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Sample records for autoantibodies

  1. [Autoantibodies].

    Science.gov (United States)

    Ishihara, Yasushi

    2005-06-01

    The autoantibody test gives significant information for diagnosis of autoimmune diseases. Since the finding of the LE-cell in 1948, dozens of autoantibodies have been found. Anti nuclear antibody (ANA) is the essential test for the screening of autoantibodies. Indirect immunofluorescence (IIF) is the conventional method for the detection of ANA. IIF can detect a wide spectrum of ANA and gives abundant information obtained from a staining pattern. However under the recent circumstances of using advanced fluorescent microscopes and reagents we often have difficulty interpreting positive results seen in normal individuals and in detailed staining patterns. ELISA (enzyme-linked immunosorbent assay), detecting disease specific autoantibodies alone, is one solution. Some antibodies such as anti-DNA or anti-ENA (extractable nuclear antigen) have a strong relation to specific diseases. These autoantibodies have been detected by IIF, RIA (radioimmunoassay) or DID (double immune diffusion). With the progress of molecular biology many autoantigens have been characterized. Now ELISA is a typical way to detect autoantibodies because purified or recombinant antigens are easily available. Though RF (rheumatoid factor) is the historical autoantibody detected in RA patients, the specificity to RA is low. The new anti-CCP is promising from its high specificity and sensitivity. Now we can choose various kind of autoantibody tests, not only conventional ones but also newly developed ones. For diagnosis and treatment of autoimmune diseases, understanding of both clinical significance and methodology is important.

  2. Autoantibody standardization in The Netherlands.

    NARCIS (Netherlands)

    Damoiseaux, J.; Tervaert, J.W.; Derksen, R.; Hamann, D.; Hooijkaas, H.; Klasen, I.S.; Kallenberg, C.; Limburg, P.; Smeenk, R.

    2009-01-01

    Several initiatives have been undertaken, independent of the European Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in The Netherlands. The Dutch EASI team has made an inventory of which initiatives on autoantibody standardization are already available and what future

  3. Autoantibodies in Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    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.

  5. Autoantibody Production in Rabbits

    Science.gov (United States)

    Asherson, G. L.; Rose, M. Elaine

    1963-01-01

    The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14, 21 and 28 days after infection. The factors were regarded as antibodies because they behaved as macroglobulins on diethylaminoethyl—cellulose chromatography and sucrose gradient centrifugation, and as autoantibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with high activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. PMID:13965167

  6. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

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

    1985-01-01

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

  7. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk

    2012-01-01

    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  8. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  9. TSH RECEPTOR AUTOANTIBODIES

    Science.gov (United States)

    Michalek, Krzysztof; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2009-01-01

    Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves’ disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs. PMID:19332151

  10. [Hashimoto's encephalopathy and autoantibodies].

    Science.gov (United States)

    Yoneda, Makoto

    2013-04-01

    Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of

  11. Autoantibody Profile in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    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.

  12. Autoantibodies in primary sclerosing cholangitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Roksund Hov; Kirsten Muri Boberg; Tom H Karlsen

    2008-01-01

    The aetiology of primary sclerosing cholangitis (PSC)is not known and controversy exists as to whether PSC should be denominated an autoimmune disease.A large number of autoantibodies have been detected in PSC patients,but the specificity of these antibodies is generally low,and the frequencies vary largely between different studies.The presence of autoantibodies in PSC may be the result of a nonspecific dysregulation of the immune system,but the literature in PSC points to the possible presence of specific antibody targets in the biliary epithelium and in neutrophil granulocytes.The present review aims to give an overview of the studies of autoantibodies in PSC,with a particular emphasis on the prevalence,clinical relevance and possible pathogenetic importance of each individual marker.

  13. Autoantibodies in Patients with Fasciolosis

    Directory of Open Access Journals (Sweden)

    M Korkmaz

    2009-07-01

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

  14. 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

  15. 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…

  16. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  17. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley

    2015-11-01

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

  18. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

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    Agata N. Burska

    2014-01-01

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

  19. Therapeutic implications of autoantibodies in rheumatoid arthritis

    OpenAIRE

    Aletaha, Daniel; Blüml, Stephan

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the presence of autoantibodies. Their value for diagnostic/prognostic purposes has been well established. In contrast, their role in established disease and their associations with disease activity is less clear. Moreover, as evidence is accumulating that these autoantibodies are causally involved in certain key aspects of the disease, such as the initiation and perpetuation of joint inflammation or join destruction, ...

  20. 21 CFR 866.5870 - Thyroid autoantibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's...

  1. Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2007-01-01

    Purpose of reviews This review focuses on recent advance in the diagnosis pathogenesis and treatment of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Recent findings Antineutrophil cytoplasmic autoantibodies are closely associated with Wegener's granulomatosis and micro

  2. 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

  3. Autoantibodies in SLE: Specificities, Isotypes and Receptors

    Directory of Open Access Journals (Sweden)

    Barbara Dema

    2016-01-01

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

  4. Autoantibody profiling in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Xia, Yang; Kellems, Rodney E

    2013-06-21

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

  6. Incidence of Autoantibodies to C1Q Complement Component in Women with Miscarriages and Autoantibodies to Phospholipids and Chorionic Gonadotropin.

    Science.gov (United States)

    Menzhinskaya, I V; Van'ko, L V; Kashentseva, M M; Kiryushchenkov, P A; Sukhikh, G T

    2015-12-01

    Autoantibodies to C1q complement component are often detected in patients with autoimmune diseases. The complement system is involved in the pathophysiology of gestosis. The incidence of anti-C1q autoantibodies was studied in women with miscarriages and autoantibodies to phospholipids and chorionic gonadotropin. Serum C3 and C4 complement components and anti-C1Q autoantibodies (IgG) were measured by ELISA. The median levels of C3 and C4 in patients with miscarriages were lower than in healthy women. Anti-C1q autoantibodies were more often found in the patients than in controls; patients with autoantibodies to phospholipids formed a risk group. Median levels of anti-C1q autoantibodies were higher in the patients with autoantibodies to phospholipids and chorionic gonadotropin than in healthy women. Hence, activation of the complement system and hyperproduction of anti-C1q autoantibodies were unfolding in patients with miscarriages, mainly in the patients with autoantibodies to phospholipids.

  7. 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.

  8. [Stiff-person syndrome and related autoantibodies].

