

    Goryunova, A V; Bazarnaya, N A; Sorokina, E G; Semenova, N Yu; Globa, O V; Semenova, Zh B; Pinelis, V G; Roshal', L M; Maslova, O I

    2007-10-01

    We report here studies on the levels of autoantibodies (aAb) to AMPA glutamate receptors (GluR1 subunit) and NMDA glutamate receptors (NR2A subunit) in serum from 60 children aged 7-16 years with chronic posttraumatic headache (CPTHA) following mild craniocerebral trauma (CCT). The first group consisted of 48 children who had sustained cerebral concussion (CC), of which 34 had single-episode CC (subgroup 1a) and 14 had repeated CC (subgroup 1). The second group included 12 children with mild cerebral contusions (MCC). Serum glutamate receptor aAb levels were measured six months and one year after trauma. Increased aAb levels were expressed as percentages and were regarded as significant when increases were to 120% of the level seen in healthy children of the same age. The highest levels of aAb to NMDA receptors were seen in children with MCC (165 +/- 34%) and single CC (145 +/- 12.6%). Children with repeated CC had NMDA receptor aAb at normal levels (108 +/- 12.4%). Increases in NMDA receptor aAb were seen during the first year after trauma. Increases in AMPA receptor aAb were seen in children with repeated CC and MCC (150 +/- 16.8% and 167 +/- 31.3%). EEG studies showed that 18% of these children had nonspecific paroxysmal changes and 6% showed epileptiform activity. These results provide evidence that children with post-traumatic headache demonstrated hyperstimulation of glutamate receptors and overdevelopment of the autoimmune process. Increases in serum levels of aAb to NMDA glutamate receptors reflected hypoxic-ischemic brain lesions in children with CPTHA and dictate the need for these children to receive metabolic therapy. PMID:17922239

  9. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Autoantibodies.

    Science.gov (United States)

    Tung, K. S.; Smith, S.; Matzner, P.; Kasai, K.; Oliver, J.; Feuchter, F.; Anderson, R. E.

    1987-01-01

    In adult mice thymectomized at age 3 days (D3TX), increased incidences and/or levels of organ-specific antibodies to oocytes and/or zona pellucida, to testicular cell-sperm-differentiation antigens (TSDA), and to gastric parietal cells were detected, and these correlated significantly with oophoritis, orchitis (not epididymovasitis), and gastritis, respectively. The autoantibodies occurred in mice with the corresponding endogenous antigens. Thus, anti-oocyte/zona antibodies were detected in female, anti-TSDA antibodies in male, and anti-parietal cell antibodies in both sexes. Anti-oocyte/zona antibodies were first detected at age 5-6 weeks and were absent by 25 weeks. Serum antizona antibodies, but not anti-oocyte antibodies, inhibited mouse fertilization in vitro. In contrast, antibodies to sperm acrosome and antibodies to sperm surface did not correlate with testicular or epididymal disease. Moreover, both male and female mice had increased levels of anti-sperm surface antibodies, indicating that the sperm antigens detected may not be organ-specific. In addition, sera from 5-10% of D3TX mice reacted with a wide spectrum of epididymal and testicular antigens with defined cellular locations but of yet unknown specificity. Although the incidence of antibodies to cytoskeletal antigens was not significantly elevated after D3TX, anti-nuclear antibodies were more frequently detected in (SWR/J X A/J) F1 (SWRAF1) and (C57 BL/6J X A/J) F1 (B6AF1) mice after D3TX. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3826296

  10. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein

    Science.gov (United States)

    Kakalacheva, Kristina; Regenass, Stephan; Wiesmayr, Silke; Azzi, Tarik; Berger, Christoph; Dale, Russell C.; Brilot, Fabienne; Münz, Christian; Rostasy, Kevin; Nadal, David; Lünemann, Jan D.

    2016-01-01

    A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM. PMID:26907324

  11. Aquaporin-4 autoantibodies in Neuromyelitis Optica: AQP4 isoform-dependent sensitivity and specificity.

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    Francesco Pisani

    Full Text Available Neuromyelitis Optica (NMO is an autoimmune demyelinating disease, characterized by the presence of autoantibody (NMO-IgG to Aquaporin-4 (AQP4. NMO-IgG identification supports NMO diagnosis and several diagnostic tests have been developed, but their sensitivity is too variable, and some assay show low sensitivity. This impairs correct diagnosis of NMO. By cell based assay (CBA we here evaluate the efficacy of different strategies to express AQP4 in mammalian cells in terms of: a AQP4 translation initiation signals; b AQP4 isoforms (M1 and M23 and fluorescent tag position; c NMO serum concentration and AQP4 degradation. Our results demonstrate that when using AQP4-M1, the nucleotide in position -3 of the AUG greatly affects the AQP4-M1/M23 protein ratio, NMO-IgG binding, and consequently test sensitivity. Test sensitivity was highest with M23 expressing cells (97.5% and only 27.5% with AQP4-M1. The fluorescent tag added to the N-terminus of AQP4-M23 considerably affected the NMO-IgG binding, and test sensitivity, due to disruption of AQP4 suprastructures. Furthermore, sera used at high concentration resulted in AQP4 degradation which affected test sensitivity. To further evaluate the reliability of the M23 based CBA test, samples of one NMO patient collected during about 2 years clinical follow-up were tested. The results of serum titer correlated with disease activity and treatment response. In conclusion, we provide a molecular explanation for the contrasting CBA test data reported and suggest the use of M23 with a C-terminus fluorescent tag as the proper test for NMO diagnosis.

  12. B-cell subsets, signaling and their roles in secretion of autoantibodies.

    Science.gov (United States)

    Iwata, S; Tanaka, Y

    2016-07-01

    B cells play a pivotal role in the pathogenesis of autoimmune diseases. In patients with systemic lupus erythematosus (SLE), the percentages of plasmablasts and IgD(-)CD27(-) double-negative memory B cells in peripheral blood are significantly increased, while IgD(+)CD27(+) IgM memory B cells are significantly decreased compared to healthy donors. The phenotypic change is significantly associated with disease activity and concentration of autoantibodies. Treatment of B-cell depletion using rituximab results in the reconstitution of peripheral B cells in SLE patients with subsequent improvement in disease activity. Numerous studies have described abnormalities in B-cell receptor (BCR)-mediated signaling in B cells of SLE patients. Since differences in BCR signaling are considered to dictate the survival or death of naïve and memory B cells, aberrant BCR signal can lead to abnormality of B-cell subsets in SLE patients. Although Syk and Btk function as key molecules in BCR signaling, their pathological role in SLE remains unclear. We found that Syk and Btk do not only transduce activation signal through BCR, but also mediate crosstalk between BCR and Toll-like receptor (TLR) as well as BCR and JAK-STAT pathways in human B cells in vitro. In addition, pronounced Syk and Btk phosphorylation was observed in B cells of patients with active SLE compared to those of healthy individuals. The results suggest the involvement of Syk and Btk activation in abnormalities of BCR-mediated signaling and B-cell phenotypes during the pathological process of SLE and that Syk, Btk and JAK are potential therapeutic targets in SLE. PMID:27252261

  13. Protective effect of naturally occurring anti-HER2 autoantibodies on breast cancer.

    Science.gov (United States)

    Tabuchi, Yukiko; Shimoda, Masafumi; Kagara, Naofumi; Naoi, Yasuto; Tanei, Tomonori; Shimomura, Atsushi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

    2016-05-01

    Anti-HER2-autoantibodies (HER2-AAbs) are found in breast cancer patients as well as healthy individuals. However, the clinical relevance of the antibodies is unknown. We established an enzyme-linked immunosorbent assay with high sensitivity and quantified serum HER2-AAbs in 100 healthy women, 100 untreated patients with ductal carcinoma in situ (DCIS), and 500 untreated patients with invasive breast carcinoma (IBC). The associations between the levels of HER2-AAbs and breast cancer risk, and recurrence-free survival, were examined. High levels of HER2-AAbs were significantly associated with a reduced risk of DCIS (odds ratio [OR] 0.19, P = 4.6 × 10(-7)) or IBC (OR 0.31, P = 3.7 × 10(-7)). Subgroup analysis of IBC revealed a stronger association of HER2-AAbs with a reduced risk of the hormone receptor (HR)(-)/HER2(+) subtype (OR 0.12) than the other subtypes (HR(+)/HER2(-) [OR = 0.32], HR(+)/HER2(+) [OR 0.38], and HR(-)/HER2(-) [OR 0.29]). When we set the cutoff of HER2-AAbs at 20 ng/mL, recurrence-free survival of HER2-AAb-positive patients (N = 74) was significantly better than that of HER2-AAb-negative patients (N = 426) (P = 0.015). Univariate and multivariate analyses demonstrated that HER2-AAbs, as well as histological grade, were independently and significantly (P = 0.0065 and 0.049, respectively) associated with recurrence-free survival. Our exploratory study suggests a protective effect of naturally occurring HER2-AAbs on the development of primary and recurrent breast cancer. Further studies on HER2-AAbs are warranted. PMID:27113738

  14. Glutamic acid decarboxylase 65 autoantibody levels discriminate two subtypes of latent autoimmune diabetes in adults

    Institute of Scientific and Technical Information of China (English)

    李霞; 杨琳; 周智广; 黄干; 颜湘

    2003-01-01

    Objective To compare the clinical characteristics between type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) with different titers of glutamic acid decarboxylase autoantibody (GADA) and to define the two distinct subtypes of LADA.Methods Sera of 750 patients with an initial diagnosis of T2DM from central south of China were screened for GADA using a radioligand assay. The distribution and frequency of GADA levels were described. Two hundred and ninety-five patients were divided into the T2DM group (n=233) and the LADA group (n=62) to compare the age of onset, body mass index, HbA1c, C-peptide, hypertension, dyslipidemia and chronic diabetic complications. Furthermore, LADA patients with different GADA titers were subdivided to analyze the same indexes as the above. Results The prevalence of LADA (defined as GADA≥0.05, namely GADA positive) was 9.7% in the 750 initially diagnosed type 2 diabetic patients. Compared with T2DM, LADA patients were younger at their ages of onset, had lower C-peptide and body mass index, and also had less cases with hypertension and with dyslipidemia. However, only patients with high titer of GADA had poorer beta cell functions and less diabetic complications compared to T2DM and low GADA titer of LADA patients. Patients with low GADA titer were similar to T2DM patients, except that they were prone to develop ketosis more frequently.Conclusions Two clinically distinct subtypes of LADA can be identified by GADA levels in patients initially-diagnosed as type 2 diabetes. Patients with high titer of GADA (GADA≥0.5) subsequently develop more insulin dependency, which are classified as LADA-type 1; while those with lower GADA titer (0.05≤GADA<0.5) and having clinical and metabolic phenotypes of type 2 diabetes are classified as LADA-type 2.

  15. Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy

    International Nuclear Information System (INIS)

    The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with betamethasone from 3 weeks before until 4 weeks after 131I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the 131I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease

  16. Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gamstedt, A.; Karlsson, A. (Department of Internal Medicine, Orebro Medical Center Hospital (Sweden))

    1991-07-01

    The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with betamethasone from 3 weeks before until 4 weeks after {sup 131}I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the {sup 131}I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease.

  17. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy

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    Wang Yujuan

    2012-11-01

    Full Text Available Abstract Background Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively

  18. PRODUCTION OF CROSS-REACTIVE AUTOANTIBODY BINDING TO BOVINE SERUM ALBUMIN IN THE D-GALACTOSE-INDUCED AGING MOUSE MODEL

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    Ji-Hun Park

    2014-01-01

    Full Text Available The D-galactose (D-gal-induced animal model, generated by repeated subcutaneous D-gal injections over approximately 6 weeks, has been frequently used for diabetes and aging research. However, little research has investigated the direct correlation between D-gal and autoantibody formation despite several reports on diabetes-and aging-related autoantibodies. The purpose of this study was to determine whether repetitive injection of D-gal can induce autoantibody production in mice. First, we used Bovine Serum Albumin (BSA and Advanced Glycation End products (AGE-BSA as the test antigens. The immunoreactivity of serum samples from mice treated with D-gal for 6 weeks was evaluated using Enzyme-Linked Immunosorbent Assay (ELISA. We found that serum samples of D-gal-treated mice had significantly high antibody titers against both BSA and AGE-BSA. Furthermore, the result showed that aminoguanidine treatment, an AGE inhibitor tended to decrease this immunoreactivity. The results of competitive inhibition ELISA using BSA and AGE-BSA as the competitors suggested that the serum samples from D-gal-treated mice contained antibodies not only against BSA but also specific to AGE-BSA. To assess whether the immunoreactivity against BSA is comparable to that against Mouse Serum Albumin (MSA, we examined the reactivity of D-gal-induced antibodies against MSA. Unexpectedly, D-gal-induced antibodies did not react with MSA. This suggests that the production of antibodies by D-gal is in response to an unknown antigen(s, aside from MSA, in mice and that this unknown antigen(s may share similar sequences or three-dimensional structures with BSA.

  19. Thyroid autoantibodies and thyroid function in subjects exposed to Chernobyl fallout during childhood: evidence for a transient radiation-induced elevation of serum thyroid antibodies without an increase in thyroid autoimmune disease

    DEFF Research Database (Denmark)

    Agate, Laura; Mariotti, Stefano; Elisei, Rossella;

    2008-01-01

    An increase in the prevalence of thyroid autoantibodies (ATAs) was reported 6-8 yr after the Chernobyl accident in radiation-exposed children and adolescents.......An increase in the prevalence of thyroid autoantibodies (ATAs) was reported 6-8 yr after the Chernobyl accident in radiation-exposed children and adolescents....

  20. Possible Association of HLA-DRB1 Gene with the Autoantibody against Myocardial Mitochondria ADP/ATP Carrier in Dilated Cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    王秋芬; 廖玉华; 龚非力; 毛焕元; 张金枝

    2002-01-01

    Summary: To probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA-DRB1 gene polymorphism were analyzed by using the polymerase chain reaction /sequence specific primer (PCR/SSP) technique and autoantibody against myocardial mitochondria ADP/ATP carrier were examined by using the Immunoblot analysis. The frequency of HLA-DRB1 * 0901 allele was significantly higher in DCM patients in which autoantibody against ADP/ATP carrier of myocardial mitochondria is positive in contrast with those in which the autoantibody is negative (25.46 % vs 3.45 %, P<0.05), the relative risk (RR) being 9.56. The other frequencies of HLA-DRB1 alleles have no significant difference in the antibody positive group and negative group. It is possible that a subset of DCM patients may exist in which autoimmunity is associated with genetic factors.

  1. Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors.

    OpenAIRE

    Nagayama, Y; Wadsworth, H L; Russo, D.; Chazenbalk, G D; Rapoport, B

    1991-01-01

    We examined the relative effects of thyrotropin (TSH) and TSH receptor autoantibodies in the sera of patients with autoimmune thyroid disease on three TSH-lutropin/chorionic gonadotropin (LH/CG) receptor extracellular domain chimeras. Each chimera binds TSH with high affinity. Only the chimera with TSH receptor extracellular domains ABC (amino acids 1-260) had a functional (cAMP) response to thyroid stimulatory IgG. The chimeras with TSH receptor domains CD (amino acids 171-360) and DE (amino...

  2. Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease

    OpenAIRE

    Hof, D.; Cheung, K.; de Rooij, D J R A M; Hoogen, F.H.J. van den; Pruijn, G J M; Venrooij, W.J.W. van; Raats, J.M.H.

    2005-01-01

    Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent. During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibo...

  3. Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma

    OpenAIRE

    Dong Jun; Zeng Bo-hang; Xu Li-hua; Wang Jun-ye; Li Man-Zhi; Zeng Mu-sheng; Liu Wan-li

    2010-01-01

    Abstract Background The oncogene CDC25B phosphatase plays an important role in cancer cell growth. We have recently reported that patients with esophageal squamous cell carcinoma (ESCC) have significantly higher serum levels of CDC25B autoantibodies (CDC25B-Abs) than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical significance of serum CD...

  4. Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis

    International Nuclear Information System (INIS)

    The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA

  5. 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 patien...... recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti...

  6. Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Tanay, A.; Schiffman, G.; Strober, S.

    1986-01-01

    The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA.

  7. Role of intermolecular/intrastructural B- and T-cell determinants in the diversification of autoantibodies to ribonucleoprotein particles.

    OpenAIRE

    Fatenejad, S; Mamula, M J; Craft, J.

    1993-01-01

    The U1 small nuclear ribonucleoprotein (sn-RNP) particle, which consists of the U1 small RNA and multiple polypeptides, is a central target of the autoimmune response in systemic lupus erythematosus. Autoantibodies to the individual proteins of the U1 snRNP typically co-occur in patients with systemic lupus erythematosus, an observation reconciled by postulating that the intact RNA-protein complex serves as the autoimmunogen and that snRNP-specific autoreactive T cells are necessary for autoa...

  8. Monoclonal anti-IgG autoantibodies derived from lipopolysaccharide-activated spleen-cells of 129/Sv mice

    OpenAIRE

    Van Snick, Jacques 34846 Auteur UCL; Coulie, Pierre 30218 UCL

    1982-01-01

    In some colonies, 129/Sv mice produce, upon aging, a rheumatoid factor (RF) that is specific for mouse IgG2a but fails to react with IgG2a of the b allotype. It is not known whether this narrow specificity is due to the absence of other RF specificities in the repertoire of these mice or to the selective activation of the production of anti-IgG2a autoantibodies by a specific stimulus. To analyze the RF repertoire of 129/Sv mice, we have derived hybridomas from their spleen cells 3 d after an ...

  9. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo.

    Science.gov (United States)

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E; Borza, Dorin-Bogdan

    2010-09-15

    The noncollagenous (NC1) domains of alpha3alpha4alpha5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of alpha3alpha4alpha5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine alpha3alpha4alpha5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b(-/-) mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine alpha3NC1 monomer and dimer subunits but not to native alpha3alpha4alpha5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked alpha3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of alpha3alpha4alpha5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen. PMID:20709951

  10. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: Protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo 1

    Science.gov (United States)

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E.; Borza, Dorin-Bogdan

    2010-01-01

    The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport post-transplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM antibodies. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to antibody-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 cross-links, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys—a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by post-translational modifications of an autoantigen. PMID:20709951

  11. Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara

    OpenAIRE

    Petri, Marcelo H.; Satoh, Minoru; Martin-Marquez, Beatriz T; Vargas-Ramírez, Raul; Jara, Luis J; Saavedra, Miguel A; Cruz-Gonzalez, Claudia; Andrade-Ortega, Lilia; Vera-Lastra, Olga; Salazar-Páramo, Mario; Prieto-Parra, Rosa E; Gonzalez-Lopez, Laura; Gamez-Nava, Jorge I; Hermes U. Ramírez-Sánchez; Chan, Jason YF

    2013-01-01

    Introduction Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico. Methods Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were...

  12. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

    2004-01-01

    B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto's thyroidi......B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto...

  13. Purification and characterization of human autoantibodies directed to specific regions on U1RNA; recognition of native U1RNP complexes.

    OpenAIRE

    Hoet, R M; Kastner, B; Lührmann, R; van Venrooij, W J

    1993-01-01

    Antibodies against naked U1RNA can be found in sera from patients with overlap syndromes of systemic lupus erythematosus (SLE) in addition to antibodies directed to the proteins of U1 ribonucleoproteins (U1RNP). We investigated the reactivity of these U1RNA specific autoantibodies with the native U1RNP particle both in vitro and inside the cell. For this purpose a method was developed to purify human autoantibodies directed to specific regions of U1RNA. The antibodies are specifically directe...

  14. Aptamer BC007 for neutralization of pathogenic autoantibodies directed against G-protein coupled receptors: A vision of future treatment of patients with cardiomyopathies and positivity for those autoantibodies.

    Science.gov (United States)

    Wallukat, Gerd; Müller, Johannes; Haberland, Annekathrin; Berg, Sabine; Schulz, Angela; Freyse, Ernst-Joachim; Vetter, Roland; Salzsieder, Eckhard; Kreutz, Reinhold; Schimke, Ingolf

    2016-01-01

    Cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas' cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) that agonistically activate their receptors. For the treatment of "agonistic autoantibody diseases" and in particular DCM, the removal of the GPCR-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC007 for in vivo neutralization of GPCR-AABs could help. We demonstrate here, that the aptamer neutralized, in vitro, the presently known cardiovascular-pathogenic GPCR-AABs. In spontaneously hypertensive rats, the aptamer demonstrated its GPCR-AAB neutralizing potency in vivo. In the serum of DCM patients, the same GPCR-AAB reduction was achieved when patients were either immunoadsorbed or patient's serum was ex vivo treated with the aptamer. In our view, aptamer BC007 treatment in GPCR-AAB-positive patients would have a comparable benefit as that seen after IA. Not knowing all that interfering with our idea of aptamer-dependent neutralization of GPCR-AABs, the first preliminary steps have been taken for bringing the idea closer to patients. PMID:26584137

  15. Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Bogdanos Dimitrios P

    2012-08-01

    Full Text Available Abstract Background Glycoprotein 2 (GP2 was discovered as the major autoantigen of Crohn’s disease (CD-specific pancreatic autoantibodies (PAB. We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes. Methods Anti-GP2 and anti-Saccharomyces cerevisiae (ASCA IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF in 271 sera, 169 with CD and 102 with ulcerative colitis (UC. As healthy controls 160 adult blood donors and 65 children were included. Results Anti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2% than in UC (9/102, 8.9% patients and in controls (9/225, 4% (p  Conclusions Anti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.