    Science.gov (United States)

    Tomioka, Ryo; Tanaka, Keiko

    2013-04-01

    Central nervous system hyperexcitability disorders, known as stiff-man/person syndrome (SPS), are thought to be related to the regulatory disturbance of inhibitory synaptic transmission of motor neurons in the brainstem and spinal cord. SPS is characterized by stiffness and spasms of the axis and limbs and is divided into two clinical subgroups: classic SPS, which affects the lumbar, trunk, and proximal limb muscles, and SPS-plus syndrome. The latter comprises (1) the stiff-limb subtype, in which symptom is limited to the lower limbs; (2) jerking stiff-man syndrome, characterized by chronically progressive stiffness and myoclonus; and (3) acute-onset and progressive encephalomyelitis with rigidity and myoclonus. Almost 80% of patients with classic SPS harbor autoantibodies against glutamic acid decarboxylase 65 (GAD65). In approximately 30-40% of patients, SPS accompanies type I diabetes, and anti-GAD65 antibodies are detected frequently in type I diabetes. However, the antibody-recognizing epitopes might be different between SPS and diabetes. Other autoantibodies against glycine receptor α1 (12% of patients with SPS) and GABA(A)-receptor associated protein (70% of patients with SPS) have been reported. In paraneoplastic SPS, anti-amphiphysin antibodies have been shown in patients with breast cancer or small cell lung cancer. One case of mediastinal tumor with anti-gephyrin antibodies has also been reported. However, the roles of these autoantibodies in the pathomechanisms of SPS have not yet been elucidated.

  9. [Autoantibodies to glutamate and GABA in opiate addiction].

    Science.gov (United States)

    Vetrile, L A; Fomina, V G; Nevidimova, T I; Vetlugina, T P; Batukhtina, E I; Savochkina, D N; Zakharova, I A; Davydova, T V

    2015-01-01

    Blood serum from 129 patients with opium addiction at different stages of the disease and 63 donors (control group) was examined for the presence of autoantibodies to the exciting and inhibitory amino acids glutamate and GABA. It was shown enhanced production of autoantibodies to glutamate and GABA. Dependence of the level and frequency of detec- tion of autoantibodies to glutamate and GABA on the stage of the disease was revealed.

  10. Autoantibody Standardization in the Netherlands The Past, the Present, and the Future

    NARCIS (Netherlands)

    Damoiseaux, Jan; Tervaert, Jan Willem Cohen; Derksen, Ronald; Hamann, Dorte; Hooijkaas, Herbert; Klasen, Ina; Kallenberg, Cees; Limburg, Pieter; Smeenk, Ruud; Shoenfeld, Y; Gershwin, ME

    2009-01-01

    Several initiatives have been undertaken, independent of the European Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in the Netherlands. The Dutch EASI team has made an inventory of which initiatives on autoantibody standardization are already available and what future

  11. 21 CFR 866.5660 - Multiple autoantibodies immunological test system.

    Science.gov (United States)

    2010-04-01

    .... Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

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

    OpenAIRE

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

    2014-01-01

    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 perfor...

  13. Regulatory and pathogenetic mechanisms of autoantibodies in SLE

    NARCIS (Netherlands)

    Radic, M.; Herrmann, M.; Vlag, J. van der; Rekvig, O.P.

    2011-01-01

    In the 53 years since the discovery of anti-DNA autoantibodies in lupus [1, 2, 3] , recalcitrant questions have been pondered and possible answers have been debated. The discovery of anti-DNA autoantibodies presented many puzzles: How is immunological tolerance to native B-form DNA broken? What elic

  14. 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…

  15. 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)....

  16. Autoantibody recognition mechanisms of MUC1

    Science.gov (United States)

    Phillips, J. C.

    2017-03-01

    The most cost-effective blood-based, noninvasive molecular early cancer biomarkers are based on p53 epitopes and MUC1 tandem repeats. Here we use dimensionally compressed bioinformatic fractal scaling analysis to compare the two distinct and comparable probes, which examine different sections of the autoantibody population, achieving combined sensitivities of order 50%. We explain the experimental observation that glycosylation does not enhance, and can depress, the sensitivity of MUC1 tandem repeat biomarkers. We propose a possible supplementary MUC1 epitope in the SEA region outside the tandem repeats.

  17. 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

  18. 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...... the upper reference limit of the laboratory (6 had TPOAb >10 kIU/L, 6 had TgAb >20 kIU/L and 1 had TRAb >0.75 IU/L). Eight women had Tg below the lower reference limit, five of whom had elevated TgAb. Variations in the thyroid antibodies were random and not related to the menstrual cycle. For TPOAb (2...

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Pancreatic autoantibodies after pancreas-kidney transplantation - do they matter?

    Science.gov (United States)

    Martins, La Salete; Henriques, Antonio C; Fonseca, Isabel M; Rodrigues, Anabela S; Oliverira, José C; Dores, Jorge M; Dias, Leonidio S; Cabrita, Antonio M; Silva, José D; Noronha, Irene L

    2014-04-01

    Type 1 diabetes recurrence has been documented in simultaneous pancreas-kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow-up (maximum 138 months), 43.8% of patients were positive (from pre-transplant or after recurrence) for at least one autoantibody - the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti-insulin (8.6%) and anti-islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C-peptide levels, and a higher number of HLA-matches. Analyzing the sample divided into four groups according to pre-/post-transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C-peptide levels. Positivity for these autoantibodies pre-transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody-positive SPKT is a matter of concern, which deserves further attention.

  4. Antineutrophil cytoplasmic autoantibodies in ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Vodjgani M

    2000-10-01

    Full Text Available Antineutrophil cytoplasmic autoanibodies (ANCA were detecte in patients with certain autoimmune vascular disease such as Wegner’s granulomatosis, polyarthrits nodosa and systemic luuc erythematous. Indirect immunofluorescence (IIF technique was employed to detec these autoantibodies.ANCA have been recently detected in some forms of inflammatory bowel disease (IBD, ulcerative colitis (U.C. Crohn’s disease (C.D and primary sclerosing cholangitis (PSC. By IIF method, two general patterns of ANCA were seen: a cytoplasmic (C-ANCA and perinuclear form (P-ANCA. In this study we evaluated the presece of ANCA in 52 U.C. patients and 69 matched normal control group by IIF technique, and it’s relationship with disease activity. Site of colon involvement and, lesion extent. The results showed that all control group were ANCA negative, but 58% of patients had ANCA, and most cases (70% had C- ANCA. The obtained results also revealed that there was no relationship between ANCA and disease activity

  5. Regulatory and pathogenetic mechanisms of autoantibodies in SLE.

    Science.gov (United States)

    Radic, Marko; Herrmann, Martin; van der Vlag, Johan; Rekvig, Ole Petter

    2011-08-01

    In the 53 years since the discovery of anti-DNA autoantibodies in lupus [1, 2, 3] , recalcitrant questions have been pondered and possible answers have been debated. The discovery of anti-DNA autoantibodies presented many puzzles: How is immunological tolerance to native B-form DNA broken? What elicits characteristic systemic lupus erythematosus (SLE) autoantibodies? Which of the diverse anti-nuclear reactivities are pathogenic? What is the role of autoantibodies in the clinical presentation of disease? How do genetic predisposition and environmental triggers contribute to SLE? These questions were brought into focus by Professor David Stollar in an introductory presentation to an intense, three-day meeting set among the rugged and inspiring scenery of the Norwegian arctic coastline (the Scientific Program is included as supplemental File 1). Other participants presented and discussed topics directed to understanding the origin and clinico-pathological impact of autoantibodies to chromatin and phospholipid antigens. In the following, several aspects of the workshop are discussed.

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

    Directory of Open Access Journals (Sweden)

    Karol Charkiewicz

    2016-01-01

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

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

    Science.gov (United States)

    Charkiewicz, Karol; Zbucka-Kretowska, Monika; Goscik, Joanna; Wolczynski, Slawomir; Lemancewicz, Adam; Laudanski, Piotr

    2016-01-01

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

  8. NEUTROPHIL CYTOPLASMIC AUTOANTIBODIES AFTER LIVER-TRANSPLANTATION IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS

    NARCIS (Netherlands)

    Haagsma, E.B.; MULDER, A.H.L.; Gouw, A.S.H.; MEERMAN, L.; Slooff, M.JH; Kallenberg, Cees; Horst, G.

    1993-01-01

    The immunopathogenic importance of neutrophil cytoplasmic autoantibodies in ulcerative colitis and primary sclerosing cholangitis is unknown. These autoantibodies were investigated before and after liver transplantation in 9 patients with primary sclerosing cholangitis. Sera from 10 patients transpl

  9. 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

  10. 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.

  11. Autoantibodies against tumor-associated antigens fordetection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the mostcommon tumors worldwide. The survival rate after theonset of symptoms is generally less than one year forthe late presentation of HCC, and reliable tools for earlydiagnosis are lacking. Therefore, novel biomarkers forthe early detection of HCC are urgently required. Recentstudies show that the abnormal release of proteins bytumor cells can elicit humoral immune responses toself-antigens called tumor-associated antigens (TAAs).The corresponding autoantibodies can be detectedbefore the clinical diagnosis of cancer. Therefore, thereis growing interest in using serum autoantibodies ascancer biomarkers. In this review, we focus on theadvances in research on autoantibodies against TAAs asserum biomarker for detection of HCC, the mechanismof the production of TAAs, and the association ofautoantibodies with patients' clinical characteristics.

  12. Autoimmune Hemolytic Anemia and Red Blood Cell Autoantibodies.

    Science.gov (United States)

    Quist, Erin; Koepsell, Scott

    2015-11-01

    Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare, RBC autoantibodies are encountered frequently and can complicate transfusion workups, impede RBC alloantibody identification, delay distribution of compatible units, have variable clinical significance that ranges from benign to life-threatening, and may signal an underlying disease or disorder. In this review, we discuss the common presenting features of RBC autoantibodies, laboratory findings, ancillary studies that help the pathologist investigate the clinical significance of autoantibodies, and how to provide appropriate patient care and consultation for clinical colleagues. Pathologists must be mindful of, and knowledgeable about, this entity because it not only allows for direct clinical management but also can afford an opportunity to preemptively treat an otherwise silent malignancy or disorder.

  13. Thyroid Autoantibodies in Pregnancy: Their Role, Regulation and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Francis S. Balucan

    2013-01-01

    Full Text Available Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum.

  14. [Investigation of the presence of autoantibodies in patients with toxocariasis].

    Science.gov (United States)

    Kaya, Selçuk; Demirci, Mustafa; Sesli Cetin, Emel; Cicioğlu Aridoğan, Buket; Sahin, Mehmet; Taş, Tekin; Korkmaz, Metin

    2009-10-01

    Immunopathologic reactions may occur during toxocariasis due to tissue invasion and destruction by the secretions of larvae containing various enzymes with broad spectrum. The aim of this study was to search for autoantibodies such as anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (ASMA), anti-neutrophil cytoplasmic (ANCA), anti-myeloperoxidase (MPO) and liver-kidney microsomal type 1 (LKM-1) antibodies in patients with toxocariasis, in order to investigate the role of toxocariasis as a trigger factor for autoimmune reactions. Forty patients (22 were male; mean age: 35.6 +/- 10.7 years) diagnosed as toxocariasis by clinical findings (abdominal pain, allergic symptoms and/or eosinophilia, without detection of any other causative agents, and without liver dysfunction, diabetes mellitus, cardiac or renal failure, and autoimmune disease) and in-house ELISA positivity and 32 healthy controls (16 were male; mean age: 40.7 +/- 11.2 years) were included to the study. ANA (screen), dsDNA, SS-A, SS-B, Scl-70, LKM-1, MPO and M2 autoantibodies have been investigated by ELISA (Euroimmun, Germany), while ANCA, AMA and ASMA antibodies by indirect immunofluorescence (IMMCO, NY) methods. Autoantibody positivity was detected in 18 (45%) patients of whom 11 yielded a single type, and 7 yielded > or = 2 types of autoantibodies. This rate was 12.5% for control group (two subjects were positive for ANA-Screen, one for anti-M2 and one for anti-LKM-1). The difference between the total positivity rates in patient and control groups was found statistically significant (chi2 = 5.72, p = 0.004). The most frequent autoantibody type among patients were ASMA (n = 6), followed by anti-dsDNA (n = 5), anti-M2 (n = 5), anti-SS-B (n = 4), anti-LKM-1 (n = 3), anti-SS-A (n = 2), ANCA (n = 2) and anti-MPO (n = 1). Positivity rate for ASMA was found statistically significant in patients' group compared to controls (chi2 = 12.24, p = 0.03), while there was no significant difference

  15. MHC associations with clinical and autoantibody manifestations in European SLE.

    Science.gov (United States)

    Morris, D L; Fernando, M M A; Taylor, K E; Chung, S A; Nititham, J; Alarcón-Riquelme, M E; Barcellos, L F; Behrens, T W; Cotsapas, C; Gaffney, P M; Graham, R R; Pons-Estel, B A; Gregersen, P K; Harley, J B; Hauser, S L; Hom, G; Langefeld, C D; Noble, J A; Rioux, J D; Seldin, M F; Vyse, T J; Criswell, L A

    2014-04-01

    Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.