  16. Identification of Ki (Ku, p70/p80) autoantigens and analysis of anti-Ki autoantibody reactivity

    International Nuclear Information System (INIS)

    Anti-Ki (Ku, p70/p80) autoantibodies, named after the prototype patient Kikuta by Tojo et al., occur in approximately 10% of patients with SLE, often in association with anti-Sm autoantibodies. Anti-Ki sera specifically immunoprecipitated two protein antigens, Ki86 (M/sub r/ 86,000) and Ki66 (M/sub r/ 66,000), from radiolabeled cell extracts. The Ki system was found to be immunologically identical to the Ku system described by Mimori et al. and the p70/p80 system described by Reeves. The Ki primary in vitro translation products were identified and proved similar in size to the cellular antigens. The Ki antigens were purified from human spleen by immunoaffinity chromatography followed by SDS-PAGE. The purified Ki antigens proved to be closely related by amino acid composition, and did not appear to be phosphorylated, glycosylated, or associated with RNA. The Ki antigens were found to bind to DNA, in agreement with the observations on the Ku and p70/p80 antigens. They were found to be widely conserved in mammals and were coordinately expressed in all tissues tested

  17. Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

    Directory of Open Access Journals (Sweden)

    Gamal Badra

    2006-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4 is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5% patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32% previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.

  18. High Prevalence of Neutrophil Cytoplasmic Autoantibodies in Infants with Food Protein-Induced Proctitis/Proctocolitis: Autoimmunity Involvement?

    Directory of Open Access Journals (Sweden)

    Alena Sekerkova

    2015-01-01

    Full Text Available Background. Food protein-induced proctitis/proctocolitis (FPIP is the most common noninfectious colitis in children in the first year of life. Along with the overall clinical symptoms, diarrhoea and rectal bleeding are the main manifestations of the disease. There is no routine noninvasive test that would be specific for this type of colitis. The aim of our study was to find a noninvasive laboratory test or tests that may be helpful in differential diagnosis of food protein-induced proctitis/proctocolitis. Methods. ANA, ANCA, ASCA, a-EMA, a-tTg, specific IgE, total IgE, IgG, IgA, IgM, and concentration of serum calprotectin were measured in a group of 25 patients with colitis and 18 children with other diagnoses. Results. Atypical-pANCA antibodies of IgG isotype were detected in the sera of 24 patients by the method of indirect immunofluorescence, and 5 patients showed also the positivity of IgA isotype. In control samples these autoantibodies were not detected. Other autoantibodies were not demonstrated in either patient or control group. Conclusions. Of the parameters tested in noninfectious colitis, atypical-pANCA on ethanol-fixed granulocytes appears to be a suitable serological marker of food protein-induced proctitis/proctocolitis and suggests a possible involvement of an autoimmune mechanisms in the pathogenesis of this disease.

  19. Detection of multiple annexin autoantibodies in a patient with recurrent miscarriages, fulminant stroke and seronegative antiphospholipid syndrome.

    Science.gov (United States)

    Scholz, Philipp; Auler, Markus; Brachvogel, Bent; Benzing, Thomas; Mallman, Peter; Streichert, Thomas; Klatt, Andreas R

    2016-01-01

    Anti-phospholipid syndrome (APS) is one of the main causes for recurrent miscarriages. The diagnosis of APS is based on the occurrence of clinical symptoms such as thrombotic events or obstetric complications as well as the detection of antiphospholipid antibodies directed against β2-glycoprotein I and cardiolipin, or a positive lupus anticoagulant assay. However, there is a subpopulation of patients with clinical symptoms of APS, but the lack of serological markers (seronegative APS). In addition, a large proportion of patients with unexplained recurrent miscarriages exist. These cases may be attributed, at least in part, to a seronegative APS.
The presence of autoantibodies against annexins is potentially associated with APS. Here we used immunoassays and immunoblots to detect autoantibodies directed against annexin A1-5, and A8, respectively, in a patient with a seronegative APS and a history of six recurrent pregnancy losses and fulminant stroke. We found strong IgM isotype antibody reactivity directed against annexin A2 and annexin A8, and moderate to weak IgM isotype antibody reactivity directed against annexin A1, A3, and A5. Further studies will evaluate the diagnostic value of IgM isotype antibodies against annexin A1-A5, and A8 for seronegative APS and recurrent miscarriages. PMID:27346975

  20. The Value of a Panel of Autoantibodies for Predicting the Activity of Lupus Nephritis at Time of Renal Biopsy

    Directory of Open Access Journals (Sweden)

    Gabriella Moroni

    2015-01-01

    Full Text Available Few studies have correlated serum biomarkers with renal histology, the gold standard for renal activity, in lupus nephritis (LN. We tested a panel of autoantibodies and complement at the time of kidney biopsy and after treatment. Anti-dsDNA, anti-nucleosome, anti-ribosome P, and anti-C1q antibodies and C3/C4 were measured in 107 patients with LN at the time of renal biopsy and after 6–12 months and were correlated with clinical/histological parameters. At multivariate analysis, high titers of anti-C1q antibodies or of anti-dsDNA antibodies (P=0.005, OR = 8.67, CI: 2.03–37.3 were the independent predictors that discriminate proliferative from nonproliferative LN. All the immunological parameters, except anti-ribosome, showed a significant correlation with activity index but not with chronicity index. Only anti-C1q showed a significant correlation with the amount of proteinuria (R=0.2, P=0.03. None of the immunological parameters were predictive of remission at 6 and 12 months. We found that anti-C1q alone or in combination with anti-dsDNA emerged as the most reliable test in differentiating proliferative and nonproliferative LN. Anti-C1q was the only test correlated with the clinical presentation of LN. After treatment, the titre of the autoantibodies was significantly reduced, but none was predictive of remission.

  1. A rapid lateral flow immunoassay for the detection of tyrosine phosphatase-like protein IA-2 autoantibodies in human serum.

    Directory of Open Access Journals (Sweden)

    Ingrid Kikkas

    Full Text Available Type 1 diabetes (T1D results from the destruction of pancreatic insulin-producing beta cells and is strongly associated with the presence of islet autoantibodies. Autoantibodies to tyrosine phosphatase-like protein IA-2 (IA-2As are considered to be highly predictive markers of T1D. We developed a novel lateral flow immunoassay (LFIA based on a bridging format for the rapid detection of IA-2As in human serum samples. In this assay, one site of the IA-2As is bound to HA-tagged-IA-2, which is subsequently captured on the anti-HA-Tag antibody-coated test line on the strip. The other site of the IA-2As is bound to biotinylated IA-2, allowing the complex to be visualized using colloidal gold nanoparticle-conjugated streptavidin. For this study, 35 serum samples from T1D patients and 44 control sera from non-diabetic individuals were analyzed with our novel assay and the results were correlated with two IA-2A ELISAs. Among the 35 serum samples from T1D patients, the IA-2A LFIA, the in-house IA-2A ELISA and the commercial IA-2A ELISA identified as positive 21, 29 and 30 IA-2A-positive sera, respectively. The major advantages of the IA-2A LFIA are its rapidity and simplicity.

  2. Two new cases of anti-Ca (anti-ARHGAP26/GRAF autoantibody-associated cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Jarius Sven

    2013-01-01

    Full Text Available Abstract Recently, we discovered a novel serum and cerebrospinal fluid (CSF autoantibody (anti-Ca to Purkinje cells in a patient with autoimmune cerebellar ataxia (ACA and identified the RhoGTPase-activating protein 26 (ARHGAP26; alternative designations include GTPase regulator associated with focal adhesion kinase pp125, GRAF, and oligophrenin-1-like protein, OPHN1L as the target antigen. Here, we report on two new cases of ARHGAP26 autoantibody-positive ACA that were first diagnosed after publication of the index case study. While the index patient developed ACA following an episode of respiratory infection with still no evidence for malignancy 52 months after onset, neurological symptoms heralded ovarian cancer in one of the patients described here. Our finding of anti-Ca/anti-ARHGAP26 antibodies in two additional patients supports a role of autoimmunity against ARHGAP26 in the pathogenesis of ACA. Moreover, the finding of ovarian cancer in one of our patients suggests that anti-Ca/anti-ARHGAP26-positive ACA might be of paraneoplastic aetiology in some cases. In conclusion, testing for anti-Ca/anti-ARHGAP26 should be included in the diagnostic work-up of patients with ACA, and an underlying tumour should be considered in patients presenting with anti-Ca/ARHGAP26 antibody-positive ACA.

  3. Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting.

    Science.gov (United States)

    Chen, Hongda; Werner, Simone; Butt, Julia; Zörnig, Inka; Knebel, Phillip; Michel, Angelika; Eichmüller, Stefan B; Jäger, Dirk; Waterboer, Tim; Pawlita, Michael; Brenner, Hermann

    2016-03-29

    Novel blood-based screening tests are strongly desirable for early detection of colorectal cancer (CRC). We aimed to identify and evaluate autoantibodies against tumor-associated antigens as biomarkers for early detection of CRC. 380 clinically identified CRC patients and samples of participants with selected findings from a cohort of screening colonoscopy participants in 2005-2013 (N=6826) were included in this analysis. Sixty-four serum autoantibody markers were measured by multiplex bead-based serological assays. A two-step approach with selection of biomarkers in a training set, and validation of findings in a validation set, the latter exclusively including participants from the screening setting, was applied. Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage CRC and advanced adenoma. Multi-marker combinations substantially increased sensitivity at the price of a moderate loss of specificity. Anti-TP53, anti-IMPDH2, anti-MDM2 and anti-MAGEA4 were consistently included in the best-performing 4-, 5-, and 6-marker combinations. This four-marker panel yielded a sensitivity of 26% (95% CI, 13-45%) for early stage CRC at a specificity of 90% (95% CI, 83-94%) in the validation set. Notably, it also detected 20% (95% CI, 13-29%) of advanced adenomas. Taken together, the identified biomarkers could contribute to the development of a useful multi-marker blood-based test for CRC early detection. PMID:26909861

  4. MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice

    Directory of Open Access Journals (Sweden)

    Pan Y

    2012-12-01

    Full Text Available Yang Pan,1,2 Tingting Jia,1,2 Yuan Zhang,1,2 Kuo Zhang,1 Rui Zhang,1 Jinming Li,1 Lunan Wang11National Center for Clinical Laboratories, Beijing Hospital of the Ministry of Health, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaBackground: Systemic lupus erythematosus (SLE is a chronic autoimmune disease characterized by the presence of pathogenic autoantibodies. Recent studies suggest that microRNAs (miRNAs play an essential role in immunoregulation and may be involved in the pathogenesis of SLE. Therefore, it was of interest to investigate the potential therapeutic application of miRNAs in SLE, a concept that has not been thoroughly investigated thus far. Virus-like particles (VLPs are a type of recombinant nanoparticle enveloped by certain proteins derived from the outer coat of a virus. Herein, we describe a novel miRNA-delivery approach via bacteriophage MS2 VLPs and investigate the therapeutic effects of miR-146a, a well-studied and SLE-related miRNA, in BXSB lupus-prone mice.Methods: VLPs containing miR-146a, and the control VLPs, were prepared using an Escherichia coli expression system and then administered to lupus-prone mice over a 12-day period. We performed an enzyme-linked immunosorbent assay to evaluate the anti-dsDNA antibody, autoantibody to nuclear antigen (ANA, total IgG and total IgM levels in serum. The expression of miR-146a was analyzed by qRT-PCR. SLE-related cytokines as well as some toll-like receptor signaling pathway molecules were also measured.Results: Treatment with MS2-miR146a VLP showed profound effects on lupus-prone BXSB mice, including an increased level of mature miR-146a, which led to a significant reduction in the expression of autoantibodies and total IgG. Remarkably, these mice also exhibited reduced levels of proinflammatorycytokines, including IFN-Interferon-α (IFN-α, Interleukin-1β (Il-1

  5. Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

    Institute of Scientific and Technical Information of China (English)

    Stephan Gehring; Ulrike Kullmer; Sabine Koeppelmann; Patrick Gerner; Philip Wintermeyer; Stefan Wirth

    2006-01-01

    AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity.METHODS: We investigated the prevalence of autoantibodies in 123 chronic HCV-infected children before,during and after monotherapy with interferon-alpha (TFN-α) or combined treatment with interferon-α or peginterferon-α and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (LKM), the incidence of antithyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined.RESULTS: We found that 8% of children had autoantibodies before treatment. During treatment,18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-α treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism.CONCLUSION: Our data indicate a strong correlation between interferon-α treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.

  6. Monozygotic twin pairs discordant for Hashimoto's thyroiditis share a high proportion of thyroid peroxidase autoantibodies to the immunodominant region A. Further evidence for genetic transmission of epitopic "fingerprints"

    DEFF Research Database (Denmark)

    Brix, Thomas Heiberg; Hegedüs, Laszlo; Gardas, Andrzej; Banga, J Paul; Nielsen, Claus H

    2011-01-01

    Thyroid peroxidase antibodies (TPOAbs) in patients with Hashimoto's thyroiditis (HT) predominantly react with two immunodominant regions (IDR-A, IDR-B). Theoretically, as shown for the level of TPOAbs, the autoantibody epitopic recognition of the IDRs could be under genetic control. To examine th...

  7. Combination of autoantibodies against different histone proteins influences complement-dependent phagocytosis of necrotic cell material by polymorphonuclear leukocytes in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Gullstrand, Birgitta; Lefort, Malin H; Tydén, Helena; Jönsen, Andreas; Lood, Christian; Johansson, Asa; Jacobsen, Søren; Truedsson, Lennart; Bengtsson, Anders A

    2012-01-01

    Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as...... well as association to disease activity and clinical phenotype in SLE....

  8. Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy

    NARCIS (Netherlands)

    Dahnrich, C.; Komorowski, L.; Probst, C.; Seitz-Polski, B.; Esnault, V.; Wetzels, J.F.M.; Hofstra, J.M.; Hoxha, E.; Stahl, R.A.K.; Lambeau, G.; Stocker, W.; Schlumberger, W.

    2013-01-01

    BACKGROUND: Autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) are specific markers for primary membranous nephropathy (pMN) and anti-PLA2R1 serum levels may be useful to monitor disease activity. So far, a recombinant cell-based indirect immunofluorescence assay (RC-IFA) using rec

  9. Production of Autoantibodies in Chronic Hepatitis B Virus Infection Is Associated with the Augmented Function of Blood CXCR5+CD4+ T Cells.

    Science.gov (United States)

    Lei, Yu; Hu, Tingting; Song, Xiaofei; Nie, Hong; Chen, Min; Chen, Weixian; Zhou, Zhi; Zhang, Dazhi; Hu, Huaidong; Hu, Peng; Ren, Hong

    2016-01-01

    T follicular helper cells (Tfh) provide help to B cells to support their activation, expansion and differentiation. However, the role of Tfh cells in chronic HBV infection is poorly defined. The aim of this research was to examine the function of Tfh cells and whether they are involved in HBV related disease. Blood CXCR5+CD4+T cells and B cells in 85 patients with chronic HBV infection (HBV patients) and health controls (HC) were examined by flow cytometry. The molecule expression in blood CXCR5+CD4+ T cells was detected by real-time PCR. Blood CXCR5+CD4+ T cells and B cells were co-cultured and the production of Ig and cytokines was detected by ELISA. Autoantibodies were detected by indirect immunofluorescence and immunospot assay. We found that blood CXCR5+CD4+ T cells in patients with chronic HBV infection (HBV patients) expressed higher level of activation related molecules and cytokines than that from health controls (HC).In HBV patients, the frequency of blood CXCR5+CD4+ T cells was significantly correlated with serum ALT and AST. We also found that blood CXCR5+CD4+ T cells from HBV patients could induce B cells to secret higher level of immunoglobulin than that from HC. Several autoantibodies, including ANA, ss-A, ss-B, Scl-70, Jo-1, ect, were indeed positive in 65% HBV patients. Among HBV patients, expression of function related molecules was significantly higher in blood CXCR5+CD4+ T cells from patients with autoantibodies than that without autoantibodies. Our research indicated that blood CXCR5+CD4+ T cells from HBV patients were over activated and show augmented capacity to help B cells for antibody secreting, which might correlated with liver inflammation and the production of autoantibodies in extrahepatic manifestations. PMID:27612199

  10. The epidemiologic study: the serum levels of TSH, T4, T3 and autoantibodies in the Polish population

    International Nuclear Information System (INIS)

    In 1986-1990 epidemiologic studies on the thyroid diseased frequency in the Polish population were undertaken. During this studies the serum levels of TSH, T4, T3 and autoantibodies were estimated in more then 30 thousand people. TSH was estimated in 30749, T4 in 30928, T3 in 30621 and autoantibodies in 31265 randomly chosen people in 5 districts. We have arbitrarily established the normal range for TSH to be between 0.4-3.8 μIU/ml, for T4 4.4-12.5 μg and for T3 0.9-1.95 ng/ml. The tested group has been divide in 4 subgroup: girls and boys from 1 to 15 years of age of the Chernobyl accident, men and women from 15 to 50 years of age at the date of the accident. TSH values in the normal range were found in 85 to 92% of the tested population, depending on the subgroup. T4 vales in the normal range were found in 85 to 92% of the tested groups. T3 vales in the normal range were found in 86 to 93% of the tested groups. The absence on any kind of autoantibodies was established in 89.7% of the tested population. TSH values was above the normal range (above 3.8 μIU/ml) in 3.4% of boys, 4.3% girls, 3.2% men and 3.8% women. TSH vales below the normal range (less the 0.4 μIU/ml) were found in 4.3% boys, 5% girls, 10% men and 11.2% women. T4 values above the normal range (higher then 12.5 μg%) were found in 12.9% boys, 12.6% girls, 4.6% men and 5.9% women. T4 vales below the normal range (less then 4.4 μg%) were detected in 0.9% boys, 1.4% girls, 2.4% men and 2.0% women. T3 values higher then 1.95 ng/ml were found in 10.8% of boys, 11.5% girls, 2.6% men and 3.5% women. The percentage of values above of below the arbitrarily chosen normal range depends on the age and sex group. (author). 5 refs, 4 tabs

  11. IgM AUTOANTIBODIES TO DNA IN BLOOD SERUM OF THE PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

    Directory of Open Access Journals (Sweden)

    D. G. Ishmukhametova

    2010-01-01

    Full Text Available Levels of IgM autoantibodies (AAbs to native (double-stranded and denaturated (single-stranded DNA were studied in blood serum of sixty patients with hemorrhagic fever with renal syndrome (HFRS and twenty-five healthy persons, using an ELISA technique. The median levels of IgM AAbs to double-stranded DNA in blood serum of healthy persons and HFRS patients corresponded to 0.41 and 0.53 arbitrary units, respectively. Thus, the difference between the samples from HFRS and healthy persons proved to be non-significant. The median level of IgM AAbs to single-stranded DNA in blood sera of HFRS patients (0.71 arbitrary units did significantly exceed serum values of healthy persons (0.57 arbitrary units. A probable involvement of IgM AAbs into regulation of IgG AAbs' production during virus-induced activation of autoimmune events in HFRS patients is discussed.