  16. Characterization and potential clinical applications of autoantibodies against cytokines

    DEFF Research Database (Denmark)

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

    2009-01-01

    Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodo...

  17. 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.

  18. Specificity of islet cell autoantibodies and coexistence with other organ specific autoantibodies in type 1 diabetes mellitus.

    Science.gov (United States)

    Tsirogianni, Alexandra; Pipi, Elena; Soufleros, Konstantinos

    2009-07-01

    Type 1 diabetes mellitus (T1DM) has been shown to be a disease characterized by immune-mediated destruction of the insulin-producing islet beta-cells (beta-cells) in the pancreas. Intensive studies, in both patients and animal models are trying to elucidate the specific antigenic targets that are responsible for islet cell autoimmunity. So far, the most important molecules that have been recognized are the native insulin, the 65-kDa form of glutamic acid decarboxylase (GAD(65)) and the insulinoma-antigen 2 (IA-2). Identification of those specific autoantibodies that are involved in the primary immunological events of the autoimmune disease process will allow the development of novel diagnostic procedures for early detection and initiation of potential therapy prior to irreversible loss of beta-cells. Within the framework of polyglandular disorders, T1DM may coexist with other organ specific autoimmune diseases such as autoimmune thyroid disease (ATD), autoimmune gastritis (AG), celiac disease (CD) and Addison's disease (AD), which are associated with the production of organ-specific autoantibodies. So, as a subset of patients with those autoantibodies will develop clinical disease, screening T1DM patients could prognosticate morbidity relative to unrecognised clinical entities. The close follow-up of patients with organ-specific autoantibodies could lead to seasonable identification of those requiring therapy.

  19. 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 ...

  20. 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.

  1. The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

    Science.gov (United States)

    Liu, Jin; Bian, Lingling; Ji, Li; Chen, Yang; Chen, Heng; Gu, Yong; Ma, Bingqin; Gu, Wei; Xu, Xinyu; Shi, Yun; Wang, Jian; Zhu, Dalong; Sun, Zilin; Ma, Jianhua; Jin, Hui; Shi, Xing; Miao, Heng; Xin, Bing; Zhu, Yan; Zhang, Zhenwen; Bu, Ruifang; Xu, Lan; Shi, Guangde; Tang, Wei; Li, Wei; Zhou, Dongmei; Liang, Jun; Cheng, Xingbo; Shi, Bimin; Dong, Jixiang; Hu, Ji; Fang, Chen; Zhong, Shao; Yu, Weinan; Lu, Weiping; Wu, Chenguang; Qian, Li; Yu, Jiancheng; Gao, Jialin; Fei, Xiaoqiang; Zhang, Qingqing; Wang, Xueqin; Cui, Shiwei; Cheng, Jinluo; Xu, Ning; Wang, Guofeng; Han, Guoqing; Xu, Chunrong; Xie, Yun; An, Minmin; Zhang, Wei; Wang, Zhixiao; Cai, Yun; Fu, Qi; Fu, Yu; Zheng, Shuai; Yang, Fan; Hu, Qingfang; Dai, Hao; Jin, Yu; Zhang, Zheng; Xu, Kuanfeng; Li, Yifan; Shen, Jie; Zhou, Hongwen; He, Wei; Zheng, Xuqin; Han, Xiao; Yu, Liping; She, Jinxiong; Zhang, Mei; Yang, Tao

    2016-09-01

    Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

  2. 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.

  3. The role of B cells and autoantibodies in neuropsychiatric lupus.

    Science.gov (United States)

    Wen, Jing; Stock, Ariel D; Chalmers, Samantha A; Putterman, Chaim

    2016-09-01

    The central nervous system manifestations of SLE (neuropsychiatric lupus, NPSLE) occur frequently, though are often difficult to diagnose and treat. Symptoms of NPSLE can be quite diverse, including chronic cognitive and emotional manifestations, as well as acute presentations, such as stroke and seizures. Although the pathogenesis of NPSLE has yet to be well characterized, B-cell mediated damage is believed to be an important contributor. B-cells and autoantibodies may traverse the blood brain barrier promoting an inflammatory environment consisting of glia activation, neurodegeneration, and consequent averse behavioral outcomes. This review will evaluate the various suggested roles of B-cells and autoantibodies in NPSLE, as well as therapeutic modalities targeting these pathogenic mediators.

  4. Protein microarray applications: Autoantibody detection and posttranslational modification.

    Science.gov (United States)

    Atak, Apurva; Mukherjee, Shuvolina; Jain, Rekha; Gupta, Shabarni; Singh, Vedita Anand; Gahoi, Nikita; K P, Manubhai; Srivastava, Sanjeeva

    2016-10-01

    The discovery of DNA microarrays was a major milestone in genomics; however, it could not adequately predict the structure or dynamics of underlying protein entities, which are the ultimate effector molecules in a cell. Protein microarrays allow simultaneous study of thousands of proteins/peptides, and various advancements in array technologies have made this platform suitable for several diagnostic and functional studies. Antibody arrays enable researchers to quantify the abundance of target proteins in biological fluids and assess PTMs by using the antibodies. Protein microarrays have been used to assess protein-protein interactions, protein-ligand interactions, and autoantibody profiling in various disease conditions. Here, we summarize different microarray platforms with focus on its biological and clinical applications in autoantibody profiling and PTM studies. We also enumerate the potential of tissue microarrays to validate findings from protein arrays as well as other approaches, highlighting their significance in proteomics.

  5. Serum Autoantibodies as Biomarkers for Parkinsons Disease: Background and Utility

    Directory of Open Access Journals (Sweden)

    Cassandra A DeMarshall

    2015-10-01

    Full Text Available There are no definitive diagnostic tests for early detection, diagnosis and staging of Parkinson's disease (PD. Available methods have thus far failed to yield high accuracy, are expensive, and can be highly invasive to the patient. The use of serum biomarkers for the diagnosis of early-stage PD has the potential to provide an accurate, inexpensive, and non-invasive alternative to conventional tests. Recently, investigations into the role of the immune system in the development of PD and other diseases have led to the identification of potential PD-specific autoantibodies. This mini review focuses on the background and utility of these autoantibodies as diagnostic biomarkers of PD. Advantages of serum biomarkers as well as potential benefits of a blood-based diagnostic test to clinical medicine are discussed.

  6. Immunoregulation by naturally occurring and disease-associated autoantibodies

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Bendtzen, Klaus

    2012-01-01

    -receptors on antigen-presenting cells and thereby regulate T-cell activity. Knowledge of the influence of NAbs against cytokines on immune homeostasis is likely to have wide-ranging implications both in understanding pathogenesis and in treatment of many immunoinflammatory disorders, including a number of autoimmune......The role of naturally occurring autoantibodies (NAbs) in homeostasis and in disease manifestations is poorly understood. In the present chapter, we review how NAbs may interfere with the cytokine network and how NAbs, through formation of complement-activating immune complexes with soluble self......-antigens, may promote the uptake and presentation of self-molecules by antigen-presenting cells. Both naturally occurring and disease-associated autoantibodies against a variety of cytokines have been reported, including NAbs against interleukin (IL)-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony...

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

    Science.gov (United States)

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

    2016-09-14

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

  8. 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...

  9. Autoantibodies and Neuropsychiatric events at diagnosis of SLE

    Science.gov (United States)

    Hanly, J. G.; Urowitz, M. B.; Siannis, F.; Farewell, V.; Gordon, C.; Bae, S.C.; Isenberg, D.; Dooley, M.A.; Clarke, A.; Bernatsky, S.; Gladman, D.; Fortin, P.R.; Manzi, S.; Steinsson, K.; Bruce, I.; Ginzler, E.; Aranow, C.; Wallace, D.J.; Ramsey-Goldman, R.; Van Vollenhoven, R.; Sturfelt, G.; Nived, O.; Sanchez-Guerrero, J.; Alarcón, G.S.; Petri, M.; Khamashta, M.; Zoma, A.; Kalunian, K.; Douglas, J.; Qi, Qiufen; Merrill, J. T.

    2015-01-01

    Objective To examine the association between neuropsychiatric (NP) events with antiphospholipid antibodies (lupus anticoagulant, anticardiolipin), anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies in an international inception cohort. Methods NP events were identified using the ACR case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events was determined using decision rules of different stringency (model A and model B). Autoantibodies were measured without knowledge of NP events or their attribution. Results 412 patients (87.3% female; mean (± SD) age of 34.9 ± 13.5 years; mean disease duration 5.0 ± 4.2 months) were studied. There were 214 NP events in 133 (32.3%) patients. NP events attributed to SLE varied from 15% (model A) to 36% (model B). There was no association between autoantibodies and NP events from all causes. However the frequency of anti-ribosomal P antibodies in patients with NP events due to SLE (model A) was 4/24 (16.6%) compared to 3/109 (2.8%) for all other NP events and 24/279 (8.6%) with no NP events (P=0.07). Furthermore anti-ribosomal P antibodies in patients with central NP events attributed to SLE (model A) was 4/20 (20%) vs. 3/107 (2.8%) for other NP events and 24/279 (8.6%) with no NP events (P = 0.04). For diffuse NP events the antibody frequencies were 3/11 (27%) compared to 4/111 (3.6%) and 24/279 (8.6%) respectively (P=0.02). Conclusion NP events at onset of SLE were associated with anti-ribosomal P antibodies, suggesting a pathogenetic role for this autoantibody. There was no association with other autoantibodies. PMID:18311802

  10. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    OpenAIRE

    Lilla Mihályi; Mária Kiss; Attila Dobozy; Lajos Kemény; Sándor Husz

    2012-01-01

    The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin ...

  11. Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies.

    Science.gov (United States)

    Quaio, Caio R D C; Carvalho, Jozélio F; da Silva, Clovis A; Bueno, Cleonice; Brasil, Amanda S; Pereira, Alexandre C; Jorge, Alexander A L; Malaquias, Alexsandra C; Kim, Chong A; Bertola, Débora R

    2012-05-01

    The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

  12. 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.

  13. Neuromyelitis optica in a young child with positive serum autoantibody

    OpenAIRE

    Loma, Ingrid P.; Asato, Miya R.; Filipink, Robyn A.; Alper, Gulay

    2008-01-01

    Relapsing neuromyelitis optica is rare in children. The identification of highly specific serum autoantibody marker (neuromyelitis optica –immunoglobulin G) differentiates neuromyelitis optica from other demyelinating disorders particularly in clinically challenging cases. We present a child with multiple episodes of transverse myelitis and optic neuritis with positive neuromyelitis optica-immunoglobulin G titers consistent with a diagnosis of relapsing neuromyelitis optica. Serial titers of ...

  14. Adenine nucleotide concentrations in patients with erythrocyte autoantibodies.

    OpenAIRE

    Strong, V F; Sokol, R J; Rodgers, S A; Hewitt, S.

    1985-01-01

    Erythrocyte adenine nucleotide concentrations were measured in 154 patients with erythrocyte autoantibodies and 811 normal subjects using a luciferin-luciferase bioluminescent assay. The patients were initially divided into haemolysing and non-haemolysing groups. Red cell adenosine triphosphate (ATP) concentrations were significantly raised in the 96 patients with active haemolysis compared with the normal subjects and with the 58 patients in the non-haemolysing group. Although the patients c...

  15. 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.

  16. Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection.

    Science.gov (United States)

    Himoto, Takashi; Masaki, Tsutomu

    2012-01-01

    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.

  17. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    Directory of Open Access Journals (Sweden)

    Lilla Mihályi

    2012-01-01

    Full Text Available The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus, diamino diphenyl sulfone (dapsone therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

  18. 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.

  19. [Pathomechanisms of autoantibody production against the nervous system].

    Science.gov (United States)

    Arimura, Kimiyoshi

    2013-04-01

    In immune-mediated neurological disorders, the production of autoantibodies against the nervous system occurs mainly because of impaired immune tolerance. In myasthenia gravis (MG), the thymus shows pathologic alterations, particularly in anti-AChR antibody-positive patients. Further, resection of the thymus induces a clinical recovery. The MG thymus contains all the elements, including AChR antigens, AChR-specific T cells, and antigen-secreting B cells, that are required to initiate and sustain autoantibody production. Central tolerance, established by the repertoire selection of immature T lymphocytes in the thymus, is impaired in MG patients who are positive for anti-AChR antibodies. Recent evidence suggests that chronic inflammation elicited by viral infection is important for the production of AChR antibodies. Antibodies against ganglioside are crucial for the diagnosis of Guillain-Barre syndrome (GBS). Molecular mimicry between the lipooligosaccharides of Camplylobacter jejuni and gangliosides of the peripheral nerve causes the production of antibodies. However, less than 1 in 1000 patients infected with C. jejuni develop GBS. This fact suggests that some host factors might influence the production of antibodies. A recent hypothesis suggests that transient impairment of peripheral tolerance due to infection may play a crucial role in GBS pathogenesis. In summary, autoantibody production might correlate with the impairment of immune tolerance as well as with innate immunity.