  12. Results of the thyroid and diabetes-associated autoantibodies screening in children and adolescents living in various regions of Belarus

    International Nuclear Information System (INIS)

    Recently among the factors capable to induce autoimmune reaction, it is ionizing radiation that is discussed, along with virus infections and chemical influences. Investigation of 540 healthy children and adolescents (age range 12-19 y.o.) living in radionuclide contaminated areas (average cesium 137 contamination 0,19-0,56 MBq/m2) and in conditionally clear regions revealed significant differences in levels of diabetes-associated (AB-GAD, AB-IA2) and thyroid (AB-TG, AB-TPO) autoantibodies. At the same time frequencies of positive AB-IA2, AB-TPO and AB-TG were higher in persons from contaminated regions. Obtained results correlate with the increase of the type 1 diabetes incidence in children and adolescents from Gomel region and dictate the necessity to continue the such study

  13. C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production, and glomerulonephropathy in mice.

    Science.gov (United States)

    Atanasio, Amanda; Decman, Vilma; White, Derek; Ramos, Meg; Ikiz, Burcin; Lee, Hoi-Ching; Siao, Chia-Jen; Brydges, Susannah; LaRosa, Elizabeth; Bai, Yu; Fury, Wen; Burfeind, Patricia; Zamfirova, Ralica; Warshaw, Gregg; Orengo, Jamie; Oyejide, Adelekan; Fralish, Michael; Auerbach, Wojtek; Poueymirou, William; Freudenberg, Jan; Gong, Guochun; Zambrowicz, Brian; Valenzuela, David; Yancopoulos, George; Murphy, Andrew; Thurston, Gavin; Lai, Ka-Man Venus

    2016-01-01

    The expansion of a hexanucleotide (GGGGCC) repeat in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both the function of C9ORF72 and the mechanism by which the repeat expansion drives neuropathology are unknown. To examine whether C9ORF72 haploinsufficiency induces neurological disease, we created a C9orf72-deficient mouse line. Null mice developed a robust immune phenotype characterized by myeloid expansion, T cell activation, and increased plasma cells. Mice also presented with elevated autoantibodies and evidence of immune-mediated glomerulonephropathy. Collectively, our data suggest that C9orf72 regulates immune homeostasis and an autoimmune response reminiscent of systemic lupus erythematosus (SLE) occurs in its absence. We further imply that haploinsufficiency is unlikely to be the causative factor in C9ALS/FTD pathology. PMID:26979938

  14. Inhibitory axons are targeted in hippocampal cell culture by anti-Caspr2 autoantibodies associated with limbic encephalitis

    Directory of Open Access Journals (Sweden)

    Veronique Rogemond

    2015-07-01

    Full Text Available Contactin-associated protein-like 2 (Caspr2, also known as CNTNAP2, is a cell adhesion molecule that clusters voltage-gated potassium channels (Kv1.1/1.2 at the juxtaparanodes of myelinated axons and may regulate axonal excitability. As a component of the Kv1 complex, Caspr2 has been identified as a target in neuromyotonia and Morvan syndrome, but also in some cases of autoimmune limbic encephalitis. How anti-Caspr2 autoimmunity is linked with the central neurological symptoms is still elusive. In the present study, using anti-Caspr2 antibodies from seven patients affected by pure limbic encephalitis, we determined that IgGs in the cerebrospinal fluid of four out seven patients were selectively directed against the N-terminal Discoïdin and LamininG1 modules of Caspr2. Using live immunolabeling of cultured hippocampal neurons, we determined that serum IgGs in all patients strongly targeted inhibitory interneurons. Caspr2 was highly detected on GAD65-positive axons that are surrounding the cell bodies and at the VGAT-positive inhibitory presynaptic contacts. Functional assays indicated that LE autoantibodies may induce alteration of Gephyrin clusters at inhibitory synaptic contacts. Next, we generated a Caspr2-Fc chimera to reveal Caspr2 receptors on hippocampal neurons localized at the somato-dendritic compartment and post-synapse. Caspr2-Fc binding was strongly increased on TAG-1-transfected neurons and conversely, Caspr2-Fc did not bind hippocampal neurons from TAG-1-deficient mice. Our data indicate that Caspr2 may participate as a cell recognition molecule in the dynamics of inhibitory networks. This study provides new insight into the potential pathogenic effect of anti-Caspr2 autoantibodies in central hyperexcitability that may be related with perturbation of inhibitory interneuron activity.

  15. Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.

    Directory of Open Access Journals (Sweden)

    Shinji Ueno

    Full Text Available The paraneoplastic retinopathies (PRs are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1 protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice.

  16. Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals.

    Directory of Open Access Journals (Sweden)

    Karen I Maijer

    Full Text Available 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 synovial tissue of subjects at risk of RA.Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF and/or anti-citrullinated protein antibodies (ACPA, without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27. Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2; p = 0.020, also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5; p = 0.016. This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529 and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520 and ESR (leptin r = 0.512, chemerin r = 0.708, p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals.

  17. Development of an Aquaporin-4 Orthogonal Array of Particle-Based ELISA for Neuromyelitis Optica Autoantibodies Detection.

    Directory of Open Access Journals (Sweden)

    Francesco Pisani

    Full Text Available Serological markers of Nuromyelitis Optica (NMO, an autoimmune disorder of the central nervous system, are autoantibodies targeting the astrocytic water channel aquaporin-4 (AQP4. We have previously demonstrated that the main epitopes for these autoantibodies (AQP4-IgG are generated by the supramolecular arrangement of AQP4 tetramers into an Orthogonal Array of Particles (OAPs. Many tests have been developed to detect AQP4-IgG in patient sera but several procedural issues affect OAP assembly and consequently test sensitivity. To date, the protein based ELISA test shows the lowest sensitivity while representing a valid alternative to the more sensitive cell based assay (CBA, which, however, shows economic, technical and interpretation problems. Here we have developed a high perfomance ELISA in which native OAPs are used as the molecular target. To this aim a native size exclusion chromatography method has been developed to isolate integral, highly pure and AQP4-IgG-recognized OAPs from rat brain. These OAPs were immobilized and oriented on a plastic plate by a sandwich approach and 139 human sera were tested, including 67 sera from NMO patients. The OAP-ELISA showed a 99% specificity and a higher sensitivity (91% compared to the CBA test. A comparative analysis revealed an end-point titer three orders of magnitude higher than the commercial ELISA and six times higher than our in-house CBA test. We show that CNS-extracted OAPs are crucial elements in order to perform an efficient AQP4-IgG test and the OAP-ELISA developed represents a valid alternative to the CBA currently used.

  18. The diagnostic value of Th1/Th2 cell cytokine and thyroid autoantibody on autoimmune thyroid diseases

    International Nuclear Information System (INIS)

    To study the diagnostic value of Th1/Th2 cell cytokine and thyroid autoantibody in autoimmune thyroid diseases (AITD), 28 patients with Graves' disease (GD), 15 patients with hyperthyroidism and thyroiditis (GDIII), 13 patients with Hashimoto's hyperthyroidism (HTL), 21 patients with Hashimoto's thyroiditis(HT)and 20 healthy subjects were enrolled in this study. The serum concentrations of Th1 cytokine (IFN-γ) and Th2 cytokine (IL-4) were determined by ELISA. The serum levels of thyrotropin receptor antibodies (TRAb), thyroglobulin antibodies (TGAb) and thyroid peroxidase antibodies (TPOAb) were measured by RIA. The relationship between the serum levels of IFN-γ, IL-4 and TRAb, TGAb and TPOAb were analyzed. The results showed that IFN-γ levels from higher to lower in different groups were in the order of HT, HTL, GDIII, GD and the IL-4 were GD, GDIII, HTL, HT, respectively. There was significant difference in the IFN-γ (P<0.05) and IL-4 levels (P<0.01) between GDIII and HTL groups. There was no significant difference in TGAb and TPOAb between GDIII and HTL groups. In HT group, IFN-γ levels was positively correlated with TGAb and TPOAb (r=0.67,0.54,P<0.01). In GD group, IL-4 was positively correlated with TRAb (r =0.71,P<0.01). The imbalance of Th1/Th2 cell cytokine reflects pathologic change and abnormality of immune function in AITD patients. The detection of Th1/Th2 cell cytokine combined with thyroid autoantibody may be regarded as an indicator in the diagnosis of autoimmune thyroid diseases. (authors)

  19. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-glomerular basement membrane autoantibodies specific for α345NC1 hexamers.

    Science.gov (United States)

    Olaru, Florina; Wang, Xu-Ping; Luo, Wentian; Ge, Linna; Miner, Jeffrey H; Kleinau, Sandra; Geiger, Xochiquetzal J; Wasiluk, Andrew; Heidet, Laurence; Kitching, A Richard; Borza, Dorin-Bogdan

    2013-02-15

    Goodpasture disease is an autoimmune kidney disease mediated by autoantibodies against noncollagenous domain 1 (NC1) monomers of α3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis (GN). We identified a novel type of human IgG4-restricted anti-GBM autoantibodies associated with mild nonprogressive GN, which specifically targeted α345NC1 hexamers but not α3NC1 monomers. The mechanisms eliciting these anti-GBM autoantibodies were investigated in mouse models recapitulating this phenotype. Wild-type and FcγRIIB(-/-) mice immunized with autologous murine GBM NC1 hexamers produced mouse IgG1-restricted autoantibodies specific for α345NC1 hexamers, which bound to the GBM in vivo but did not cause GN. In these mice, intact collagen IV from murine GBM was not immunogenic. However, in Col4a3(-/-) Alport mice, both intact collagen IV and NC1 hexamers from murine GBM elicited IgG Abs specific for α345NC1 hexamers, which were not subclass restricted. As heterologous Ag in COL4A3-humanized mice, murine GBM NC1 hexamers elicited mouse IgG1, IgG2a, and IgG2b autoantibodies specific for α345NC1 hexamers and induced anti-GBM Ab GN. These findings indicate that tolerance toward autologous intact α345(IV) collagen is established in hosts expressing this Ag, even though autoreactive B cells specific for α345NC1 hexamers are not purged from their repertoire. Proteolysis selectively breaches this tolerance by generating autoimmunogenic α345NC1 hexamers. This provides a mechanism eliciting autoantibodies specific for α345NC1 hexamers, which are restricted to noninflammatory IgG subclasses and are nonnephritogenic. In Alport syndrome, lack of tolerance toward α345(IV) collagen promotes production of alloantibodies to α345NC1 hexamers, including proinflammatory IgG subclasses that mediate posttransplant anti-GBM nephritis. PMID:23303673

  20. 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

  1. Anticorpos antiproteínas citrulinadas e a artrite reumatóide Auto-antibodies to citrullinated proteins and rheumatoid arthritis

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    Renata Trigueirinho Alarcon

    2007-06-01

    Full Text Available Pacientes com artrite reumatóide (AR possuem uma variedade de auto-anticorpos no soro e no líquido sinovial. Entre esses auto-anticorpos, destacam-se aqueles direcionados a proteínas citrulinadas, que são específicos para AR, aparecem precocemente durante a evolução da enfermidade e são bastante úteis para auxiliar no diag-nóstico da doença. Entre os antígenos citrulinados reconhecidos por auto-anticorpos na AR, encontram-se a profilagrina, a filagrina e a vimentina. Células e tecidos ricos nessas proteínas serviram de substrato para os primeiros ensaios laboratoriais para detecção dessa classe de auto-anticorpos. A descoberta de que os epitopos reconhecidos por esses auto-anticorpos eram peptídeos contendo citrulina permitiu o desenvolvimento de uma plataforma baseada em ELISA. O formato de ELISA possibilitou maior padronização e reprodutibilidade dos ensaios, resultando em ampla aceitação mundial como os auto-anticorpos mais específicos e precoces para o diagnóstico da AR. Há controvérsia quanto à capacidade dos anticorpos contra proteínas citrulinadas predizerem a gravidade da doença. O papel dos antígenos citrulinados na fisiopatologia da artrite reumatóide é sugerido pela forte especificidade desses auto-anticorpos para a doença, pelo achado de proteínas citrulinadas na sinóvia inflamada, pela produção intra-articular desses auto-anticorpos e pela extrema afinidade de peptídeos citrulinados por moléculas de HLA-DRB1 que contêm o epitopo compartilhado. Esses achados acenam com a possibilidade de novas e fascinantes descobertas rumo à melhor compreensão da fisiopatologia da AR.Rheumatoid arthritis (RA patients have a variety of auto-antibodies in the serum and synovial fluid. Among these auto-antibodies, those directed against citrullinated proteins are distinguished because that are specific for RA, appear early during the evolution of the disease and they are important to assist in the diagnosis of

  2. Rapid Normalization of High Glutamic Acid Decarboxylase Autoantibody Titers and Preserved Endogenous Insulin Secretion in a Patient with Diabetes Mellitus: A Case Report and Literature Review.

    Science.gov (United States)

    Ohara, Nobumasa; Kaneko, Masanori; Furukawa, Tatsuo; Koike, Tadashi; Sone, Hirohito; Tanaka, Shoichiro; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 59-year-old Japanese woman developed diabetes mellitus without ketoacidosis in the presence of glutamic acid decarboxylase autoantibody (GADA) (24.7 U/mL). After the amelioration of her hyperglycemia, the patient had a relatively preserved serum C-peptide level. Her endogenous insulin secretion capacity remained almost unchanged during 5 years of insulin therapy. The patient's GADA titers normalized within 15 months. The islet-related autoantibodies, including GADA, are believed to be produced following the autoimmune destruction of pancreatic beta cells and are predictive markers of type 1 diabetes mellitus. Therefore, the transient appearance of GADA in our patient may have reflected pancreatic autoimmune processes that terminated without progression to insulin deficiency. PMID:26935368

  3. Anti-β2 glycoprotein I (β2GPI) autoantibodies recognize an epitope on the first domain of β2GPI

    OpenAIRE

    Iverson, G. Michael; Victoria, Edward J.; Marquis, David M.

    1998-01-01

    Anticardiolipin (aCL) autoantibodies are associated with thrombosis, recurrent fetal loss, and thrombocytopenia. Only aCL found in autoimmune disease require the participation of the phospholipid binding plasma protein β2 glycoprotein I (β2GPI) for antibody binding and now are called anti-β2GPI. The antigenic specificity of aCL affinity purified from 11 patients with high titers was evaluated in an effort to better understand the pathophysiology associated with aCL. Seven different recombinan...

  4. Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease in girls and women with Turner syndrome

    Directory of Open Access Journals (Sweden)

    Kämpe Olle

    2007-12-01

    Full Text Available Abstract Background A disturbance in the immune system has been described in Turner syndrome (45,X, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X, thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency ear problems are common. Otitis media and a progressive sensorineural hearing disorder are commonly seen. In the normal population there are known inner ear disorders related to autoimmune diseases. The aim of this study was to investigate patients with Turner syndrome regarding autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine syndrome type I and II and Addison's disease, to screen for overlapping profile of autoantibodies. Blood samples from 110 Turner patients (7–65 years were investigated using in vitro transcription, translation and immunoprecipitation techniques regarding autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease (21-hydroxylase, 17α-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, tyrosine hydroxylase and tryptophan hydroxylase. Results The autoantibodies investigated were not overrepresented among the Turner patients. Conclusion The autoimmune disorders associated with Turner syndrome do not seem to be of the same origin as Addison's disease, the type I or II autoimmune polyendocrine syndrome.

  5. Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study

    OpenAIRE

    Raab, Jennifer; Haupt, Florian; Scholz, Marlon; Matzke, Claudia; Warncke, Katharina; Lange, Karin; Assfalg, Robin; Weininger, Katharina; Wittich, Susanne; Löbner, Stephanie; Beyerlein, Andreas; Nennstiel-Ratzel, Uta; Lang, Martin; Laub, Otto; Dunstheimer, Desiree

    2016-01-01

    Introduction Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care. Methods and analysis Children aged 2–5 years in Bavaria, Germany, will be teste...

  6. Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

    OpenAIRE

    Jing Li; Xiaomei Leng; Zhijun Li; Zhizhong Ye; Caifeng Li; Xiaofeng Li; Ping Zhu; Zhengang Wang; Yi Zheng; Xiangpei Li; Miaojia Zhang; Xin-Ping Tian; Mengtao Li; Jiuliang Zhao; Feng-Chun Zhang

    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 (P < 0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and ne...

  7. The Thomsen-Friedenreich antigen-binding lectin jacalin interacts with desmoglein-1 and abrogates the pathogenicity of pemphigus foliaceus autoantibodies in vivo.

    Science.gov (United States)

    Li, Ning; Park, Moonhee; Zhao, Minglang; Hilario-Vargas, Julio; McInnes, David M; Prisayanh, Phillip S; Liu, Zhi; Diaz, Luis A

    2010-12-01

    Pemphigus foliaceus (PF) is an autoimmune skin blistering disease mediated by pathogenic autoantibodies against the desmosomal core glycoprotein desmoglein-1 (Dsg1). This study demonstrated that the O-glycan-specific plant lectin jacalin binds Dsg1 and inhibits the interaction of Dsg1/PF IgG. N-glycosylation is not involved in the interaction of Dsg1/jacalin or Dsg1/PF IgG. Subcutaneous injection of jacalin into neonatal mice drastically reduced PF IgG deposition at the epidermal cell surface and blocked PF IgG-induced skin blisters, both clinically and histologically. Interestingly, another plant lectin, peanut agglutinin, which shares the same carbohydrate specificity toward the O-linked carbohydrate structure known as Thomsen-Friedenreich antigen (TF antigen, Galβ1-3GalNAcα-O-Ser/Thr), also bound Dsg1 and blocked the skin blistering. In contrast, the plant lectin vicia villosa-B4 (VVL-B4), which shares the carbohydrate specificity toward the O-linked monosaccharide known as Thomsen-nouveau antigen (GalNAc-α1-O-Ser/Thr), did not bind Dsg1 and did not show a protective effect against the disease induced by the autoantibodies. Collectively, these results suggest that the binding of jacalin to O-linked TF carbohydrate motifs on Dsg1 impairs the Dsg1/PF autoantibody interactions and abrogates its pathogenicity in vivo. TF-specific binding ligands may have a potential therapeutic value for PF. PMID:20631728

  8. Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Jing Li

    2014-01-01

    Full Text Available 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 (P<0.05 associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH; between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P<0.05. Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P<0.05. Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations 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.

  9. The presence of non-organ-specific autoantibodies is associated with a negative response to combination therapy with interferon and ribavirin for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Matern Siegfried

    2004-02-01

    Full Text Available Abstract Background Non-organ-specific autoantibodies are found in a considerable number of anti-HCV positive patients. Previous studies investigated the clinical relevance of these antibodies in patients treated with interferon monotherapy, but not combination therapies. Methods Anti-nuclear, anti-smooth muscle, anti-mitochondrial, anti-neutrophil-cytoplasmatic and anti-liver/kidney microsomal antibodies were determined in 78 consecutive anti-HCV positive patients by indirect immunofluorescence. The presence of these antibodies was related to demographic variables and to the outcome of antiviral combination therapy with interferon-α and ribavirin in 65 patients. Results In our study, positivity for autoantibodies was associated with higher alanine aminotransferase levels and higher mean values for HCV-RNA (p Conclusions The absence of non-organ-specific autoantibodies might indicate a significantly higher chance for viral clearance in response to combination therapy for chronic hepatitis C infection. Therefore, despite of an overall higher treatment response, the addition of the immunomodulatory drug ribavirin could accentuate immunological differences that affect treatment outcome and might have been less obvious in earlier studies analysing interferon monotherapy.

  10. Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production

    Science.gov (United States)

    Looger, Loren L.; Han, Shizhong; Kim-Howard, Xana; Glenn, Stuart; Adler, Adam; Kelly, Jennifer A.; Niewold, Timothy B.; Gilkeson, Gary S.; Brown, Elizabeth E.; Alarcón, Graciela S.; Edberg, Jeffrey C.; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; Freedman, Barry I.; Tsao, Betty P.; Criswell, Lindsey A.; Jacob, Chaim O.; Moore, Jason H.; Vyse, Timothy J.; Langefeld, Carl L.; Guthridge, Joel M.; Gaffney, Patrick M.; Moser, Kathy L.; Scofield, R. Hal; Alarcón-Riquelme, Marta E.; Williams, Scott M.; Merrill, Joan T.; James, Judith A.; Kaufman, Kenneth M.; Kimberly, Robert P.; Harley, John B.; Nath, Swapan K.

    2013-01-01

    Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22–24 (LOD = 6.28), and the admixture signal is associated with the European ancestry (ancestry risk ratio ∼1.5). Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [Pmeta = 5.20×10−14; odds ratio, 95% confidence interval = 0.82 (0.78–0.87)], and two missense variants, rs1990760 (Ala946Thr) [Pmeta = 3.08×10−7; 0.88 (0.84–0.93)] and rs10930046 (Arg460His) [Pdom = 1.16×10−8; 0.70 (0.62–0.79)]. Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis. PMID

  11. HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc Patients.

    Directory of Open Access Journals (Sweden)

    Tatiana S Rodriguez-Reyna

    Full Text Available Human leukocyte antigen (HLA polymorphism studies in Systemic Sclerosis (SSc have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications.We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population.Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02, and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients.This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as

  12. Evaluation of the BioPlex 2200 ANA screen: analysis of 510 healthy subjects: incidence of natural/predictive autoantibodies.

    Science.gov (United States)

    Shovman, O; Gilburd, B; Barzilai, O; Shinar, E; Larida, B; Zandman-Goddard, G; Binder, S R; Shoenfeld, Y

    2005-06-01

    The BioPlex 2200 ANA Screen is a fully automated system that determines levels for 13 different autoimmune antibodies of established clinical significance. The objective of this study was to determine the specificity of the BioPlex 2200 ANA Screen assay and to analyze the antibody profile samples collected from healthy subjects against comparative ELISA and IIF screening methods. A total of 510 specimens were randomly selected from a cohort of apparently healthy blood bank donors. Samples were distributed to five age brackets. All samples were tested using Bio-Rad's ANA Screen kit. Specificity was compared to IIF and ELISA results. Most of the samples were found negative in all ANA screening systems (84.5% by IIF, 92.5% by BioPlex 2200 ANA Screen kit, and 94.5% by ELISA). The frequency of positive results was highest (15.5%) using IIF, in comparison to almost similar results (5.5% vs. 7.5%) achieved by ANA ELISA and BioPlex 2200 ANA Screen kits. The positive rate of autoantibodies was significantly reduced when analyzed by different combinations of ANA screen assays (from 2.35% using IIF + BioPlex ANA Screen tests to 0.98% by using all three tests). Using the BioPlex 2200 ANA Screen system, we were able to identify samples with high levels of individual antibodies: anti-dsDNA at 20-63 IU/mL, antichromatin at 4-8 AI, anti-SmRNP at 2-6 AI, and anti-RNPA at 2-4.5 AI. Importantly, from 7 IIF and ELISA positive sera, 5 of these were also BioPlex 2200 positive, suggesting that the BioPlex is seeing the samples that are of the greatest interest, using the established techniques. The specificity of the BioPlex 2200 ANA Screen analysis of 13 different analytes (dsDNA, centromere B, chromatin, Jo1, ribosomal P, RNP 68, RNP A, Scl-70, Sm, SmPNP, SS-A52, SS-A60, SS-B) is comparable (P < 0.252) to the ELISA ANA screening test. Like the ELISA, the BioPlex 2200 has a lower (P < 0.001) positive rate than IIF for the autoantibody screening. PMID:16014555

  13. Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production.