  20. 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.

  1. 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.

  2. The Frequency Distribution of Celiac Autoantibodies in Alopecia Areata

    Science.gov (United States)

    Mokhtari, Fatemeh; Panjehpour, Tayebeh; Naeini, Farahnaz Fatemi; Hosseini, Sayed Mohsen; Nilforoushzadeh, Mohammad Ali; Matin, Marzieh

    2016-01-01

    Background: Alopecia areata (AA) is a noncicatricial (nonscarring) alopecia. The association between AA and celiac disease (CD) is debatable. Several studies declare the relationship between AA and CD as measurement of celiac autoantibodies (anti-gliadin IgA and anti-gliadin IgG), but a few studies consider anti-tissue transglutaminase IgA. The aim of this study was to evaluate the frequency distribution of celiac autoantibodies (all of them) in patients with AA compared with controls. Methods: This study is a case–control study. Thirty-five patients entered in each group. Anti-gliadin IgA, anti-gliadin IgG, and anti-tissue transglutaminase IgA were tested in all patients. Samples were examined in ELISA method with binding site's kits, and the result was reported as positive/negative. Finally, the frequency distribution of autoantibodies was examined. Results: The age average did not show a significant difference between two groups (P = 0.62). In addition, there was no significant difference between the two groups based on gender (P = 0.15). The prevalence of antibody in case and control groups was 2.85% and 0%, respectively. There was no significant difference between the two groups (P = 0.31). Conclusions: There may be a relationship between CD and AA, but the absence of statistical association between AA and CD does not mean that there is no relationship between gluten and AA in certain patients. Thus, we have shown here that the biological tests to search for CD do not bring information and proof enough, and it is why we recommend another approach to disclose gluten intolerance in AA patients. PMID:27833723

  3. 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.

  4. The influence of autoantibody status and characteristics on the course of rheumatoid arthritis

    NARCIS (Netherlands)

    Willemze, Annemieke

    2014-01-01

    The identification of ACPA has been a major breakthrough in the understanding of pathogenesis in RA. It has become clear that this unique autoantibody response identifies more homogenous subsets of patients with RA than those characterized by levels of other autoantibodies, and that differing diseas

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  6. Classification of idiopathic interstitial pneumonias using anti–myxovirus resistance-protein 1 autoantibody

    Science.gov (United States)

    Hamano, Yoshimasa; Kida, Hiroshi; Ihara, Shoichi; Murakami, Akihiro; Yanagawa, Masahiro; Ueda, Ken; Honda, Osamu; Tripathi, Lokesh P.; Arai, Toru; Hirose, Masaki; Hamasaki, Toshimitsu; Yano, Yukihiro; Kimura, Tetsuya; Kato, Yasuhiro; Takamatsu, Hyota; Otsuka, Tomoyuki; Minami, Toshiyuki; Hirata, Haruhiko; Inoue, Koji; Nagatomo, Izumi; Takeda, Yoshito; Mori, Masahide; Nishikawa, Hiroyoshi; Mizuguchi, Kenji; Kijima, Takashi; Kitaichi, Masanori; Tomiyama, Noriyuki; Inoue, Yoshikazu; Kumanogoh, Atsushi

    2017-01-01

    Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2–3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis. We identified disease-specific autoantibodies and enriched KEGG pathways unique to each disease, and demonstrated that IPF and INSIP are serologically distinct. Furthermore, we discovered a new INSIP-specific autoantibody, anti–myxovirus resistance-1 (MX1) autoantibody. Patients positive for anti-MX1 autoantibody constituted 17.5% of all cases of chronic fibrosing IIPs. Notably, patients rarely simultaneously carried the anti-MX1 autoantibody and the anti–aminoacyl-transfer RNA synthetase autoantibody, which is common in chronic fibrosing IIPs. Because MX1 is one of the most important interferon-inducible anti-viral genes, we have not only identified a new diagnostic autoantibody of INSIP but also obtained new insight into the pathology of INSIP, which may be associated with viral infection and autoimmunity. PMID:28230086

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

    DEFF Research Database (Denmark)

    Langkilde, Henrik; Voss, A; Heegaard, N

    2017-01-01

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

  8. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    Honglin Zhu; Hui Luo; Mei Yan; Xiaoxia Zuo; Quan-Zhen Li

    2015-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplas-mic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epi-topes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection.

  9. Autoantibodies against α1 adrenergic receptor related with cardiac remodeling in hypertensive patients by clinical observation

    Institute of Scientific and Technical Information of China (English)

    李正在

    2006-01-01

    Objective To investigate the effects of autoantibodies against a adrenergic receptor on cardiac remodeling in patients with hypertension. Methods Five hundred and fifty three patients with hypertension in our hospital were selected. The autoantibodies againstα1 adrenergic receptor in sera of donor were detected by ELISA, and the Results of echocardiography were recorded. By

  10. Prevalence of autoantibodies in a group of hereditary angioedema patients.

    Science.gov (United States)

    Dortas Junior, Sergio Duarte; Valle, Solange Oliveira Rodrigues; Levy, Soloni Afra Pires; Tortora, Rosangela P; Abe, Augusto Tiaqui; Pires, Gisele Viana; Papi, José Angelo de Souza; França, Alfeu Tavares

    2012-01-01

    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.

  11. Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Beppu, Minako; Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Kazami, Takahiro; Misawa, Sonoko; Shibuya, Kazumoto; Ishibashi, Masumi; Sogawa, Kazuyuki; Kado, Sayaka; Kodera, Yoshio; Nomura, Fumio; Kuwabara, Satoshi

    2015-10-15

    To identify the target molecules of chronic inflammatory demyelinating polyneuropathy (CIDP), we used proteomic-based approach in the extracted proteins from porcine cauda equina. Two of 31 CIDP patients had markedly elevated serum autoantibodies against vinculin, a cell adhesion protein. Both of the patients with anti-vinculin antibodies had similar clinical manifestation, which are compatible with those of "typical" CIDP. Immunocytochemistry showed that vinculin was stained at the myelin sheath of the sciatic nerves by serum samples. Our results suggest that vinculin is a possible immunological target molecule in a subpopulation of typical CIDP patients.

  12. 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

    Diabetes Genetics Consortium (T1DGC). These were tested for association with three islet autoantibodies—against autoantibodies to GAD (GADA), IA-2 (IA-2A), and zinc transporter 8 (ZnT8A)—and autoantibodies against thyroid peroxidase (TPOA) in autoimmune thyroid disease, gastric parietal cells (PCA......Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim...... of this study was to investigate whether susceptibility loci identified in genome-wide association studies (GWAS) of T1D were also associated with autoantibody positivity in individuals with diabetes. Fifty single nucleotide polymorphisms (SNPs) were genotyped in 6,556 multiethnic cases collected by the Type 1...

  13. Experimental erythrocyte autoantibodies. V. Induction and suppression of red blood cell autoantibodies in mice injected with rat bromelain-treated red blood cells.

    Science.gov (United States)

    Cox, K O; McAuliffe, A

    1983-10-01

    Mice injected with rat red blood cells (RBC), or rat bromelain-treated (brom) RBC, produce RBC autoantibodies and suppressor cells that specifically inhibit the autoimmune response without inhibiting the net production of antibodies against rat RBC. It has been investigated whether suppressor cells induced by injections of rat RBC are effective in preventing autoantibody production induced by rat brom RBC and vice versa. Autoantibodies were induced in C3H mice by weekly ip injections, each 0.2 ml, of a 6% suspension of rat RBC or rat brom RBC. Autoantibody production was assayed using Coombs' test. Suppressor cells were present in the spleens of mice positive in Coombs' tests and were shown by intravenous injections of 40 X 10(6) viable cells per mouse into untreated syngeneic mice 18 hr before the first injection of rat RBC or rat brom RBC. Autoantibodies eluted from mice positive in Coombs' tests after injections of rat RBC or brom RBC were absorbed by either type of rat RBC but not by RBC from sheep. This suggests that rat RBC and rat brom RBC display antigens that are similar, if not identical, to autoantigens on the mouse RBC. Spleen cells from mice injected with rat RBC suppressed autoantibodies induced by both rat RBC and rat brom RBC. In contrast, spleen cells from mice injected with rat brom RBC suppressed autoantibodies induced by rat brom RBC but not those induced by unmodified rat RBC. This differential suppression may be due to the removal from rat RBC, by bromelain, of a suppressor site and/or autoantigens of some specificities. Thus rat brom RBC may not induce the total range of specificities of autoantibodies, and of suppressor cells, induced by rat RBC.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    ), tissue transglutaminase, and 21-hydroxylase was tested using a linear mixed-model regression approach to simultaneously control for population structure and family relatedness. Four loci were associated with autoantibody positivity at genome-wide significance. Positivity for GADA was associated with 3q28......Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array...... and tested for association with seven disease-specific autoantibodies in a large cross-sectional cohort of 6,160 type 1 diabetes-affected siblings. The genetic association with positivity for GAD autoantibodies (GADAs), IA2 antigen (IA-2A), zinc transporter 8, thyroid peroxidase, gastric parietal cells (PCAs...

  15. 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.

  16. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Honglin Zhu

    2015-08-01

    Full Text Available Systemic lupus erythematosus (SLE is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins, cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

  17. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Zhu, Honglin; Luo, Hui; Yan, Mei; Zuo, Xiaoxia; Li, Quan-Zhen

    2015-08-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

  18. 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.

  19. 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.

  20. 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.

  1. Epileptic syndrome in systemic lupus erythematosus and neuronal autoantibody associations.

    Science.gov (United States)

    Kampylafka, E I; Alexopoulos, H; Fouka, P; Moutsopoulos, H M; Dalakas, M C; Tzioufas, A G

    2016-10-01

    We investigated systemic lupus erythematosus (SLE) patients with epilepsy, a major and organic neurological symptom. Our aim was to test patients for the autoimmune epilepsy-associated antibodies anti-GAD, anti-NMDAR, anti-AMPAR1/2, anti-GABABR and anti-VGKC. We tested sera from ten SLE patients with current or previous episodes of epileptic seizures. In addition, sera were tested for staining on primary hippocampal neurons. The patients' clinical and neuroimaging profile, disease activity and accumulated damage scores and therapeutic regimens administered were recorded, and correlations were evaluated. Patients were negative for all anti-neuronal autoantibodies tested, and showed no staining on primary hippocampal cells, which suggests the absence of autoantibodies against neuronal cell surface antigens. Epileptic seizures were all tonic-clonic, and all patients had high disease activity (mean SLE Damage Acticity Index score 19.3 ± 7.3). Six patients had minor or no brain magnetic resonance imaging findings, and three had major findings. 9/10 patients received immunosuppression for 5 ± 4 months, while anti-convulsive treatment was administered to all patients (4.2 ± 3 years). Our results suggest that the majority of SLE-related epileptic seizures cannot be attributed to the action of a single antibody against neuronal antigens. Studies with larger neuropsychiatric SLE populations and stricter inclusion criteria are necessary to verify these findings.

  2. Characterization Analysis of Human Anti-Ferritin Autoantibodies

    Directory of Open Access Journals (Sweden)

    Shusaku Higashi

    2014-03-01

    Full Text Available 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 IgA to bind to expressed recombinant human H and L chain homopolymers were also found. A portion of human serum proteins bound to zinc ions immobilized on beads were released upon the addition of canine liver ferritin, and the released protein was identified as IgM antibody. Additionally, the released proteins recognized peptide sequence (DPHLCDF commonly found in amino acid sequences of mammalian ferritin H and L subunits. These results suggest that human serum contains anti-ferritin autoantibodies (IgG, IgM and IgA which bind zinc ions and preferentially bind ferritin over both the H and L subunits, and that a portion of, but not all, the IgM antibodies bound to ferritin with higher affinity than to zinc ions and may recognize the common sequence found in mammalian ferritin H and L subunits.

  3. 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.

  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.

  5. 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

  6. Elevated Plasma P-Selectin Autoantibodies in Primary Sjögren Syndrome Patients with Thrombocytopenia.

    Science.gov (United States)

    Hu, Ya-Hui; Zhou, Peng-Fei; Long, Guang-Feng; Tian, Xin; Guo, Yu-Fan; Pang, Ai-Ming; Di, Ran; Shen, Yan-Na; Liu, Yun-De; Cui, Yu-Jie

    2015-11-28

    BACKGROUND Primary Sjögren's syndrome (pSS) is one of the most common chronic systemic autoimmune diseases, and thrombocytopenia is one of the hematological manifestations of pSS. When platelet and endothelial cells are activated, P-selectin is expressed on the cell surface. This study aimed to investigate the role of P-selectin autoantibodies in the pathogenesis of thrombocytopenia in pSS. MATERIAL AND METHODS P-selectin autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 38 pSS patients without thrombocytopenia and 32 pSS patients with thrombocytopenia, 32 idiopathic thrombocytopenic purpura (ITP) patients, and 35 healthy controls. RESULTS The plasma P-selectin autoantibodies (A490) in ITP patients and pSS patients with/without thrombocytopenia were significantly higher than those in healthy controls, but there were no significant differences between ITP patients and pSS patients with thrombocytopenia. The positive rate of P-selectin autoantibodies in pSS patients with thrombocytopenia was significantly higher than that in ITP patients. The platelet count was lower in P-selectin autoantibodies-positive patients, while among pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients than in P-selectin autoantibodies-negative patients. In ITP patients and pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients. CONCLUSIONS Elevated plasma P-selectin autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS patients.