    Directory of Open Access Journals (Sweden)

    Julio E Molineros

    Full Text Available Systemic lupus erythematosus (SLE is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA. Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD=6.28, and the admixture signal is associated with the European ancestry (ancestry risk ratio ~1.5. Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P(meta = 5.20×10(-14; odds ratio, 95% confidence interval = 0.82 (0.78-0.87], and two missense variants, rs1990760 (Ala946Thr [P(meta = 3.08×10(-7; 0.88 (0.84-0.93] and rs10930046 (Arg460His [P(dom = 1.16×10(-8; 0.70 (0.62-0.79]. Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis.

  14. HCV感染者自身抗体对肝脏损伤的影响%The impact of autoantibodies on liver histology in hepatitis C

    Institute of Scientific and Technical Information of China (English)

    李文淑; 赵景民; 周光德; 刘树红; 郭晓东; 杨建法; 赵雨来

    2011-01-01

    目的 分析血清自身抗体阳性慢性HCV感染者肝脏详细病理改变,探讨慢性HCV感染者血清自身抗体与肝脏损伤的关系.方法 采用间接免疫荧光法测定血清抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA)、抗肝肾微粒体抗体(LKM)、抗胃壁细胞抗体(PCA).采用荧光定量PCR测定HCV RNA载量、HCV基因型,同时检测肝功指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、碱性磷酸酶(ALP)、γ-谷氨酰基转移酶(GGT).依据Ishak病理评价方案对肝活检组织炎症活动度和纤维化程度进行总体评分和详细组织病理评价.结果 15例(23.81%)慢性HCV感染者自身抗体阳性,其中ANA阳性9例(14.29%)、SMA 阳性2例(3.17%)、AMA 阳性3例(4.76%)、PCA阳性2例(3.17%),包括ANA、SMA双阳性1例.自身抗体阳性HCV感染者年龄显著大于自身抗体阴性HCV感染者[(44.80±9.61)岁VS.(34.04±13.18)岁,P=0.005],自身抗体阳性HCV感染者血清ALT、AST、GGT水平显著升高,肝脏炎症活动度评分显著高于自身抗体阴性HCV感染者,其中融合坏死和点灶状坏死较重,未见其他临床指标和组织学差异.结论 HCV 感染者血清自身抗体会导致以融合坏死和点灶状坏死加重为主的肝脏组织学病变.%Objective To evaluate the detailed pathological changes in liver tissues of autoantibody -positive patients with chronic hepatitis C virus ( HCV) infection and to explore the association between autoantibodies and liver injury of chronic HCV infection . Methods A retrospective study was performed based on a total of 63 patients with chronic HCV infection. Autoantibodies were detected in all the patients , including antinuclear antibody (ANA) , anti-smooth muscle antibody ( SMA ) , anti-mitochondrial antibody (AMA) , anti-liver/kidney microsomal antibody (LKM) and parietal cell autoantibody (PCA) ,using indirect immunofluorescence assay. HCV

  15. Smoking, disease activity, permanent damage and dsDNA autoantibody production in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Ekblom-Kullberg, Susanne; Kautiainen, Hannu; Alha, Pirkko; Leirisalo-Repo, Marjatta; Miettinen, Aaro; Julkunen, Heikki

    2014-03-01

    The aim was to study the association of smoking with the activity and severity of systemic lupus erythematosus (SLE) and the production of antibodies to dsDNA. The study included 223 SLE patients attending the outpatient clinics at Helsinki University Central Hospital. The history of smoking was obtained by personal interview, and clinical data related to SLE by interview, clinical examination and chart review. The activity of SLE was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score and permanent damage by the SLICC/ACR score. Antibodies to dsDNA were determined by three ELISA assays, by the indirect immunofluorescence technique using Crithidia luciliae cells as substrates and by the Farr assay. There were no significant differences in the SLEDAI scores between current smokers (73 patients), ex-smokers (59) and never-smokers (91), though current smokers tended to have lower disease activity. The SLICC/ACR scores between the groups were practically equal. Current smokers had significantly lower levels of antibodies to dsDNA than ex- and never-smokers (p = 0.025). Our study suggests that cigarette smoke may have immunosuppressive effect on autoantibody production in patients with SLE. Permanent damage was not found to be associated with smoking. PMID:24170320

  16. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies.

    Science.gov (United States)

    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 systems have been developed during the last decade. In addition, solid phase immunoassays using well characterized antigens have gained widespread adoption in high throughput laboratories due to their ease of use and open automation. Despite all the advances in the field of ANA detection and its contribution to the diagnosis of SARD, significant challenges persist. This review provides a comprehensive overview of the current status on ANA testing including automated IIF reading systems and solid phase assays and suggests an approach to interpretation of results and discusses meeting the problems of assay standardization and other persistent challenges. PMID:24868563

  17. Methimazole, but not betamethasone, prevents 131I treatment-induced rises in thyrotropin receptor autoantibodies in hyperthyroid Graves' disease

    International Nuclear Information System (INIS)

    The effects of methimazole or betamethasone therapy on the TSH receptor antibody response to radioiodine therapy were compared in a prospective randomized study of 60 patients with hyperthyroidism due to Graves' disease. The patients were followed for 1 yr after treatment with 131I. Twenty-three patients received 131I alone, 17 were treated with methimazole for 2 months before and 3 months after 131I therapy, and 20 patients were treated with betamethasone for 3 weeks before and 4 weeks after 131I therapy. 131I induced a transient rise in the mean serum level of TSH receptor autoantibodies, measured as TSH binding inhibitory immunoglobulin (TBII), but in patients receiving methimazole treatment, no such rise occurred. In the betamethasone-treated patients, TBII increased similarly to that in patients treated with 131I alone. In addition, in patients given betamethasone, there was an early decrease in total serum immunoglobulin G, which persisted throughout the follow-up period. In the other 2 groups, no changes in total immunoglobulin G were found. The results demonstrate that in hyperthyroid Graves' disease, TBII production is influenced by therapy. Methimazole abolished the 131I-induced increase in TBII, whereas betamethasone did not have such an inhibitory effect

  18. Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study.

    Science.gov (United States)

    Kampmann, E; Diana, T; Kanitz, M; Hoppe, D; Kahaly, G J

    2015-01-01

    The clinical utility of the functional TSH receptor autoantibodies was prospectively evaluated in patients with thyroid-associated orbitopathy (TAO). Ophthalmic, endocrine, and serological investigations were performed in 101 consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb) and blocking (TBAb) antibody levels were measured with two bioassays using cells that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results are expressed as percentage of specimen-to-reference ratio (SRR %). Blocking activity is defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone. All 101 consecutively followed-up patients with severe and active TAO were TBAb negative. In contrast, 91 (90%) were TSAb positive of whom 90 had Graves' disease. Serum TSAb levels correlated with the diplopia score (P = 0.016), total severity eye score (P = 0.009), proptosis (P = 0.007), lid aperture (P = 0.003), upper lid retraction (P = 0.006), keratopathy (P = 0.04), and thyroid binding inhibiting immunoglobulins (TBII, P < 0.001) and negatively with the duration of TAO (P = 0.002). Median serum values of TSAb were SRR% 418 (range 28% to 795%). TSAb, not TBAb, are highly prevalent in severe/active TAO and serum TSAb levels correlate with clinical disease severity. PMID:26221139

  19. Aptamer binding and neutralization of β1-adrenoceptor autoantibodies: basics and a vision of its future in cardiomyopathy treatment.

    Science.gov (United States)

    Haberland, Annekathrin; Wallukat, Gerd; Schimke, Ingolf

    2011-08-01

    Autoantibodies directed against the second extracellular receptor loop of the β(1) receptor (β(1)-ECII-AABs) that belong to the superfamily of G protein-coupled receptors have been frequently found in patients with idiopathic dilated cardiomyopathy, Chagas' cardiomyopathy, and peripartum cardiomyopathy and have been clearly evidenced to be related to disease pathogenesis. Consequently, specific proteins or peptides used as binders in immunoapheresis or as in vivo neutralizers of β(1)-ECII-AABs have been suggested for patient treatment. Aptamers, which are target specifically selected short single- or double-stranded RNA or DNA sequences, are a recently introduced new molecule class applicable to bind and neutralize diverse molecule species, including antibodies. This article reviews selection technologies and characteristics of aptamers with respect to a single-stranded DNA aptamer recently identified as having a very high affinity against β(1)-ECII-AABs. The potential of this aptamer for the elimination of β(1)-ECII-AABs and in vivo neutralization is critically analyzed in view of its potential for future use in cardiomyopathy treatment. PMID:22814426

  20. Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages

    International Nuclear Information System (INIS)

    Asbestos exposure is associated with increased autoimmune responses in humans. For example, in Libby, MT where significant asbestos exposure has occurred due to an asbestos-contaminated vermiculite mine near the community, residents have developed increased autoimmune responses compared to an unexposed population. However, the exact mechanism by which Libby amphibole asbestos generates autoimmune responses is unclear. A murine model of amphibole asbestos-induced autoimmunity was recently established, and one of the targets of the autoantibodies (AAs) was the SSA/Ro52 autoantigen. The purpose of this study was to determine whether the SSA/Ro52 autoantigen is exposed at the surface of cells as a result of asbestos exposure as a possible mechanism leading to antigenicity. Our results indicate that Libby asbestos induces apoptosis in murine macrophages as determined by phosphatidylserine exposure, cleavage of poly(ADP-ribose) polymerase and morphological changes such as nuclear condensation. Moreover, asbestos-induced apoptosis results in the formation of apoptotic cell surface blebs enriched in SSA/Ro52 as determined by confocal microscopy. Most importantly, apoptotic cell surface blebs are recognized by AAs from mice exposed to amphibole asbestos suggesting that these cell surface structures may be antigenic when presented in a pro-inflammatory context. This study supports the hypothesis that the induction of apoptosis plays a key role in environmentally induced autoimmunity through cell surface exposure of a known autoantigen

  1. No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

    Science.gov (United States)

    Mahabir, S; Baer, D J; Johnson, L L; Frenkel, K; Dorgan, J F; Cambell, W; Hartman, T J; Clevidence, B; Albanes, D; Judd, J T; Taylor, P R

    2005-08-01

    Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used. PMID:16030435

  2. Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease.

    Science.gov (United States)

    Flach, Anne-Christine; Litke, Tanja; Strauss, Judith; Haberl, Michael; Gómez, César Cordero; Reindl, Markus; Saiz, Albert; Fehling, Hans-Jörg; Wienands, Jürgen; Odoardi, Francesca; Lühder, Fred; Flügel, Alexander

    2016-03-22

    Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue. PMID:26957602

  3. 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

    surveys. In the present study we evaluated if TPO-Ab and Tg-Ab tend to develop in parallel or whether one or the other may be more prevalent in subsets of the population. METHODS In a cross-sectional comparative study, performed in two areas of Denmark with mild and moderate iodine deficiency, 4649...... randomly selected subjects in age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the radioimmunoassay (RIA) technique. The participants answered questionnaires, were clinically examined and had urine samples collected. RESULTS The overall...... 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...

  4. Use of the VH6-1 gene segment to code for anti-interleukin-18 autoantibodies in multiple sclerosis.

    Science.gov (United States)

    Tiumentseva, Marina; Morozova, Vera; Zakabunin, Aleksandr; Korobko, Denis; Malkova, Nadezhda; Filipenko, Maksim; Tikunova, Nina

    2016-04-01

    We investigated whether levels and repertoires of anti-interleukin-18 (IL-18) autoantibodies (auto-Abs) differ in multiple sclerosis (MS) patients and healthy donors (HDs). IL-18 concentration in MS patients' sera was higher than in HD, but the level of anti-IL-18 auto-Abs was lower in MS patients. Correlation patterns of IL-18/anti-IL-18 auto-Abs system differed in HD and MS patients, so we have compared segment composition of the anti-IL-18 single-chain variable fragments (scFvs) selected from MS and naïve phage display libraries. Considerable differences between anti-IL-18 auto-Abs of these libraries were found. MS panel contained auto-Abs displaying both signs of "fetal" and somatically hypermutated repertoires. Naïve panel mainly contained the naïve antibodies. These variations from the norm are possible results of abnormal regulation of the repertoire perhaps determined by remodeling of the molecular mechanisms involved in the V(D)J recombination and/or abnormal selection by antigen in MS pathogenesis. PMID:26743536

  5. The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection.

    Science.gov (United States)

    Dieudé, Mélanie; Bell, Christina; Turgeon, Julie; Beillevaire, Deborah; Pomerleau, Luc; Yang, Bing; Hamelin, Katia; Qi, Shijie; Pallet, Nicolas; Béland, Chanel; Dhahri, Wahiba; Cailhier, Jean-François; Rousseau, Matthieu; Duchez, Anne-Claire; Lévesque, Tania; Lau, Arthur; Rondeau, Christiane; Gingras, Diane; Muruve, Danie; Rivard, Alain; Cardinal, Héloise; Perreault, Claude; Desjardins, Michel; Boilard, Éric; Thibault, Pierre; Hébert, Marie-Josée

    2015-12-16

    Autoantibodies to components of apoptotic cells, such as anti-perlecan antibodies, contribute to rejection in organ transplant recipients. However, mechanisms of immunization to apoptotic components remain largely uncharacterized. We used large-scale proteomics, with validation by electron microscopy and biochemical methods, to compare the protein profiles of apoptotic bodies and apoptotic exosome-like vesicles, smaller extracellular vesicles released by endothelial cells downstream of caspase-3 activation. We identified apoptotic exosome-like vesicles as a central trigger for production of anti-perlecan antibodies and acceleration of rejection. Unlike apoptotic bodies, apoptotic exosome-like vesicles triggered the production of anti-perlecan antibodies in naïve mice and enhanced anti-perlecan antibody production and allograft inflammation in mice transplanted with an MHC (major histocompatibility complex)-incompatible aortic graft. The 20S proteasome core was active within apoptotic exosome-like vesicles and controlled their immunogenic activity. Finally, we showed that proteasome activity in circulating exosome-like vesicles increased after vascular injury in mice. These findings open new avenues for predicting and controlling maladaptive humoral responses to apoptotic cell components that enhance the risk of rejection after transplantation. PMID:26676607

  6. Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies

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    Michael Mahler

    2014-01-01

    Full Text Available 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 systems have been developed during the last decade. In addition, solid phase immunoassays using well characterized antigens have gained widespread adoption in high throughput laboratories due to their ease of use and open automation. Despite all the advances in the field of ANA detection and its contribution to the diagnosis of SARD, significant challenges persist. This review provides a comprehensive overview of the current status on ANA testing including automated IIF reading systems and solid phase assays and suggests an approach to interpretation of results and discusses meeting the problems of assay standardization and other persistent challenges.

  7. Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo.

    Science.gov (United States)

    Németh, Tamás; Futosi, Krisztina; Sitaru, Cassian; Ruland, Jürgen; Mócsai, Attila

    2016-01-01

    Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and dermatitis in mice. Neutrophil-specific deletion of CARD9 is sufficient to induce that phenotype. Card9(-/-) neutrophils show defective immune complex-induced gene expression changes and pro-inflammatory chemokine/cytokine release but normal LTB4 production and other short-term responses. In vivo deletion of CARD9 reduces tissue levels of pro-inflammatory chemokines and cytokines but not LTB4. The CARD9-mediated signalling pathway involves Src-family kinases, Syk, PLCγ2, Bcl10/Malt1 and NFκB. Collectively, CARD9-mediated gene expression changes within neutrophils play important roles during non-infectious inflammation in vivo and CARD9 acts as a divergence point between chemokine/cytokine and lipid mediator release. PMID:27032818

  8. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

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    Mark A Little

    Full Text Available Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3 antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener's granulomatosis. Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17% more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

  9. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

    LENUS (Irish Health Repository)

    Little, Mark A

    2012-01-01

    Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3) antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener\\'s granulomatosis). Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻\\/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17%) more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

  10. Detection of Autoantibodies against Recombinant Desmoglein 1 and 3 Molecules in Patients with Pemphigus vulgaris: Correlation with Disease Extent at the Time of Diagnosis and during Follow-Up

    Directory of Open Access Journals (Sweden)

    Anna Belloni-Fortina

    2009-01-01

    Full Text Available The recent availability of cDNA clones for pemphigus antigens has allowed the production of recombinant desmoglein 1 and desmoglein 3 molecules and the development of an ELISA approach in order to determine levels of antibodies to them. The aim of the study was to determine the relationship between autoantibodies levels and the extent of both mucosal and skin lesions in 20 patients with pemphigus vulgaris at the time of diagnosis and during follow-up. For the detection of autoantibodies by ELISA we used the recombinant proteins expressing overlapping sequences with the entire extracellular desmoglein 1 and desmoglein 3 domains. We showed that in presence of mucosal lesions there was a correlation between extension of mucosal involvement and autoantiboidies titres against both desmoglein 1 and desmoglein 3, whereas in presence of skin lesions there was a statistically significant correlation between extension of skin lesions and autoantibodies titres against desmoglein 3, but not against desmoglein 1. A not negligible number of patients showed variations of the desmoglein 3 autoantibodies titre which did not correlate with the severity of both cutaneous and mucosal involvement. Similar results were obtained analyzing autoantibodies titres against desmoglein 1. In conclusion, we believe that the utilization of recombinant desmoglein 1 and desmoglein 3 proteins by ELISA should be used with caution to monitor disease severity and response to therapy, although it remains a high specific test for the initial diagnosis of pemphigus and the identification of a change in the clinical phenotype of this condition.

  11. AN ASSOCIATION OF CYTOKINE LEVELS WITH DISEASE ACTIVITY, AUTOANTIBODY LEVELS, AND JOINT DESTRUCTIVE CHANGES IN EARLY RHEUMATOID ARTHRITIS

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    A. S. Avdeeva

    2015-09-01

    Full Text Available Objective: to assess the association of cytokine profile measures with disease activity, autoantibody levels, and joint destructive changes in patients with early rheumatoid arthritis (RA.Subjects and methods. Forty-five patients, including 35 women, with early RA were examined. Their median age was 53.5 [46; 59.5] years; the duration of the disease – 7.0 [4.0; 11.5] months; DAS28 – 5.8 [4.9; 6.4]; 91 and 96% of the patents were positive for rheumatoid factor (RF and anticyclic citrullinated peptide antibodies, respectively. Serum cytokine concentrations were estimated using the xMAP multiplex technology. The modified Sharp method was employed to quantify radiographic changes.Results and discussion. A group of 30 patients with high disease activity (DAS28 >5.1 had higher levels of interleukin (IL-6 (62.3 [36.1; 127.5] pg/ml and IP-10 (6367.8 [3682.7; 10691.3] pg/ml than 15 patients with moderate/low disease activity (DAS28 ≤5.1 (35.8 [13.4; 64.2] and 3222.6 [1881.0; 5671.9] pg/ml, respectively, p < 0.05. The patients highly positive for IgM RF had higher levels (pg/ml of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-12, IL-15, interferon-γ, and tumor necrosis factor-α; the chemokine monocyte chemotactic protein-1 and the growth factors IL-7 and vascular endothelial growth factor (4.8 [2.8; 19.3], 23.0 [7.1; 55.8], 64.2 [41.6; 170.5], 52.2 [30.9; 126.9], 2.4 [0.2; 11.2], 210.8 [119.9; 584.2], 90.7 [42.7; 307/9], 57.5 [26.1; 93.8], 54.9 [37.1; 123.7], and 143.3 [70.6; 249.6] pg/ml than those who were negative/lowly positive for IgM RF (2.3 [1.9; 3.1], 4.9 [2.9; 16.8], 24.9 [20.4; 45.4], 25.6 [19.9; 57.1], 0.2 [0.01; 1.65], 94.4 [86.3; 138.9], 37.3 [23.6; 47.7], 20.9 [12.3; 33.9], 32.6 [28.1; 37.8], 74.2 [53.5; 147.6], respectively (p < 0.05.Conclusion. There are significant differences in cytokine profile measures in patients with early RA in relation to disease activity and serum autoantibody levels.

  12. Relationship of T regulatory cells content, activity and serum autoantibodies level in patients with systemic lupus erythematosus receiving rituximab

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    A V Torgashina

    2009-04-01

    Full Text Available Objective. To reveal changes of CD+CD25+FoxP3+ T-regulatory cells (T-reg number in pts with systemic lupus erythematosus (SLE receiving rituximab and to assess relationship T reg content with changes of disease activity and serum autoantibodies level during treatment. Material and methods. 12 pts with definite SLE were included. Pts were examined before treatment, after 1, 3 and 6 months. Besides routine laboratory tests anti-double-stranded DNA antibodies, B lymphocytes and T reg cells number was evaluated with flow-cytometry. SLE activity was assessed with SLEDAI 2K scale. Rituximab 500 mg was administered every week iv during 4 weeks. 4 pts received combined treatment with cyclophosphan. Results. Mean age of pts was 30,5±9,8 years (Me 31 years, varied from 18 to 49 years, disease duration varied from 7 to 148 months. T reg number before treatment was not decreased and did not correlated with anti-DNA antibodies level. T reg markers (Foxp3+, CD25+, CD4+CD25+ changes and values of SLE activity on SLEDAI 2K after the end of treatment correlated with presence of clinical response to treatment with rituximab in 3 months. Binary logistic regression model including 4 above mentioned predictors in total allows predicting correctly clinical response to therapy in 83% of cases. Conclusion. Changes of CD25+, CD4+CD25+, CD4+CD25+FoxP3+ T-cells number immediately after the end of treatment with rituximab correlated with clinical effect of the treatment and determined subsequent response to anti-B cell therapy.

  13. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity.

    Science.gov (United States)

    Hammer, C; Stepniak, B; Schneider, A; Papiol, S; Tantra, M; Begemann, M; Sirén, A-L; Pardo, L A; Sperling, S; Mohd Jofrry, S; Gurvich, A; Jensen, N; Ostmeier, K; Lühder, F; Probst, C; Martens, H; Gillis, M; Saher, G; Assogna, F; Spalletta, G; Stöcker, W; Schulz, T F; Nave, K-A; Ehrenreich, H

    2014-10-01

    In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function. PMID:23999527

  14. PREVALENCE OF AUTOANTIBODIES TO THYROID PEROXIDASE AND AUTOIMMUNE THYROID DISEASE IN GIRLS WITH TURNER’S SYNDROME

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    H. Moayeri Z. Oloomi

    2006-07-01

    Full Text Available Patients with Turner’s syndrome (TS are at an increased risk of developing autoimmune thyroid disease (ATD. The aim of this study was to determine the frequency of anti-thyroid peroxidase (anti-Tpo antibodies and ATD in children and adolescent girls with TS. It also assessed the influence of karyotype on the development of thyroid disease. Sixty eight patients with TS were compared with 68 age matched healthy unrelated girls in this study. They were screened for anti-Tpo antibodies, free T4 and TSH levels. Sign and symptoms of hypothyroidism and hyperthyroidism and the presence of goiter were also investigated. Anti-Tpo antibodies were found in 18 (26.4% TS patients and 1 (1.4% patient in the control group (P < 0.001, evenly distributed between the karyotypes 45X, 46X, isoXq and mosaicism. Out of 68 TS patients, 8 (11.7% had visible goiter. Subclinical hypothyroidism and hypothyroidism both occurred in 2 patients (5.9%. These patients were characterized by higher levels of anti-Tpo antibodies. Visible goiter was found in 3 (4.4% subjects of the control group, but all of them were euthyroid. We found that younger patients were more likely to be anti-Tpo negative (P < 0.001. Our data demonstrated a high frequency of ATD in a representative sample of Iranian girls with TS which is in accordance with previous observations. Regular follow up assessment of thyroid autoantibodies and thyroid function in patients with TS is recommended for timely diagnosis of thyroid dysfunction and treatment.

  15. Concomitância de autoanticorpos na esclerose sistêmica: como interpretar? Autoantibodies coexistence in systemic sclerosis: how to interpret it?

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    Scheila Fritsch

    2012-12-01

    Full Text Available Os autoanticorpos possivelmente influenciam as manifestações clínicas da esclerose sistêmica (ES. Essa correlação clínico-sorológica, associada à insuficiência de casos de concomitância de autoanticorpos, originou o paradigma histórico de que seriam mutuamente excludentes. Porém, pode-se questionar essa tese. Poderia a multiplicidade de autoanticorpos significar a coexistência de duas patologias distintas? Por outro lado, se assumidos como anticorpos específicos de uma doença única, essa multiplicidade seria um evento aleatório ou representaria um subgrupo distinto de pacientes, com características clínicas, patogênicas e imunogenéticas próprias? A prevalência de autoanticorpos na ES precoce é elevada. Entretanto, a duplicidade do anticorpo anticentrômero (AAC e do anticorpo antitopoisomerase 1 (AAT é um evento raro. Já a coexistência de AAC, AAT e anticorpo anti-RNA polimerase (anti-RNA-P III ainda não foi descrita em um paciente isolado. Neste relato, com positividade para AAC, AAT e anti-RNA-P III, notamos manifestações vasculares precoces e posterior comprometimento cutâneo limitado. Este parece ser o primeiro relato de concomitância de três autoanticorpos específicos em um paciente com ES. Acreditamos que essa coexistência representa um subgrupo sorológico raro de uma única doença, com possível valor clínico e prognóstico - porém, ainda há necessidade de confirmação.Autoantibodies possibly influence clinical manifestations of systemic sclerosis (SSc. This clinical-serological correlation, associated with the paucity of autoantibodies concomitance, gave rise to the historical paradigm of autoantibodies mutual exclusivity. However, one can question this assumption. Does autoantibodies concomitance mean coexistence of two different entities? On the other hand, if considered a unique disease, is this phenomenon a random event or does it represent a distinct subgroup of patients, with peculiar

  16. Autoantibody in pemphigus serum, specific for the 59 kD keratin, selectively binds the surface of keratinocytes: evidence for an extracellular keratin domain

    International Nuclear Information System (INIS)

    We have identified a novel IgG antikeratin autoantibody in the serum of a Brazilian pemphigus foliaceus patient (Cascas-42). This antibody is specific for the 59 kD acidic murine keratin and its 56.5 kD human counterpart (Moll's catalogue number10), and is distinct from the pemphigus antibody system. Antikeratin autoantibodies present in the Cascas-42 serum were purified by affinity chromatography with a 59 kD murine keratin-agarose column (IAP-Cascas-42 antibodies). The specificity of the IAP-Cascas-42 antibodies was tested by indirect immunofluorescence and immunoelectron microscopy against epidermal cryosections, trypsin-dissociated keratinocytes, and epidermal cell cultures. The serum was also tested with extracts from unlabeled and surface 125I-labeled keratinocytes (Iodo-Gen method) by immunoblot analysis of one- and two-dimensional polyacrylamide gel electrophoresis. The IAP-Cascas-42 antibodies bind the intercellular spaces of murine epidermis, and the cell surfaces of viable, dissociated murine keratinocytes, as well as murine epidermal cells in culture by immunofluorescence and immunoelectron microscopy. These autoantibodies did not stain cytoplasmic keratins and did not react with parallel human epidermal substrates. The Cascas-42 serum identified the 59 kD murine acidic keratin and its 56.5 kD human counterpart in epidermal extracts by two-dimensional polyacrylamide gel electrophoresis and immunoblot analysis. In addition, surface radioiodination of viable murine keratinocytes selectively labeled the 59 kD keratin suggesting that a domain of this molecule is exposed on the cell surface. The 125I-labeled 59 kD keratin was also recognized by the Cascas-42 serum by immunoblotting and autoradiography

  17. Low-dose immunization with adenovirus expressing the thyroid-stimulating hormone receptor A-subunit deviates the antibody response toward that of autoantibodies in human Graves' disease.

    Science.gov (United States)

    Chen, Chun-Rong; Pichurin, Pavel; Chazenbalk, Gregorio D; Aliesky, Holly; Nagayama, Yuji; McLachlan, Sandra M; Rapoport, Basil

    2004-01-01

    Immunization with adenovirus expressing the TSH receptor (TSHR) induces hyperthyroidism in 25-50% of mice. Even more effective is immunization with a TSHR A-subunit adenovirus (65-84% hyperthyroidism). Nevertheless, TSHR antibody characteristics in these mice do not mimic accurately those of autoantibodies in typical Graves' patients, with a marked TSH-blocking antibody response. We hypothesized that this suboptimal antibody response was consequent to the standard dose of TSHR-adenovirus providing too great an immune stimulus. To test this hypothesis, we compared BALB/c mice immunized with the usual number (10(11)) and with far fewer viral particles (10(9) and 10(7)). Regardless of viral dose, hyperthyroidism developed in a similar proportion (68-80%) of mice. We then examined the qualitative nature of TSHR antibodies in each group. Sera from all mice had TSH binding-inhibitory (TBI) activity after the second immunization, with TBI values in proportion to the viral dose. After the third injection, all groups had near-maximal TBI values. Remarkably, in confirmation of our hypothesis, immunization with progressively lower viral doses generated TSHR antibodies approaching the characteristics of autoantibodies in human Graves' disease as follows: 1) lower TSHR antibody titers on ELISA and 2) lower TSH-blocking antibody activity without decrease in thyroid-stimulating antibody activity. In summary, low-dose immunization with adenovirus expressing the free TSHR A-subunit provides an induced animal model with a high prevalence of hyperthyroidism as well as TSHR antibodies more closely resembling autoantibodies in Graves' disease. PMID:14576177

  18. Crohn's disease-specific pancreatic autoantibodies are specifically present in ruminants with paratuberculosis: implications for the pathogenesis of the human disease.

    Science.gov (United States)

    Liaskos, Christos; Spyrou, Vassiliki; Roggenbuck, Dirk; Athanasiou, Labrini V; Orfanidou, Timoklia; Mavropoulos, Athanasios; Reinhold, Dirk; Rigopoulou, Eirini I; Amiridis, Georgios S; Billinis, Charalambos; Bogdanos, Dimitrios P

    2013-09-01

    Mycobacterium avium subspecies paratuberculosis (MAP) induces paratuberculosis (ptb) in ruminants and has clinical and histological features resebling Crohn's disease (CD). Pancreatic autoantibodies (PAB) targeting glycoprotein 2 (GP2) are specifically found in CD, but it is currently unknown whether these autoantibodies can be found in ruminants with ptb. IgG anti-MAP and anti-GP2 antibodies were tested by ELISA in 286 ruminants (212 sheep and 74 cattle). PAB testing was performed by indirect immunofluorescence (IIF) using anti-sheep or anti-cattle specific antisera. PCR analysis confirmed the presence of MAP in anti-MAP positive samples. Anti-GP2 antibodies were more prevalent in anti-MAP antibody positive (26.9%) than in anti-MAP negative ruminants (8.7%, p MAP positive sheep compared to 10/142 (7%, p = 0.001) anti-MAP antibody negative and in anti-MAP positive cattle than in negative counterparts (5/8 versus 8/66, p = 0.003). Absorbance values for anti-GP2 antibodies were higher in cattle than in sheep (mean 21 AU/mL ± 25.4SD versus 12.2 AU/mL ± 23 SD, p MAP antibody concentrations. Anti-GP2 antibodies persisted up to 1/1000 and showed the characteristic IIF pancreatic pattern seen by anti-GP2 antibody positive CD samples. This is the first study to demonstrate the presence of CD-specific GP2-reactive pancreatic autoantibodies in MAP-infected ruminants. Our data suggest that CD and ptb are characterised by an antigen-driven loss of immunological tolerance to GP2, implying commonalities in the immunopathogenesis of the human and ruminant inflammatory bowel disorder. PMID:23638886

  19. Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus.

    Science.gov (United States)

    Kaplan, D; Ferrari, I; Bergami, P L; Mahler, E; Levitus, G; Chiale, P; Hoebeke, J; Van Regenmortel, M H; Levin, M J

    1997-09-16

    Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the beta1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the beta1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-beta1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD. PMID:9294205

  20. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    Energy Technology Data Exchange (ETDEWEB)

    Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

    2013-02-08

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

  1. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    International Nuclear Information System (INIS)

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4+Foxp3+ Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

  2. Use of a High-Density Protein Microarray to Identify Autoantibodies in Subjects with Type 2 Diabetes Mellitus and an HLA Background Associated with Reduced Insulin Secretion.

    Science.gov (United States)

    Chang, Douglas C; Piaggi, Paolo; Hanson, Robert L; Knowler, William C; Bucci, John; Thio, Guene; Hohenadel, Maximilian G; Bogardus, Clifton; Krakoff, Jonathan

    2015-01-01

    New biomarkers for type 2 diabetes mellitus (T2DM) may aid diagnosis, drug development or clinical treatment. Evidence is increasing for the adaptive immune system's role in T2DM and suggests the presence of unidentified autoantibodies. While high-density protein microarrays have emerged as a useful technology to identify possible novel autoantigens in autoimmune diseases, its application in T2DM has lagged. In Pima Indians, the HLA haplotype (HLA-DRB1*02) is protective against T2DM and, when studied when they have normal glucose tolerance, subjects with this HLA haplotype have higher insulin secretion compared to those without the protective haplotype. Possible autoantibody biomarkers were identified using microarrays containing 9480 proteins in plasma from Pima Indians with T2DM without the protective haplotype (n = 7) compared with those with normal glucose regulation (NGR) with the protective haplotype (n = 11). A subsequent validation phase involving 45 cases and 45 controls, matched by age, sex and specimen storage time, evaluated 77 proteins. Eleven autoantigens had higher antibody signals among T2DM subjects with the lower insulin-secretion HLA background compared with NGR subjects with the higher insulin-secretion HLA background (preceiver operating characteristics curve of 0.73, 0.80, and 0.83 (95% CI 0.74-0.91, p = 3.4x10-8), respectively. This study identified 11 novel autoantigens which were associated with T2DM and an HLA background associated with reduced insulin secretion. While further studies are needed to distinguish whether these antibodies are associated with insulin secretion via the HLA background, T2DM more broadly, or a combination of the two, this study may aid the search for autoantibody biomarkers by narrowing the list of protein targets. PMID:26606528

  3. A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies

    DEFF Research Database (Denmark)

    Guldager, Daniel Kring Rasmussen; von Stemann, Jakob Hjorth; Larsen, Rune;

    2015-01-01

    PURPOSE: To establish and validate a rapid, cost-effective and accurate screening assay for the simultaneous testing of human naturally occurring anti-cytokine autoantibodies (c-aAb) targeting interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), granulocyte-macrophage colony...... METHODS: The microsphere-based Luminex platform was used. Recombinant forms of human IL-1α, IL-6, IL-10, GM-CSF, and IFNα were gently coupled to MAG-PLEX beads. Plasma IgG binding was measured with phycoerythrin (PE)-labeled secondary antibodies. Previously confirmed c-aAb positive and negative donor...

  4. Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses.

    Science.gov (United States)

    White, Clayton A; Pone, Egest J; Lam, Tonika; Tat, Connie; Hayama, Ken L; Li, Guideng; Zan, Hong; Casali, Paolo

    2014-12-15

    Class-switch DNA recombination (CSR) and somatic hypermutation (SHM), which require activation-induced cytidine deaminase (AID), and plasma cell differentiation, which requires B lymphocyte-induced maturation protein-1 (Blimp-1), are critical for the generation of class-switched and hypermutated (mature) Ab and autoantibody responses. We show that histone deacetylase inhibitors valproic acid and butyrate dampened AICDA/Aicda (AID) and PRDM1/Prdm1 (Blimp-1) mRNAs by upregulating miR-155, miR-181b, and miR-361 to silence AICDA/Aicda, and miR-23b, miR-30a, and miR-125b to silence PRDM1/Prdm1, in human and mouse B cells. This led to downregulation of AID, Blimp-1, and X-box binding protein 1, thereby inhibiting CSR, SHM, and plasma cell differentiation without altering B cell viability or proliferation. The selectivity of histone deacetylase inhibitor-mediated silencing of AICDA/Aicda and PRDM1/Prdm1 was emphasized by unchanged expression of HoxC4 and Irf4 (important inducers/modulators of AICDA/Aicda), Rev1 and Ung (central elements for CSR/SHM), and Bcl6, Bach2, or Pax5 (repressors of PRDM1/Prdm1 expression), as well as unchanged expression of miR-19a/b, miR-20a, and miR-25, which are not known to regulate AICDA/Aicda or PRDM1/Prdm1. Through these B cell-intrinsic epigenetic mechanisms, valproic acid blunted class-switched and hypermutated T-dependent and T-independent Ab responses in C57BL/6 mice. In addition, it decreased class-switched and hypermutated autoantibodies, ameliorated disease, and extended survival in lupus MRL/Fas(lpr/lpr) mice. Our findings outline epigenetic mechanisms that modulate expression of an enzyme (AID) and transcription factors (Blimp-1 and X-box binding protein 1) that are critical to the B cell differentiation processes that underpin Ab and autoantibody responses. They also provide therapeutic proof-of-principle in autoantibody-mediated autoimmunity. PMID:25392531

  5. The Level of Autoantibodies Targeting Eukaryote Translation Elongation Factor 1 α1 and Ubiquitin-Conjugating Enzyme 2L3 in Nondiabetic Young Adults

    Science.gov (United States)

    Kim, Eunhee G.; Kwak, Soo Heon; Hwang, Daehee; Yi, Eugene C.; Park, Kyong Soo

    2016-01-01

    Background The prevalence of novel type 1 diabetes mellitus (T1DM) antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb) and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb) has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects. Methods EEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (n=150) and T1DM subjects (n=101) in various ranges of age (18 to 69 years) were measured using an enzyme-linked immunosorbent assay. The cutoff point for the presence of each autoantibody was determined based on control subjects using the formula: [mean absorbance+3×standard deviation]. Results In nondiabetic subjects, there were no significant correlations between age and EEF1A1-AAb and UBE2L3-AAb levels. However, there was wide variation in EEF1A1-AAb and UBE2L3-AAb levels among control subjects <40 years old; the prevalence of both EEF1A1-AAb and UBE2L3-AAb in these subjects was 4.4%. When using cutoff points determined from the control subjects <40 years old, the prevalence of both autoantibodies in T1DM subjects was decreased (EEFA1-AAb, 15.8% to 8.9%; UBE2L3-AAb, 10.9% to 7.9%) when compared to the prevalence using the cutoff derived from the totals for control subjects. Conclusion There was no association between age and EEF1A1-AAb or UBE2L3-AAb levels in nondiabetic subjects. However, the wide variation in EEF1A1-AAb and UBE2L3-AAb levels apparent among the control subjects <40 years old should be taken into consideration when determining the cutoff reference range for the diagnosis of T1DM. PMID:26616590

  6. Use of a High-Density Protein Microarray to Identify Autoantibodies in Subjects with Type 2 Diabetes Mellitus and an HLA Background Associated with Reduced Insulin Secretion

    OpenAIRE

    Chang, Douglas C.; Piaggi, Paolo; Hanson, Robert L.; Knowler, William C.; Bucci, John; Thio, Guene; Hohenadel, Maximilian G.; Bogardus, Clifton; Krakoff, Jonathan

    2015-01-01

    New biomarkers for type 2 diabetes mellitus (T2DM) may aid diagnosis, drug development or clinical treatment. Evidence is increasing for the adaptive immune system’s role in T2DM and suggests the presence of unidentified autoantibodies. While high-density protein microarrays have emerged as a useful technology to identify possible novel autoantigens in autoimmune diseases, its application in T2DM has lagged. In Pima Indians, the HLA haplotype (HLA-DRB1*02) is protective against T2DM and, when...

  7. Human rheumatoid factor crossidiotypes. II. Primary structure-dependent crossreactive idiotype, PSL2-CRI, present on Wa monoclonal rheumatoid factors is present on Bla and other IgM kappa monoclonal autoantibodies

    OpenAIRE

    1987-01-01

    The amino acid sequence of the L-CDR2 (complementarity-determining region) of Bla mRF (monoclonal rheumatoid factor) is identical to that of the Wa mRFs. The PSL2-CRI (crossreactive idiotype), as determined by anti-PSL2, which has been shown to be present on all Wa mRFs, is also present on the Bla mRF and other monoclonal autoantibodies. PSL2-CRI is, therefore, not unique to Wa mRFs and may be present on most IgM kappa monoclonal autoantibodies. Whether PSL2-CRI is a crossidiotype (XId) that ...

  8. Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies.

    Science.gov (United States)

    Akamizu, T; Ikuyama, S; Saji, M; Kosugi, S; Kozak, C; McBride, O W; Kohn, L D

    1990-01-01

    A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, Mr 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind 125I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; down-regulation was dependent on TSH concentration and duplicated by forskolin, cholera toxin, or 8-bromo-cAMP but not by a phorbol ester. Down-regulation was also duplicated by thyroid-stimulating autoantibodies, which increased cAMP levels, but not by thyrotropin binding-inhibiting auto-antibodies, which actually increased TSH receptor mRNA levels. Images PMID:1696008

  9. Glutamic acid decarboxylase autoantibody-positivity post-partum is associated with impaired β-cell function in women with gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Lundberg, T. P.; Højlund, K.; Snogdal, L. S.;

    2015-01-01

    AIMS: To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including β-cell function and insulin sensitivity. METHODS: During 1997-2010, 407...... women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin...... similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post...

  10. Monoclonal antibodies to the thyrotropin receptor raised by an autoantiidiotypic protocol and their relationship to monoclonal autoantibodies from Graves' patients

    International Nuclear Information System (INIS)

    Monoclonal antibodies that bind to the TSH receptor were obtained by an autoantiidiotypic approach in which immunization of BALB/c mice was performed with mixtures of bovine (b) and human (h) TSH. Two of 28 positive wells were selected for cloning and characterization: D2 and 4G11. Their antiidiotypic character was evidenced by TSH-inhibitable binding to affinity-purified polyclonal anti-TSH. The specificity of D2 and 4G11 for the hormone-binding region of the TSH receptor was demonstrated by several findings: 1) they inhibited the binding of [125I]iodo-bTSH to receptor in a dose-dependent manner; 2) their binding to partially purified thyroid plasma membranes could be completely inhibited by bTSH and hTSH; and 3) they inhibited the TSH-dependent growth and adenylate cyclase stimulation in FRTL-5 cells in a dose-dependent manner. By Western blot analysis of bovine thyroid membranes, D2 bound to a polypeptide of 188,000-195,000 mol wt under nonreducing conditions and 54,000-59,000 mol wt after treatment of membranes with beta-mercaptoethanol; the 4G11 epitope was undetectable. Scatchard analysis of the binding of 125I-labeled antibodies to receptor showed that 4G11 bound to a single site with a Kd of 5.7 X 10(-9) M, whereas D2 showed complex binding characterized by high affinity (Kd = 1.74 X 10(-11) M) and low affinity (Kd = 1.3 X 10(-8) M) sites. Binding studies in which D2 and 4G11 competed with each other for the TSH receptor showed mutual but unequal inhibition. The data suggest that portions of the D2 and 4G11 epitopes overlap, but that there is a high affinity binding site(s) for D2 for which 4G11 competes less effectively. The binding of D2 and 4G11 to TSH receptor was inhibited by monoclonal antibodies secreted by Graves' heterohybridomas, showing that D2 and 4G11 share characteristics with autoantibodies of Graves' disease

  11. Mesothelial Cell Autoantibodies Induce Collagen Deposition in vitro & Using a Case Study to Introduce Undergraduates to Bioinformatics

    Science.gov (United States)

    Serve, Kinta M.

    Part I. Pleural fibrosis, a non-malignant, asbestos-related respiratory disease characterized by excessive collagen deposition, is progressive, debilitating, and potentially fatal. Disease severity may be influenced by the type of asbestos fiber inhaled, with Libby amphibole (LA) a seemingly more potent mediator of pleural fibrosis than chrysotile (CH) asbestos. This difference in severity may be due to the reported immunological component associated with LA but not CH related diseases. Here, we report the potential mechanisms by which asbestos-associated mesothelial cell autoantibodies (MCAAs) contribute to pleural fibrosis development. MCAAs are shown to bind cultured human pleural mesothelial cells and induce the deposition of type I collagen proteins in the absence of phenotypic changes typically associated with fibrosis development. However, additional extracellular proteins seem to differentially contribute to LA and CH MCAA-associated collagen deposition. Our data also suggest that IgG subclass distributions differ between LA and CH MCAAs, potentially altering the antibody effector functions. Differences in MCAA mechanisms of action and effector functions may help explain the disparate clinical disease phenotypes noted between LA and CH-exposed populations and may provide insights for development of novel therapeutic strategies. Part II. As scientific research becomes increasingly reliant on computational tools, it is more important than ever before to train students to use these tools. While educators agree that biology students should gain experience with bioinformatics, there exists no consensus as to how to integrate these concepts into the already demanding undergraduate curriculum. The Portal-21 project offers a solution by utilizing on-line learning case studies to allow flexibility for classroom integration. Presented here are the results from two field tests of a case study developed to introduce the common bioinformatics tools pBLAST and PubMed to

  12. Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

    Directory of Open Access Journals (Sweden)

    Yavelsky Victoria

    2008-08-01

    Full Text Available Abstract Background We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. Methods The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. Results By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line. To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. Conclusion The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein

  13. Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

    International Nuclear Information System (INIS)

    We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that

  14. Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Yongkang Wu

    2014-01-01

    Full Text Available Background & objectives: The presence of CD4+CD8+ (double positive T cells (DPT in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE. Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA, anti-double strain deoxyribonucleic acid (anti-dsDNA, anti-U1 ribonucleoprotein (anti-U1 RNP, anti-sjogren syndrome A (anti-SSA, anti-ribosomal P protein (anti-rib-P, anti-Smith (anti-Sm, anti-Sjogren syndrome B (anti-SSB, complement 3 (C3 and complement 4 (C4. Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001. SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032. The DPT medians of positive subgroups with anti-dsDNA (P<0.001, anti-U1RNP (P=0.018, anti-SSA (P=0.021 or anti-rib-P (P=0.039 were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006. Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

  15. Autoantibodies against human insulin.

    OpenAIRE

    Wilkin, T J; Nicholson, S.

    1984-01-01

    Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only hum...

  16. The major autoantibody epitope on factor H in atypical hemolytic uremic syndrome is structurally different from its homologous site in factor H-related protein 1, supporting a novel model for induction of autoimmunity in this disease.

    Science.gov (United States)

    Bhattacharjee, Arnab; Reuter, Stefanie; Trojnár, Eszter; Kolodziejczyk, Robert; Seeberger, Harald; Hyvärinen, Satu; Uzonyi, Barbara; Szilágyi, Ágnes; Prohászka, Zoltán; Goldman, Adrian; Józsi, Mihály; Jokiranta, T Sakari

    2015-04-10

    Atypical hemolytic uremic syndrome (aHUS) is characterized by complement attack against host cells due to mutations in complement proteins or autoantibodies against complement factor H (CFH). It is unknown why nearly all patients with autoimmune aHUS lack CFHR1 (CFH-related protein-1). These patients have autoantibodies against CFH domains 19 and 20 (CFH19-20), which are nearly identical to CFHR1 domains 4 and 5 (CFHR14-5). Here, binding site mapping of autoantibodies from 17 patients using mutant CFH19-20 constructs revealed an autoantibody epitope cluster within a loop on domain 20, next to the two buried residues that are different in CFH19-20 and CFHR14-5. The crystal structure of CFHR14-5 revealed a difference in conformation of the autoantigenic loop in the C-terminal domains of CFH and CFHR1, explaining the variation in binding of autoantibodies from some aHUS patients to CFH19-20 and CFHR14-5. The autoantigenic loop on CFH seems to be generally flexible, as its conformation in previously published structures of CFH19-20 bound to the microbial protein OspE and a sialic acid glycan is somewhat altered. Cumulatively, our data suggest that association of CFHR1 deficiency with autoimmune aHUS could be due to the structural difference between CFHR1 and the autoantigenic CFH epitope, suggesting a novel explanation for CFHR1 deficiency in the pathogenesis of autoimmune aHUS. PMID:25659429

  17. Susceptibility for Lupus Nephritis by Low Copy Number of the FCGR3B Gene Is Linked to Increased Levels of Pathogenic Autoantibodies

    Directory of Open Access Journals (Sweden)

    Johannes C. Nossent

    2013-01-01

    Full Text Available Low copy number (CN of the FCGR3B gene reduces FCGR3B membrane expression on neutrophils and results in clearance of a smaller amount of immune complex. We investigated FCGR3B CN in relation to the clinical phenotype in a Caucasian SLE cohort (. FCGR3B CN was determined by three different qPCR parameter estimations (Ct−, Cy0, and cpD1 and confirmed by the FCGR2C/FCGR2A paralog ratio test. Clinical and serological data were then analyzed for their association with FCGR3B CN. Low FCGR3B CN (2. In multivariate analyses, LN was independently associated with anti-C1q-Ab levels ( and low FCGR3B CN (. We conclude that the susceptibility for LN in patients with low FCGR3B CN is linked to increased levels of pathogenic autoantibodies.

  18. 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 (Pantibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (Pantibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (PRNP or anti-SSA antibody should be performed. PMID:24864270

  19. Methyl-binding domain protein-based DNA isolation from human blood serum combines DNA analyses and serum-autoantibody testing

    Directory of Open Access Journals (Sweden)

    Jungbauer Christof

    2011-09-01

    Full Text Available Abstract Background Circulating cell free DNA in serum as well as serum-autoantibodies and the serum proteome have great potential to contribute to early cancer diagnostics via non invasive blood tests. However, most DNA preparation protocols destroy the protein fraction and therefore do not allow subsequent protein analyses. In this study a novel approach based on methyl binding domain protein (MBD is described to overcome the technical difficulties of combining DNA and protein analysis out of one single serum sample. Methods Serum or plasma samples from 98 control individuals and 54 breast cancer patients were evaluated upon silica membrane- or MBD affinity-based DNA isolation via qPCR targeting potential DNA methylation markers as well as by protein-microarrays for tumor-autoantibody testing. Results In control individuals, an average DNA level of 22.8 ± 25.7 ng/ml was detected applying the silica membrane based protocol and 8.5 ± 7.5 ng/ml using the MBD-approach, both values strongly dependent on the serum sample preparation methods used. In contrast to malignant and benign tumor serum samples, cell free DNA concentrations were significantly elevated in sera of metastasizing breast cancer patients. Technical evaluation revealed that serum upon MBD-based DNA isolation is suitable for protein-array analyses when data are consistent to untreated serum samples. Conclusion MBD affinity purification allows DNA isolations under native conditions retaining the protein function, thus for example enabling combined analyses of DNA methylation and autoantigene-profiles from the same serum sample and thereby improving minimal invasive diagnostics.

  20. Severity of dry eye syndrome is related to anti-dsDNA autoantibody in systemic lupus erythematosus patients without secondary Sjogren syndrome: A cross-sectional analysis.

    Science.gov (United States)

    Chen, Alexander; Chen, Hung-Ta; Hwang, Yih-Hsiou; Chen, Yi-Tsun; Hsiao, Ching-Hsi; Chen, Hung-Chi

    2016-07-01

    There are as many as one-third of the systemic lupus erythematosus (SLE) patients who suffer from dry eye syndrome. To this date, dry eye syndrome in SLE patients is believed to be caused by secondary Sjogren syndrome (sSS). However, there is increasing evidence for possible independency of dry eye syndrome and sSS in patients suffering from autoimmune diseases. The purpose of this retrospective observational case series was to identify SLE patients without sSS who had dry eye syndrome, examine the correlation of different autoantibodies and dry eye severity, and determine the cause of dry eye in these patients.We included 49 consecutive SLE patients with dry eye who visited our dry eye clinic. In order to rule out sSS, these patients were all negative for anti-Sjogren's-syndrome-related antigen A and B (anti-SSA/SSB) and had no oral symptoms. Each patient's lupus activity was determined by serological tests including antidouble-stranded DNA antibody (anti-dsDNA), complement levels (C3, C4), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA). Severity of dry eye syndrome was determined by corneal sensation (KSen), superficial punctuate keratopathy (SPK), Schirmer-I test (Schirmer), and tear film break-up time (TBUT). The autoantibodies and the dry eye parameters in each group were tested using the χ test or the Mann-Whitney U test for normally distributed or skewed data, respectively.The anti-dsDNA showed significant correlations with KSen (P C3 showed significant correlations with KSen (P C3 but not with C4, ESR, and ANA. PMID:27428227

  1. Severity of dry eye syndrome is related to anti-dsDNA autoantibody in systemic lupus erythematosus patients without secondary Sjogren syndrome

    Science.gov (United States)

    Chen, Alexander; Chen, Hung-Ta; Hwang, Yih-Hsiou; Chen, Yi-Tsun; Hsiao, Ching-Hsi; Chen, Hung-Chi

    2016-01-01

    Abstract There are as many as one-third of the systemic lupus erythematosus (SLE) patients who suffer from dry eye syndrome. To this date, dry eye syndrome in SLE patients is believed to be caused by secondary Sjogren syndrome (sSS). However, there is increasing evidence for possible independency of dry eye syndrome and sSS in patients suffering from autoimmune diseases. The purpose of this retrospective observational case series was to identify SLE patients without sSS who had dry eye syndrome, examine the correlation of different autoantibodies and dry eye severity, and determine the cause of dry eye in these patients. We included 49 consecutive SLE patients with dry eye who visited our dry eye clinic. In order to rule out sSS, these patients were all negative for anti-Sjogren's-syndrome-related antigen A and B (anti-SSA/SSB) and had no oral symptoms. Each patient's lupus activity was determined by serological tests including antidouble-stranded DNA antibody (anti-dsDNA), complement levels (C3, C4), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA). Severity of dry eye syndrome was determined by corneal sensation (KSen), superficial punctuate keratopathy (SPK), Schirmer-I test (Schirmer), and tear film break-up time (TBUT). The autoantibodies and the dry eye parameters in each group were tested using the χ2 test or the Mann–Whitney U test for normally distributed or skewed data, respectively. The anti-dsDNA showed significant correlations with KSen (P C3 showed significant correlations with KSen (P C3 but not with C4, ESR, and ANA. PMID:27428227

  2. Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-Ak NOD mice

    Science.gov (United States)

    Pelletier, Adam-Nicolas; Aliesky, Holly A.; Banuelos, Bianca; Chabot-Roy, Geneviève; Rapoport, Basil; Lesage, Sylvie; McLachlan, Sandra M

    2015-01-01

    NOD.H2k and NOD.H2h4 mice carry the MHC class II molecule I-Ak associated with susceptibility to experimentally-induced thyroiditis. Dietary iodine enhanced spontaneous thyroid autoimmunity, well known in NOD.H2h4 mice, has not been investigated in NOD.H2k mice. We compared NOD.H2h4 and NOD.H2k strains for thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) without or with dietary sodium iodide (NaI) for up to 32 weeks. TgAb levels were significantly higher in NOD.H2h4 than NOD.H2k mice on NaI and TPOAb developed in NOD.H2h4 but not NOD.H2k mice. DNA exome analysis revealed, in addition to the differences in the chromosome (Chr) 17 MHC regions, that NOD.H2k and particularly NOD.H2h4 mice have substantial non-MHC parental DNA. KEGG pathway-analysis highlighted thyroid autoimmunity and immune-response genes on Chr 17 but not on Chr 7 and 15 parental B10.A4R DNA. Studies of parental strains provided no evidence for non-MHC gene contributions. The exon 10 thyroglobulin haplotype, associated with experimentally-induced thyroiditis, is absent in NOD.H2h4 and NOD.H2k mice and is not a marker for spontaneous murine thyroid autoimmunity. In conclusion, the absence of I-E is a likely explanation for the difference between NOD.H2h4 and NOD.H2k mice in TgAb levels and, as in humans, autoantibody spreading to TPO. PMID:25811933

  3. Association of adiponectin, interleukin (IL)-1ra, inducible protein 10, IL-6 and number of islet autoantibodies with progression patterns of type 1 diabetes the first year after diagnosis

    DEFF Research Database (Denmark)

    Pfleger, Claudia Christina; Hansen, Lene; Buschard, K;

    2010-01-01

    The progression of type 1 diabetes after diagnosis is poorly understood. Our aim was to assess the relation of disease progression of juvenile-onset type 1 diabetes, determined by preserved beta cell function the first year after diagnosis, with systemic cytokine concentrations and number of...... autoantibodies. Juvenile patients (n = 227) had a meal-stimulated C-peptide test 1 and 6 months after diagnosis. On the basis of the C-peptide course for the duration of 1-6 months, four progression groups were defined: patients with persistently low beta cell function ('stable-low'), rapid progressers, slow...... patients (P = 0·03 and P = 0·006). IL-1ra, IP-10 and IL-6 did not differ between the groups at any time-point. The number of autoantibodies differed significantly between the groups at 1 month (P = 0·04), where rapid progressers had the largest number. There was no difference between the groups in human...

  4. Accuracy of receptor-based methods for detection of thyrotropin-receptor autoantibodies: a new automated third-generation immunoassay shows higher analytical and clinical sensitivity for the differential diagnosis of hyperthyroidism

    OpenAIRE

    Tozzoli, Renato; Kodermaz, Graziano; Villalta, Danilo; Bagnasco, Marcello; Pesce, Giampaola; Bizzaro, Nicola

    2010-01-01

    Purpose Specific autoantibodies acting as TSH receptor agonists (TRAb) are responsible for Graves’ disease (GD). In the last 30 years three generations of assay methods for the detection of TRAb have become available. The aim of this multicentre study was to evaluate the analytical sensitivity, precision and diagnostic accuracy of TRAb measurement using a new automated assay in comparison with a second-generation standard method. Methods Serum samples from patients with GD (n=82), autoimmune ...

  5. Population of antithyroid autoantibodies as a source of antibodies of various levels of specificity and functionality: the clinical importance of a phenomenon of combination theory at monitoring of patients with autoimmune diseases of a thyroid gland

    Directory of Open Access Journals (Sweden)

    A V Andreeva

    2011-06-01

    Full Text Available The review of literature is dedicated to comparative analysis of pathogenetic and clinicodiagnostic significance of antithyroid autoantibodies (autoAB differing in their specificity (АB to thyroglobulin (anti-TG and АB to thyroid peroxidase (anti-TPO, anti-TGPO, and functionality TG- and TPO-antibodies, namely antibodies-proteases in pathogenesis autoimmune diseases thyroid gland and possibility of their use in modern diagnostics of autoimmune thyroid diseases.

  6. Estudo de imunoglobulinas, complementos e auto-anticorpos em 58 trabalhadores expostos à sílica Immunoglobulins, complements and autoantibodies in 58 workers exposed to silica

    Directory of Open Access Journals (Sweden)

    Hermano Albuquerque de Castro

    2004-06-01

    Full Text Available INTRODUÇÃO: A silicose é a doença pulmonar ocupacional de maior prevalência em nosso meio. O agente patogênico da silicose é a poeira de sílica-livre ou dióxido de silício (SiO2 na forma cristalina. O processo inflamatório envolvendo o sistema imunológico na silicose ainda não está bem esclarecido. OBJETIVO: Estudar o perfil de IgG, IgM, IgA, C3, C4 e alguns auto-anticorpos no soro de trabalhadores expostos à sílica, com ou sem silicose, através de avaliação laboratorial imunológica, abrangendo tanto a imunidade inespecífica quanto a específica. MÉTODO: Foi examinada uma amostra de 58 pacientes ambulatoriais, do sexo masculino, constituída por trabalhadores expostos à sílica. Foram realizadas avaliações imunológica, radiológica e funcional pulmonar. Foram dosadas as imunoglobulinas IgG, IgA e IgM, os componentes C3 e C4 do sistema complemento e determinados auto-anticorpos. RESULTADOS: Vinte trabalhadores apresentaram radiograma normal e 38 apresentaram-no alterado, compatível com silicose. As médias dos valores de IgG no grupo com silicose foi maior que no grupo com radiograma normal (p 0.05. O percentual de positividade dos auto-anticorpos foi maior no grupo silicótico em relação ao grupo com radiograma normal. CONCLUSÃO: O aumento de IgG nos doentes com silicose constitui um achado importante pois pode indicar a continuidade da reação granulomatosa, mesmo com o trabalhador afastado da exposição. Entretanto, ainda são necessários estudos que possibilitem a compreensão do processo imunogênico na silicose.BACKGROUND: The primary work-related lung disease in Brazil is silicosis. Its pathogenic agent is the dust of crystalline free silica (SiO2; silicon dioxide. The inflammatory process of silicosis is not yet well understood. OBJECTIVE: To analyze, through immunologic laboratory evaluation, including nonspecific and specific immunity, the profile of IgG, IgM, IgA, C3, C4 and autoantibodies in the serum

  7. C1-inhibitor (C1-INH) autoantibodies in hereditary angioedema. Strong correlation with the severity of disease in C1-INH concentrate naïve patients.

    Science.gov (United States)

    Varga, Lilian; Széplaki, Gábor; Visy, Beáta; Füst, George; Harmat, George; Miklós, Katalin; Németh, Julianna; Cervenak, László; Karádi, István; Farkas, Henriette

    2007-02-01

    The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p<0.001). Surprisingly, high titer IgM C1-INH-Abs were present with equal frequency in the 41 HAE patients ever treated with C1-INH concentrate and in the 54 C1-INH treatment naïve patients. In the latter group, strong positive correlation between the levels of the IgM C1-INH-Abs and the most severe disease (score 1) (p=0.0021) and the yearly attack rate (p=0.0173) were obtained. In addition, the levels of the IgM C1-INH-Abs exhibited strong negative correlation to the C1-inhibitor concentration and functional activity, total classical complement pathway activity, and a positive correlation to total IgM concentration. Taken together, these data indicate that IgM type C1-INH-Abs are present with highly elevated frequency in HAE patients irrespectively of the previous treatment with C1-INH concentrate. Most probable production of these autoantibodies is the consequence of the activation of complement and other plasma enzyme systems during HAE attacks. Determination of IgM C1

  8. The Prognostic Role of Angiotensin II Type 1 Receptor Autoantibody in Non-Gravid Hypertension and Pre-eclampsia: A Meta-analysis and Our Studies.

    Science.gov (United States)

    Lei, Jinghui; Li, Yafeng; Zhang, Suli; Wu, Ye; Wang, Pengli; Liu, Huirong

    2016-04-01

    Angiotensin II type 1 receptor autoantibody (AT1-AA) is found in patients with non-gravid hypertension or pre-eclampsia, but the relationship is uncertain.The aim of the present study was to assess the association between AT1-AA and high blood pressure using meta-analysis, and to evaluate the prognosis value of AT1-AA for hypertensive diseases.Literature search from PubMed, Embase, and Cochrane databases were conducted using keywords "hypertension" or "pre-eclampsia," "angiotensin II receptor type 1 autoantibody," and its aliases from April 1999 to December 2015.Studies evaluating the association between AT1-AA and non-gravid hypertension or pre-eclampsia were included in this analysis. The quality of the eligible studies was assessed based on the Newcastle-Ottawa Scale with some modifications.Two researchers then independently reviewed all included studies and extracted all relevant data. Association between AT1-AA and hypertension was tested with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Finally, we evaluated whether AT1-AA predicted the prognosis of hypertension by using a summary receiver-operating characteristic (ROC) curve and sensitivity analysis.Ten studies were finally included in this meta-analysis. AT1-AA showed more significant association with pre-eclampsia than that with non-gravid hypertension (pooled OR 32.84, 95% CI 17.19-62.74; and pooled OR 4.18, 95% CI 2.20-7.98, respectively). Heterogeneity among studies was also detected probably due to different hypertensive subtypes and AT1-AA measuring methods. Area under summary ROC curve (AUC) of pre-eclampsia was 0.92 (sensitivity 0.76; specificity 0.86). Area under the ROC curve of overall hypertensive diseases or non-gravid hypertension was lower than that of pre-eclampsia (0.86 and 0.72, respectively) with lower sensitivities (0.46 and 0.26, respectively).The major limitation of this analysis was the publication bias due to lack of unpublished data and the language limitation during

  9. Study on serum autoantibodies of patients with polycystic ovary syndrome%多囊卵巢综合征患者血清自身抗体研究

    Institute of Scientific and Technical Information of China (English)

    钮玉洁

    2012-01-01

    目的:探讨多囊卵巢综合征(PCOS)患者血清自身抗体水平.方法:选择就诊于该院的PCOS患者35例为研究组,非PCOS患者35例为对照组,间接免疫荧光法(IIF)检测抗核抗体(ANA)、线性免疫印迹法(LIA)检测血清抗组蛋白抗体、抗Sm抗体、抗双链DNA抗体、抗核小体抗体水平.结果:PCOS患者血清抗组蛋白抗体、抗双链DNA抗体与对照组存在统计学差异,抗核抗体、抗Sm抗体、抗核小体抗体无统计学差异.结论:PCOS患者存在血清自身抗体阳性,自身免疫可能涉及PCOS发病或疾病进展.%Objective: To explore the levels of serum autoantibodies of patients with polycystic ovary syndrome (PCOS) . Methods:A total of 35 patients with PCOS were selected from the hospital as study group, and 35 patients without PCOS were selected from the hospital as control group; indirect immunofluorescence assay (11F) was used to detect the level of antinuclear antibody (ANA), line im-munoassay (LI A) was used to detect the levels of serum anti - histone antibody ( AHA), anti - Sm antibody, anti - double stranded DNA antibody, and anti - nucleosome antibody. Results: There was statistically significant difference in the levels of serum AHA and anti - double stranded DNA antibody between the two groups; there was no statistically significant difference in the levels of ANA, anti -Sm antibody, and anti - nucleosome antibody between the two groups. Conclusion: PCOS patients had positive serum autoantibodies, autoimmunity may be involved into the occurrence and development of PCOS.

  10. Expression of immune autoantibodies in children with persistent/chronic immune thrombocytopenia%持续性和慢性免疫性血小板减少症患儿免疫抗体表达的意义

    Institute of Scientific and Technical Information of China (English)

    李珊珊; 蒋慧; 夏敏

    2015-01-01

    Objective To investigate the expression and clinical significance of platelet autoantibodies in children with persistent/chronic immune thrombocytopenia (pITP/cITP).Methods Total of 34 children diagnosed with pITP/cITP(14 cases and 20 cases,respectively)in the Department of Hematology and Oncology,Shanghai Children's Hospital from December 2013 to August 2014 were enrolled as the study group,including 20 male and 14 female,the median age of 5 years old.The study also included 20 healthy children (the healthy control group) matched with gender and age,and 24 cases of newly diagnosed ITP (newly diagnosed ITP group) serving as the control groups.Platelet-associated immunoglobulin (PAIg) and platelet-specific autoantibodies on surface of platelets were mea-sured by flow cytometry or flow cytometric bead.Results Significant elevation of PAIgA,PAIgM,PAIgD and specific autoantibodies against glucoprotein(GP) Ⅲa,and GP Ⅱb were demonstrated in children with cITP,as well as specific autoantibodies against GP Ⅰ b,GP Ⅲ a,GP Ⅱ b,and granule membrane protein 140 (GMP140) in children with pITP,compared with the healthy control group(P < 0.05);the levels of GPⅨ,GP Ⅲ a,GMP140 in cITP group and GP Ⅱ b in pITP showed significant declination,compared with the newly diagnosed ITP group(P < 0.05);between piTP group and cITP group,autoantibodies GPⅨ,GP Ⅰ b,GP Ⅱ b,and GMP140 in the latter were much lower(P < 0.05).Significant negative relation between PAIgM and platelet count was found in cITP group (P < 0.05).Receiver operating characte-ristic (ROC) curve analysis showed that the area under ROC curve (AUC) of GP Ⅲ a autoantibodies was larger than that of other platelet-autoantibodies in pITP/ciTP diagnosis.Conclusions Platelet autoantibodies play a significant role in pITP/ciTP,especially platelet-specific autoantibodies,which show a declining tendency in the course and may be the main mechanism.The detection of GPⅢa specific autoantibody is more

  11. Anti-early endosome antigen 1 autoantibodies were detected in a pemphigus-like patient but not in the majority of pemphigus diseases.

    Science.gov (United States)

    Nishikawa, Ryuhei; Takahashi, Hitoshi; Matsuda, Mitsuhiro; Imaoka, Kaoru; Ogawa, Masahiro; Teye, Kwesi; Tsuchisaka, Atsunari; Koga, Hiroshi; Komorowski, Lars; Probst, Christian; Hachiya, Takahisa; Fritzler, Marvin J; Ishii, Norito; Ohata, Chika; Furumura, Minao; Krol, Rafal P; Muro, Yoshinao; Morita, Eishin; Hashimoto, Takashi

    2016-05-01

    Although the major autoantigens in classic pemphigus are desmogleins, sera from various types of pemphigus react with a number of other molecules, including desmocollins and plakin proteins. However, other novel pemphigus-related autoantigens remain to be identified. In this study, immunoblotting for serum from an atypical autoimmune bullous disease patient identified an unknown 175 kDa protein. Subsequent studies using two-dimensional gel electrophoresis, immunoblotting and mass-spectrometry identified the 175 kDa protein as early endosome antigen 1 (EEA1). This finding was confirmed by subsequent immunological studies, including indirect immunofluorescence of skin and cultured keratinocytes, two-dimensional gel electrophoresis and immunoblotting with anti-EEA1 polyclonal antibody, and preabsorption with EEA1 recombinant protein. Finally, we developed a novel BIOCHIP assay using full-length EEA1 recombinant protein to detect anti-EEA1 antibodies. However, none of 35 sera from various types of pemphigus showed anti-EEA1 antibodies in the BIOCHIP assay, with the exception of the serum from the index case. In addition, various findings in the index case did not suggest pathogenic role of anti-EEA1 autoantibodies. Therefore, although we successfully identified the 175 kDa protein reacted by a serum of an atypical pemphigus-like patient as EEA1, novel BIOCHIP study for other pemphigus sera indicated that EEA1 is not a common and pathogenic autoantigen in pemphigus. PMID:26909655

  12. Methimazole, but not betamethasone, prevents 131I treatment-induced rises in thyrotropin receptor autoantibodies in hyperthyroid Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Gamstedt, A.; Wadman, B.; Karlsson, A.

    1986-04-01

    The effects of methimazole or betamethasone therapy on the TSH receptor antibody response to radioiodine therapy were compared in a prospective randomized study of 60 patients with hyperthyroidism due to Graves' disease. The patients were followed for 1 yr after treatment with 131I. Twenty-three patients received 131I alone, 17 were treated with methimazole for 2 months before and 3 months after 131I therapy, and 20 patients were treated with betamethasone for 3 weeks before and 4 weeks after 131I therapy. 131I induced a transient rise in the mean serum level of TSH receptor autoantibodies, measured as TSH binding inhibitory immunoglobulin (TBII), but in patients receiving methimazole treatment, no such rise occurred. In the betamethasone-treated patients, TBII increased similarly to that in patients treated with 131I alone. In addition, in patients given betamethasone, there was an early decrease in total serum immunoglobulin G, which persisted throughout the follow-up period. In the other 2 groups, no changes in total immunoglobulin G were found. The results demonstrate that in hyperthyroid Graves' disease, TBII production is influenced by therapy. Methimazole abolished the 131I-induced increase in TBII, whereas betamethasone did not have such an inhibitory effect.

  13. Light chain (κ/λ) ratio of GM-CSF autoantibodies is associated with disease severity in autoimmune pulmonary alveolar proteinosis.

    Science.gov (United States)

    Nei, Takahito; Urano, Shinya; Itoh, Yuko; Kitamura, Nobutaka; Hashimoto, Atsushi; Tanaka, Takahiro; Motoi, Natsuki; Kaneko, Chinatsu; Tazawa, Ryushi; Nakagaki, Kazuhide; Arai, Toru; Inoue, Yoshikazu; Nakata, Koh

    2013-12-01

    Previous studies demonstrated that antigranulocyte colony-stimulating factor autoantibody (GMAb) was consistently present in patients with autoimmune pulmonary alveolar proteinosis (aPAP), and, thus, represented candidature as a reliable diagnostic marker. However, our large cohort study suggested that the concentration of this antibody was not correlated with disease severity in patients. We found that the κ/λ ratio of GMAb was significantly correlated with the degree of hypoxemia. The proportion of λ-type GMAb per total λ-type IgG was significantly higher in severely affected patients than those in mildly affected patients, but the proportion of κ-type was unchanged. The κ/λ ratio was significantly correlated with both KL-6 and SP-D, which have been previously reported as disease severity markers. Thus, the light chain isotype usage of GMAb may not only be associated with the severity of aPAP, but may also represent a useful disease severity marker. PMID:24211842

  14. Neutralization of pathogenic beta1-receptor autoantibodies by aptamers in vivo: the first successful proof of principle in spontaneously hypertensive rats.

    Science.gov (United States)

    Haberland, Annekathrin; Wallukat, Gerd; Berg, Sabine; Schulz, Angela-Martina; Freyse, Ernst-Joachim; Vetter, Roland; Salzsieder, Eckhard; Müller, Johannes; Kreutz, Reinhold; Schimke, Ingolf

    2014-08-01

    Autoantibodies (AABs) against the second extracellular loop of the beta1-receptor (beta1(II)-AABs) are found as a pathogenic driver in patients with idiopathic dilated cardiomyopathy, Chagas cardiomyopathy, peripartum cardiomyopathy, and myocarditis, and have been increasingly seen as a treatment target. We recently identified an aptamer (single short DNA strand) that specifically binds and neutralizes beta1(II)-AABs. Via application of this aptamer, a new treatment strategy for diseases associated with the cardio-pathogenic beta1(II)-AABs could be developed. Spontaneously hypertensive rats (SHR) positive for beta1(II)-AABs were treated five times at weekly intervals (bolus application of 2 mg/kg body weight followed by an infusion of the same amount over 20 min). SHR responded to aptamer treatment with a strong reduction in the cardio-pathogenic beta1(II)-AABs. The AABs did not substantially return within the study period. No signs for aptamer toxicity were observed by visual examination of the heart, liver, and kidney, or by measurement of plasma CK, ALT, and creatinine. The aptamer's potential for beta1(II)-AAB neutralization and consequently for cardiomyopathy treatment has been shown for the first time in vivo. PMID:24744110

  15. sup(99m)TcO4-uptake and TSH receptor autoantibodies - a comparative study in Graves' disease and other diseases of the thyroid

    International Nuclear Information System (INIS)

    In 255 patients (normals: group I, n=30; nontoxic goitres: group II, n=134; toxic goitres without ophthalmopathy: group III, n=63; Graves' disease: group IV, n=28) a TSH-receptor-autoantibody-assay (TRAK assay) for detection of thyrotropin-binding inhibiting antibodies (TBIAb) was tested and sup(99m)TcO4-uptake (TcTU) was measured. Normal TcTU (range: 1.5-5.5%) and normal TRAK values (normal limit: F<11%) were only found in group I. An increased TcTU was found in group II in 22.4% (increased TRAK values only in 2.2%). In group III an increased TcTU was measured in 34.9% of the patients (all with normal TRAK titers). The stimulation of the TSH-receptor in immunogenic hyperthyroidism by TBIAb could be demonstrated by in creased TRAK values in 71.4% of the patients with Graves' disease. In correlation, TcTU was also increased in 82.1% of the patients in group IV. As the measurement of TcTU can be helpful in differential diagnosis, the functional imaging with gamma camera and computer is today a conditio sine qua non, especially in suspected hyperthyroidism. (orig.)

  16. Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse.

    Science.gov (United States)

    Thai, To-Ha; Patterson, Heide Christine; Pham, Duc-Hung; Kis-Toth, Katalin; Kaminski, Denise A; Tsokos, George C

    2013-12-10

    MicroRNA-155 (miR-155) regulates antibody responses and subsequent B-cell effector functions to exogenous antigens. However, the role of miR-155 in systemic autoimmunity is not known. Using the death receptor deficient (Fas(lpr)) lupus-prone mouse, we show here that ablation of miR-155 reduced autoantibody responses accompanied by a decrease in serum IgG but not IgM anti-dsDNA antibodies and a reduction of kidney inflammation. MiR-155 deletion in Fas(lpr) B cells restored the reduced SH2 domain-containing inositol 5'-phosphatase 1 to normal levels. In addition, coaggregation of the Fc γ receptor IIB with the B-cell receptor in miR-155(-/-)-Fas(lpr) B cells resulted in decreased ERK activation, proliferation, and production of switched antibodies compared with miR-155 sufficient Fas(lpr) B cells. Thus, by controlling the levels of SH2 domain-containing inositol 5'-phosphatase 1, miR-155 in part maintains an activation threshold that allows B cells to respond to antigens. PMID:24282294

  17. 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.

  18. Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Paola Cordiali-Fei

    2013-01-01

    Full Text Available In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc and undifferentiated connective tissue disease (UCTD, we have explored the setting of peripheral T regulatory (T reg cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc or diffuse (dcSSc disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.

  19. A three-layer immunoradiometric assay for antibodies in different immunoglobulin classes and its application to the detection of chicken thyroglobulin autoantibodies and of antibodies to sheep erythrocytes

    International Nuclear Information System (INIS)

    A versatile solid-phase assay for detection of antibodies in different immunoglobulin classes is described. The assay has been applied to: (1) the detection of IgG and IgM antithyroglobulin autoantibodies in chickens with spontaneous autoimmune thyroiditis, and (2) the detection of anti-sheep cell antibodies in normal chickens. Thyroglobulin-coated plastic tubes or formaldehyde-fixed sheep erythrocytes were used as the solid phase. Antisera were added in succession to the solid-phase antigen so as to form 3 antibody layers: (1) chicken antibody against the solid-phase antigen; (2) heavy-chain-specific rabbit anti-chicken immunoglobulin; and (3) 125I-labelled goat anti-rabbit immunoglobulin. The assay is suitable for routine determinations on large numbers of samples; its sensitivity enables small volumes of serum to be tested and allows considerable economy in the use of valuable class-specific antisera. The radiolabelled reagent can be readily applied to other assays employing rabbit antisera. (Auth.)

  20. Thyroid Autoantibodies and Recurrent Abortion Related Research%甲状腺自身抗体与复发性流产的相关研究

    Institute of Scientific and Technical Information of China (English)

    耿顺玲; 付锦华

    2013-01-01

    目的:观察甲状腺自身抗体( ATA )及促甲状腺激素( TSH )对复发性流产( RSA )的影响。方法选取我院118例早期妊娠患者进行常规检查甲状腺功能,其中73例既往有过2次以上不明原因的流产史患者作为研究组,并以45例既往无不良妊娠史的育龄妇女作为对照组。结果 RSA患者中甲状腺抗体ATA,TPOAb, TGAb阳性率与对照组相比较,P<0.05,均有统计学差异;甲状腺抗体阳性且伴有促甲状腺激素( TSH)≥3.93mIU的流产率为83.33%与单纯性甲状腺抗体阳性的患者流产率23.53%比较,P<0.05,两组比较有统计学差异。结论甲状腺自身抗体阳性与复发性流产关系密切,TSH升高是流产的危险因子,建议两者为孕早期常规筛查。%Objective To study thyroid autoantibodies ( ATA) and thyroid stimulating hormone TSH for re-current miscarriage ( RSA) effects.Methods One hundred and eighteen cases of early pregnancy in our hospital for rou-tine examination of thyroid function in patients were chosen ,including 73 cases with a history of more than 2 unexplained miscarriages as the study group ,and 45 cases with no previous history of adverse pregnancy women of childbearing age as a control groups .Results Thyroid antibodies ATA ,TPO-Ab,TG-Ab in RSA patients were differente ,compared with the control group( P<0.05);The abortion rate in patiengts with thyroid antibodies associated with thyroid-stimulating hor-mone(TSH)≥3.93mIU was 83.33%and the abortion rate in simple thyroid antibody positive patients was 23.53%.It showed the significant difference ( P<0 .05 ) .Conclusion Thyroid autoantibodies are related to recurrent miscarriage , and TSH is elevated as a miscarriage risk factors .They are recommend as routine screening of early pregnancy .

  1. Clinical usefulness of autoantibodies to M-type phospholipase A2 receptor (PLA2R) for monitoring disease activity in idiopathic membranous nephropathy (IMN).

    Science.gov (United States)

    Radice, Antonella; Trezzi, Barbara; Maggiore, Umberto; Pregnolato, Francesca; Stellato, Tiziana; Napodano, Pietro; Rolla, Davide; Pesce, Gianpaola; D'Amico, Marco; Santoro, Domenico; Londrino, Francesco; Ravera, Federica; Ortisi, Giuseppe; Sinico, Renato Alberto

    2016-02-01

    Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (IMN). They can differentiate IMN from other glomerular diseases and primary from secondary forms of MN. Preliminary data suggest that anti-PLA2R antibody titer correlates with disease activity but more solid evidence is needed. To evaluate the performance of anti-PLA2R antibody for monitoring nephropathy activity, 149 anti-PLA2R antibody measurements were performed during the follow-up of 42 biopsy proven IMN consecutive patients. Patients were enrolled either at time of diagnosis (33 cases, inception cohort) or after diagnosis (9 patients, non-inception cohort). Anti-PLA2R detection was performed using the highly sensitive transfected cell-based indirect immunofluorescence (IIFT). Over the follow-up there was a linear time-trend of decreasing proteinuria (P<0.001), increasing serum albumin (P<0.001) and decreasing PLA2R antibody levels (P=0.002). There was a statistically significant association between changes in PLA2R antibody levels and the clinical course of PLA2R-positive IMN. The positive PLA2R serum antibody status was linearly associated with increasing proteinuria and decreasing serum albumin over time, compared with negative antibody status. Moreover, the strong correlation between the clinical conditions and PLA2R antibody levels allowed the prediction of prevalence distribution of patients with active disease, partial and complete remission. Over the course of the follow-up, the probability of halving proteinuria increased 6.5 times after disappearance of PLA2R antibodies. Our data suggest that the serial evaluation of anti-PLA2R antibodies could help in optimal timing and duration of the immunosuppressive therapy, reducing over(under)-treatment and associated side-effects. PMID:26527329

  2. Autoantibody Profiles in Collagen Disease Patients with Interstitial Lung Disease (ILD): Antibodies to Major Histocompatibility Complex Class I-Related Chain A (MICA) as Markers of ILD.

    Science.gov (United States)

    Furukawa, Hiroshi; Oka, Shomi; Shimada, Kota; Masuo, Kiyoe; Nakajima, Fumiaki; Funano, Shunichi; Tanaka, Yuki; Komiya, Akiko; Fukui, Naoshi; Sawasaki, Tatsuya; Tadokoro, Kenji; Nose, Masato; Tsuchiya, Naoyuki; Tohma, Shigeto

    2015-01-01

    Interstitial lung disease (ILD) is frequently associated with collagen disease. It is then designated as collagen vascular disease-associated ILD (CVD-ILD), and influences patients' prognosis. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in patients with collagen disease is quite poor. Here, we report our investigation of auto-antibody (Ab) profiles to determine whether they may be useful in diagnosing CVD-ILD or AoDILD in collagen disease. Auto-Ab profiles were analyzed using the Lambda Array Beads Multi-Analyte System, granulocyte immunofluorescence test, Proto-Array Human Protein Microarray, AlphaScreen assay, and glutathione S-transferase capture enzyme-linked immunosorbent assay in 34 patients with rheumatoid arthritis (RA) with or without CVD-ILD and in 15 patients with collagen disease with AoDILD. The average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels were higher in RA patients with CVD-ILD than in those without (P = 0.0013). The ratio of the average anti-MICA Ab level to the average anti-human leukocyte antigen class I Ab level (ie, MICA/Class I) was significantly higher in RA patients with CVD-ILD compared with those without (P = 4.47 × 10(-5)). To the best of our knowledge, this is the first report of auto-Ab profiles in CVD-ILD. The MICA/Class I ratio could be a better marker for diagnosing CVD-ILD than KL-6 (Krebs von den lungen-6). PMID:26327779

  3. Caspase-1-independent IL-1 release mediates blister formation in autoantibody-induced tissue injury through modulation of endothelial adhesion molecules.

    Science.gov (United States)

    Sadeghi, Hengameh; Lockmann, Anike; Hund, Anna-Carina; Samavedam, Unni K S R L; Pipi, Elena; Vafia, Katerina; Hauenschild, Eva; Kalies, Kathrin; Pas, Hendri H; Jonkman, Marcel F; Iwata, Hiroaki; Recke, Andreas; Schön, Michael P; Zillikens, Detlef; Schmidt, Enno; Ludwig, Ralf J

    2015-04-15

    Although reports documented aberrant cytokine expression in autoimmune bullous dermatoses (AIBDs), cytokine-targeting therapies have not been established in these disorders. We showed previously that IL-6 treatment protected against tissue destruction in experimental epidermolysis bullosa acquisita (EBA), an AIBD caused by autoantibodies to type VII collagen (COL7). The anti-inflammatory effects of IL-6 were mediated by induction of IL-1ra, and prophylactic IL-1ra administration prevented blistering. In this article, we demonstrate elevated serum concentrations of IL-1β in both mice with experimental EBA induced by injection of anti-COL7 IgG and in EBA patients. Increased IL-1α and IL-1β expression also was observed in the skin of anti-COL7 IgG-injected wild-type mice compared with the significantly less diseased IL-1R-deficient or wild-type mice treated with the IL-1R antagonist anakinra or anti-IL-1β. These findings suggested that IL-1 contributed to recruitment of inflammatory cells into the skin. Accordingly, the expression of ICAM-1 was decreased in IL-1R-deficient and anakinra-treated mice injected with anti-COL7. This effect appeared to be specifically attributable to IL-1 because anakinra blocked the upregulation of different endothelial adhesion molecules on IL-1-stimulated, but not on TNF-α-stimulated, cultured endothelial cells. Interestingly, injection of caspase-1/11-deficient mice with anti-COL7 IgG led to the same extent of skin lesions as in wild-type mice. Collectively, our data suggest that IL-1, independently of caspase-1, contributes to the pathogenesis of EBA. Because anti-IL-1β in a prophylactic setting and anakinra in a quasi-therapeutic setting (i.e., when skin lesions had already developed) improved experimental EBA, IL-1 appears to be a potential therapeutic target for EBA and related AIBDs. PMID:25795756

  4. Prevalence of autoantibodies in a group of hereditary angioedema patients Prevalência de autoanticorpos em uma população com angioedema hereditário

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    Sergio Duarte Dortas Junior

    2012-04-01

    Full Text Available Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.O Angioedema Hereditário é uma doença autossômica dominante. A pesquisa de rotina para autoanticorpos não é recomendada para pacientes com Angioedema Hereditário; entretanto, a prevalência desses anticorpos em pacientes com Angioedema Hereditário não está bem documentada. Objetivamos determinar a prevalência de autoanticorpos para identificar indivíduos sob risco de desenvolver doenças autoimunes. Quinze pacientes com Angioedema Hereditário atendidos no Hospital Universitário Clementino Fraga Filho aceitaram participar do estudo. A prevalência de autoanticorpos foi de 40%. Nossos dados indicam alta prevalência de autoanticorpos em pacientes com Angioedema Hereditário. Estudos de maior escala deveriam ser considerados para determinar a significância desses autoanticorpos no acompanhamento clínico de pacientes com Angioedema Hereditário.

  5. β1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Yunhui Du

    Full Text Available BACKGROUND: Autoantibodies against the second extracellular loop of the β(1-adrenergic receptor (β(1-AA not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the β(1-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β(1-AA isolated from the sera of dilated cardiomyopathy (DCM patients caused the proliferation of T cells and the secretion of cytokines. METHODS: Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and β(1-AA was detected using ELISA. The CD3(+T lymphocytes were selected separately through flow cytometry and the effect of β(1-AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK. RESULTS: β(1-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β(1-adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of β(1-AA. β(1-AA also inhibited the secretion of interferon-γ (IFN-γ while promoting an increase in interleukin-4 (IL-4 levels. CONCLUSIONS: These results demonstrate that β(1-AA isolated from DCM patients binds to β(1-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β(1-AR/cAMP/PKA and p38 MAPK pathways.

  6. Pre-transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post-kidney transplantation.

    Science.gov (United States)

    Gupta, Gaurav; Fattah, Hasan; Ayalon, Rivka; Kidd, Jason; Gehr, Todd; Quintana, Luis F; Kimball, Pamela; Sadruddin, Salima; Massey, H Davis; Kumar, Dhiren; King, Anne L; Beck, Laurence H

    2016-04-01

    Previous studies that have assessed the association of pre-transplant antiphospholipase A2 receptor autoantibody (PLA2R-Ab) concentration with a recurrence of membranous nephropathy (rMN) post-kidney transplant have yielded variable results. We tested 16 consecutive transplant patients with a history of iMN for pre-transplant PLA2R-Ab. Enzyme-linked immunosorbent assay titers (Euroimmun, NJ, USA) >14 RU/mL were considered positive. A receiver operating characteristic (ROC) analysis was performed after combining data from Quintana et al. (n = 21; Transplantation February 2015) to determine a PLA2R-Ab concentration which could predict rMN. Six of 16 (37%) patients had biopsy-proven rMN at a median of 3.2 yr post-transplant. Of these, five of six (83%) had a positive PLA2R-Ab pre-transplant with a median of 82 RU/mL (range = 31-1500). The only patient who had rMN with negative PLA2R-Ab was later diagnosed with B-cell lymphoma. One hundred percent (n = 10) of patients with no evidence of rMN (median follow-up = five yr) had negative pre-transplant PLA2R-Ab. In a combined ROC analysis (n = 37), a pre-transplant PLA2R-Ab > 29 RU/mL predicted rMN with a sensitivity of 85% and a specificity of 92%. Pre-transplant PLA2R-Ab could be a useful tool for the prediction of rMN. Patients with rMN in the absence of PLA2R-Ab should be screened for occult malignancy and/or alternate antigens. PMID:26854647

  7. High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.

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    Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus

    2016-04-01

    Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g.MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (pvalues <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392-411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. PMID:26831522

  8. Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

    International Nuclear Information System (INIS)

    We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2-A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging

  9. Validation of a rapid type 1 diabetes autoantibody screening assay for community-based screening of organ donors to identify subjects at increased risk for the disease.

    Science.gov (United States)

    Wasserfall, C; Montgomery, E; Yu, L; Michels, A; Gianani, R; Pugliese, A; Nierras, C; Kaddis, J S; Schatz, D A; Bonifacio, E; Atkinson, M A

    2016-07-01

    The Network for Pancreatic Organ donors with Diabetes (nPOD) programme was developed in response to an unmet research need for human pancreatic tissue obtained from individuals with type 1 diabetes mellitus and people at increased risk [i.e. autoantibody (AAb)-positive] for the disease. This necessitated the establishment of a type 1 diabetes-specific AAb screening platform for organ procurement organizations (OPOs). Assay protocols for commercially available enzyme-linked immunosorbent assays (elisas) determining AAb against glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA-2A) and zinc transporter-8 (ZnT8A) were modified to identify AAb-positive donors within strict time requirements associated with organ donation programmes. These rapid elisas were evaluated by the international islet AAb standardization programme (IASP) and used by OPO laboratories as an adjunct to routine serological tests evaluating donors for organ transplantation. The rapid elisas performed well in three IASPs (2011, 2013, 2015) with 98-100% specificity for all three assays, including sensitivities of 64-82% (GADA), 60-64% (IA-2A) and 62-68% (ZnT8A). Since 2009, nPOD has screened 4442 organ donors by rapid elisa; 250 (5·6%) were identified as positive for one AAb and 14 (0.3%) for multiple AAb with 20 of these cases received by nPOD for follow-up studies (14 GADA+, two IA-2A(+) , four multiple AAb-positive). Rapid screening for type 1 diabetes-associated AAb in organ donors is feasible, allowing for identification of non-diabetic, high-risk individuals and procurement of valuable tissues for natural history studies of this disease. PMID:27029857

  10. Pokemon自身抗体在原发性肝癌中的表达及意义%The prevalence of autoantibodies against Pokemon in hepatocellular carcinoma and its significance

    Institute of Scientific and Technical Information of China (English)

    吴阳; 吴大帅; 张弓; 赵永福; 赵龙拴; 张水军

    2013-01-01

    Objective To investigate the prevalence of autoantibodies against Pokemon in hepatocellular carcinoma (HCC) and its significance as a serological diagnostic biomarker.Methods Recombinant Pokemon protein was expressed from E.coli BL21 (E3) and was purified using nickel column chromatography.The antigenicity of the purified Pokemon protein was performed by Western blotting.Autoantibody responses to Pokemon were evaluated by enzyme-linked immunosorbent assay (ELlSA) in sera from 142 patients with HCC,28 with liver cirrhosis (LC) and 30 with chronic hepatitis (CH),as well as from 96 normal human individuals.Results The antigenicity of the purified Pokemon protein was confirmed and the recombinant Pokemon was able be used as coated protein in ELISA assay.The prevalence of autoantibodies against Pokemon was 49% (69/142) in HCC,which was significantly higher than that in LC (0),CH (0) and normal hnman sera(0) (NHS; P <0.01).The average titer of autoantibodies against Pokemon in HCC sera(0.51 ±0.03) was higher compared to that in LC (0.16 ±0.03),CH (0.18 ±0.05) and NHS(0.17 ± 0.01) (P < 0.01).When both autoantibodies against Pokemon and alpha fetal protein (AFP) were used simultaneously as diagnostic markers,sensitivity reached 71.12%.Conclusion Anti-Pokemon autoantibodies may be potential diagnostic markers for HCC,especially in conjunction with AFP.%目的 探讨Pokemon白身抗体在原发性肝癌(Hcc)中的表达及其作为诊断标志物的意义.方法 应用BL2l(E3)大肠杆菌表达并经镍柱纯化Pokemon抗体,Western blot证实具有免疫原性,应用酶联免疫吸附试验(ELISA)方法筛选142例HCC 、30例慢性肝炎、28例肝硬化及96例正常人血清中Pokemon自身抗体的表达水平,并与甲胎蛋白(AFP)水平比较.结果 纯化的Pokemon蛋白能够被特异抗体识别.HCC中抗Pokemon抗体阳性率(49%)显著高于肝炎(0)、肝硬化患者(0)及正常人(0)(P<0.01).HCC中抗Pokemon抗体的平均滴度(0.51±0.03)

  11. Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1 antigens and development of two novel ELISAs with different diagnostic performances in idiopathic membranous nephropathy.

    Science.gov (United States)

    Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Tomas, Nicola M; Lochouarn, Marine; Jeammet, Louise; Mariat, Christophe; Krummel, Thierry; Burtey, Stéphane; Courivaud, Cécile; Schlumberger, Wolfgang; Zorzi, Kévin; Benzaken, Sylvia; Bernard, Ghislaine; Esnault, Vincent L M; Lambeau, Gérard

    2015-11-01

    About 70% of patients with idiopathic membranous nephropathy (iMN) have autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m) PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active disease or in drug-induced remission. In contrast, only 51% of patients were reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti-PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1 orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an independent predictor of clinical outcome in multivariate analysis (p = 0.009), and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of patients (12 patients) had a poor renal outcome (p 605 RU/mL) only in iMN patients at risk of poor prognosis, and is thus useful to predict iMN outcome. PMID:26296473

  12. Monozygotic twin pairs discordant for Hashimoto's thyroiditis share a high proportion of thyroid peroxidase autoantibodies to the immunodominant region A. Further evidence for genetic transmission of epitopic “fingerprints”

    DEFF Research Database (Denmark)

    Brix, Thomas Heiberg; Hegedüs, Laszlo; Gardas, Andrzej; Banga, J Paul; Nielsen, Claus H

    2010-01-01

    Thyroid peroxidase antibodies (TPOAbs) in patients with Hashimoto's thyroiditis (HT) predominantly react with two immunodominant regions (IDR-A, IDR-B). Theoretically, as shown for the level of TPOAbs, the autoantibody epitopic recognition of the IDRs could be under genetic control. To examine this......, we compared the distribution of TPOAb epitopic fingerprints between healthy monozygotic (MZ) co-twins and siblings to patients with clinically overt HT with a control group of euthyroid subjects, matched for sex and age, but without autoimmune thyroid disease (AITD) among their first-degree relatives...

  13. Anti-A2/RA33 autoantibodies are directed to the RNA binding region of the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. Differential epitope recognition in rheumatoid arthritis, systemic lupus erythematosus, and mixed connective tissue disease.

    OpenAIRE

    Skriner, K; Sommergruber, W H; Tremmel, V; Fischer, I; Barta, A; Smolen, J S; Steiner, G

    1997-01-01

    The recently described anti-A2/RA33 autoantibodies occur in 20-40% of patients with RA, SLE, and mixed connective tissue disease (MCTD). They are directed to the A2 protein of the heterogeneous nuclear ribonucleoprotein complex (hnRNP-A2), an abundant nuclear protein associated with the spliceosome. The NH2-terminal half of the antigen contains two conserved RNA binding domains whereas its COOH-terminal part is extremely glycine-rich. The aim of this study was to characterize the autoepitopes...

  14. Association of adiponectin, interleukin (IL)-1ra, inducible protein 10, IL-6 and number of islet autoantibodies with progression patterns of type 1 diabetes the first year after diagnosis

    DEFF Research Database (Denmark)

    Kaas, A; Pfleger, Claudia Christina; Hansen, Lene;

    2010-01-01

    The progression of type 1 diabetes after diagnosis is poorly understood. Our aim was to assess the relation of disease progression of juvenile-onset type 1 diabetes, determined by preserved beta cell function the first year after diagnosis, with systemic cytokine concentrations and number of...... patients (P = 0·03 and P = 0·006). IL-1ra, IP-10 and IL-6 did not differ between the groups at any time-point. The number of autoantibodies differed significantly between the groups at 1 month (P = 0·04), where rapid progressers had the largest number. There was no difference between the groups in human...

  15. Anti-interleukin-1 alpha autoantibodies in humans: Characterization, isotype distribution, and receptor-binding inhibition--higher frequency in Schnitzler's syndrome (urticaria and macroglobulinemia)

    International Nuclear Information System (INIS)

    Since autoantibodies (Abs) to cytokines may modify their biologic activities, high-affinity binding factors for interleukin-1 alpha (IL-1 alpha BF) were characterized in human sera. IL-1 alpha BF was identified as IgG (1) by sucrose density-gradient centrifugation followed by immunodiffusion autoradiography, (2) by ligand-blotting method, (3) by ligand binding to affinity-immobilized serum IgG, and (4) by IgG affinity purification followed by sucrose density-gradient centrifugation. IL-1 alpha binding activity resided in the F(ab)2 fragment. The apparent equilibrium constant was in the range of IgG found after immunization with conventional antigens (i.e., 10(-9) to 10(-10) mol/L). Anti-IL-1 alpha IgG auto-Abs represented only an extremely small fraction of total IgG (less than 1/10(-5)). Some sera with IL-1 alpha BF and purified IgG thereof were able to inhibit by 96% to 98% the binding of human recombinant IL-1 alpha to its receptor on murine thymoma EL4-6.1 cells, whereas other sera did not. When 125I-labeled anti-IL-1 alpha IgG complexes were injected into rats, they prolonged the plasma half-life of 125I-labeled IL-1 alpha several fold and altered its tissue distribution. The predominant class was IgG (12/19), mainly IgG4 (9/19), but in five of the sera, anti-IL-1 alpha IgA was also detected. In a screening of 271 sera, IL-1 alpha BF was detected in 17/98 normal subjects and was not more frequent in several control groups of patients, except in patients with Schnitzler's syndrome (fever, chronic urticaria, bone pain, and monoclonal IgM paraprotein) (6/9; p less than 0.005). The pathologic significance of these auto-Abs remains to be determined

  16. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus.

    Science.gov (United States)

    Saariaho, Anna-Helena; Vuorela, Arja; Freitag, Tobias L; Pizza, Fabio; Plazzi, Giuseppe; Partinen, Markku; Vaarala, Outi; Meri, Seppo

    2015-09-01

    Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination. PMID

  17. The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

    Directory of Open Access Journals (Sweden)

    Kvido Smitka

    2013-01-01

    Full Text Available Eating disorders such as anorexia (AN and bulimia nervosa (BN are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY, peptide YY (PYY, cholecystokinin (CCK, leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE, serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

  18. Autoantibody frequency in celiac disease

    Directory of Open Access Journals (Sweden)

    Erkan Caglar

    2009-01-01

    Full Text Available AIM: In our study, we investigated the levels of glutamic acid decarboxylase antibody (anti-GAD, islet cell antibody (ICA, thyroperoxidase antibody (anti-TPO, thyroglobulin antibody (anti-TG, antinuclear antibodies (FANA, antibodies to double-stranded DNA (anti-ds DNA, antibody to Sjögren syndrome A antigen (anti-SSA, antibody to Sjögren syndrome B antigen (anti-SSB, Smith antibody (anti-Sm, smooth muscle antibodies (ASMA, and antimitochondrial antibody liver-kidney microsome (AMA-LKM in patients with celiac disease as compared to healthy controls and autoimmune hypothyroid patients. MATERIALS AND METHODS: A total of 31 patients with celiac disease, 34 patients with autoimmune hypothyroidism and 29 healthy subjects were included in this study. Anti-SSA, anti-SSB, anti-Sm, anti-ds DNA, anti-GAD, anti-TPO and anti-TG were studied by Enzyme-Linked Immunosorbent Assay (ELISA, and AMA-LKM, ASMA, ANA and ICA were studied by immunofluorescence. Clinical data and the results of free thyroxine-thyroid stimulating hormone (FT4-TSH were collected from the patients' files by retrospective analysis. SPSS ver 13.0 was used for data analysis, and the χ2 method was used for comparisons within groups. RESULTS: The frequency of anti-SSA, anti-SSB, anti-GAD, anti-Sm, anti-ds DNA, AMA-LKM, ASMA, ANA and ICA were not significantly different between the groups. Levels of anti-TPO and anti-TG antibodies were found to be significantly higher (<0.001 in autoimmune hypothyroid patients when compared with other groups. CONCLUSION: In previous studies, an increased frequency of autoimmune diseases of other systems has been reported in patients with celiac disease. We found that the frequency of autoimmune antibodies specific for other autoimmune diseases was not higher in celiac disease.

  19. Autoantibody Frequency in Celiac Disease

    OpenAIRE

    Erkan Caglar; Serdal Ugurlu; Aliye Ozenoglu,; Gunay Can,; Pinar Kadioglu; Ahmet Dobrucali

    2009-01-01

    AIM: In our study, we investigated the levels of glutamic acid decarboxylase antibody (anti-GAD), islet cell antibody (ICA), thyroperoxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), antinuclear antibodies (FANA), antibodies to double-stranded DNA (anti-ds DNA), antibody to Sjögren syndrome A antigen (anti-SSA), antibody to Sjögren syndrome B antigen (anti-SSB), Smith antibody (anti-Sm), smooth muscle antibodies (ASMA), and antimitochondrial antibody liver-kidney microsome (AMA-L...

  20. Glutamic acid decarboxylase 65 and islet cell antigen 512/IA-2 autoantibodies in relation to human leukocyte antigen class II DR and DQ alleles and haplotypes in type 1 diabetes mellitus.

    Science.gov (United States)

    Stayoussef, Mouna; Benmansour, Jihen; Al-Jenaidi, Fayza A; Said, Hichem B; Rayana, Chiheb B; Mahjoub, Touhami; Almawi, Wassim Y

    2011-06-01

    The frequencies of autoantibodies against glutamic acid decarboxylase 65 (GAD65) and islet cell antigen (ICA) 512/IA-2 (512/IA-2) are functions of the specific human leukocyte antigen (HLA) in type 1 diabetes mellitus (T1D). We investigated the association of HLA class II (DR and DQ) alleles and haplotypes with the presence of GAD and IA-2 autoantibodies in T1D. Autoantibodies were tested in 88 Tunisian T1D patients and 112 age- and gender-matched normoglycemic control subjects by enzyme immunoassay. Among T1D patients, mean anti-GAD antibody titers were higher in the DRB1*030101 allele (P < 0.001), together with the DRB1*030101/DQB1*0201 (P < 0.001) and DRB1*040101/DQB1*0302 (P = 0.002) haplotypes, while lower anti-GAD titers were associated with the DRB1*070101 (P = 0.001) and DRB1*110101 (P < 0.001) alleles and DRB1*070101/DQB1*0201 (P = 0.001) and DRB1*110101/DQB1*030101 (P = 0.001) haplotypes. Mean anti-IA-2 antibody titers were higher in the DRB1*040101 allele (P = 0.007) and DRB1*040101/DQB1*0302 (P = 0.001) haplotypes but were lower in the DRB1*110101 allele (P = 0.010) and the DRB1*110101 (P < 0.001) and DRB1*110101/DQB1*030101 (P = 0.025) haplotypes. Multinomial regression analysis confirmed the positive association of DRB1*030101 and the negative association of DRB1*110101 and DQB1*030101, along with the DRB1*070101/DQB1*0201 and DRB1*110101/DQB1*030101 haplotypes, with anti-GAD levels. In contrast, only the DRB1*040101/DQB1*0302 haplotype was positively associated with altered anti-IA-2 titers. Increased GAD65 and IA-2 antibody positivity is differentially associated with select HLA class II alleles and haplotypes, confirming the heterogeneous nature of T1D. PMID:21490167