  7. The correlation between peripartum cardiomyopathy and autoantibodies against cardiovascular receptors.

    Directory of Open Access Journals (Sweden)

    Jiamei Liu

    Full Text Available BACKGROUND: Peripartum cardiomyopathy (PPCM is characterized by left ventricular systolic dysfunction and heart failure. However, its pathogenesis is not clear. Our preliminary study revealed that autoantibodies against β1-adrenergic receptors (β1R-AABs and M2-muscarinic receptors (M2R-AABs participated in heart failure regardless of primary heart disease. Whether β1R-AABs and M2R-AABs participate in the pathogenesis of PPCM is still unknown. METHODS: Totally 37 diagnosed PPCM patients and 36 normal pregnant women were enrolled in this study. Clinical assessment and 2-dimensional echocardiographic studies as well as the measurement of β1R-AABs or M2R-AABs by enzyme linked immunosorbent assay (ELISA were performed. RESULTS: The positive rates for β1R-AABs and M2R-AABs were 59.5% (22/37 and 45.9% (17/37 in PPCM patients, and 19.4% (7/36 (P<0.001 and 16.67% (6/36 (P<0.001 in normal pregnant women, respectively. Both β1R-AABs and M2R-AABs had a positive correlation with serum expression level of NT-proBNP, left ventricular dimension and NYHA FC (rs: 0.496-0.892, P<0.01. In addition, a negative correlation between the activity of β1R-AABs and M2R-AABs and LVEF, LVFS was observed (rs: -0.488-0.568, P<0.01. Moreover, autoantibodies against cardiovascular receptors increased the risk of the onset of PPCM (OR = 18.786, 95% confidence interval 1.926-183.262, P = 0.012. CONCLUSIONS: The β1R-AABs and M2R-AABs reveal a significant elevation and are correlated with the increased left ventricular dimension and worse cardiac contraction function. The autoantibodies of cardiovascular receptors are independent risk factors for the onset of PPCM.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  9. Complete atrioventricular block in adult Sjögren's syndrome with anti-Ro autoantibody.

    Science.gov (United States)

    Sung, Myung Jun; Park, Sung-Hoon; Kim, Seong-Kyu; Lee, Young-Soo; Park, Chul-Yeon; Choe, Jung-Yoon

    2011-06-01

    Anti-Ro autoantibody is associated with Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and neonatal lupus syndrome (i.e., congenital complete heart block in newborns). Generally, the adult atrioventricular (AV) node is believed to be relatively resistant to the scarring effects of anti-Ro/anti-La autoantibodies. However, there have been some reports of adult complete AV block in SS and SLE patients. Here, we report a case of complete heart block in primary SS with anti-Ro autoantibodies, with no other risk factor for the development of heart block, and review their etiological association.

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

    DEFF Research Database (Denmark)

    Landegren, Nils; Pourmousa Lindberg, Mina; Skov, Jakob

    2016-01-01

    Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients...... with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies...

  11. 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.

  12. 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...

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

    Science.gov (United States)

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

    1979-10-01

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

  14. 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.

  15. A study of type-1 diabetes associated autoantibodies in schizophrenia.

    Science.gov (United States)

    Hallford, Philomena; Clair, David St; Halley, Lorna; Mustard, Colette; Wei, Jun

    2016-10-01

    Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.

  16. CYP2E1 autoantibodies in liver diseases

    Science.gov (United States)

    Sutti, Salvatore; Rigamonti, Cristina; Vidali, Matteo; Albano, Emanuele

    2014-01-01

    Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression. PMID:25462068

  17. [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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-03-01

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

  19. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes

    DEFF Research Database (Denmark)

    Wandall, Hans H; Blixt, Ola; Tarp, Mads A;

    2010-01-01

    -glycopeptide microarray was developed that detected IgG antibodies to aberrant O-glycopeptide epitopes in patients vaccinated with a keyhole limpet hemocyanin-conjugated truncated MUC1 peptide. We detected cancer-associated IgG autoantibodies in sera from breast, ovarian, and prostate cancer patients against different......Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we...... evaluated whether autoantibodies generated to aberrant O-glycoforms of MUC1 might serve as sensitive diagnostic biomarkers for cancer. Using an antibody-based glycoprofiling ELISA assay, we documented that aberrant truncated glycoforms were not detected in sera of cancer patients. An O...

  20. 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.

  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;

    2014-01-01

    been exposed to environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and PFCs were measured in 38 children in the Faroe Islands who were exposed to widely different levels of these chemicals due to their seafood-based diet. Concentrations of IgM and IgG autoantibodies specific......Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds (PFCs) are ubiquitous and persistent environmental chemicals with known or suspected toxic effects on the nervous system and the immune system. Animal studies have shown that tissue damage can elicit production...... of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibodies specific for neural and non-neural antigens could be detected in children at age 7 years who have...

  2. 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...

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

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2012-01-01

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

  4. 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.

  5. Autoantibodies against serotoninergic 5-HT(4) receptor in patients with heart failure.

    Science.gov (United States)

    Breidert, M; Wördehoff, S; Hansen, A; Eftekhari, P

    2012-01-01

    Serotoninergic 5-HT(4) receptors have been detected in several tissues including the heart. An autoimmune mechanism may underline the pathogenesis of heart failure. The aim of this work was to look for autoantibodies to the 5-HT(4) receptor in patients with heart failure. We looked for the presence of autoantibodies against 5-HT(4) receptor as well as angiotensin II type (AT1), β(1)-adrenoceptor, and muscarinic M2 receptors in the sera of 176 patients with heart failure (female: n=96, male: n=80) and in 108 controls (female: n=69; male: n=39). The prevalence of 5-HT(4) receptor autoantibodies was 18.8% (n=33) in the group of patients with heart failure and 4.6% (n=5) in the control group (preceptor M2 4.2 (n=5). Female patients with diabetes and heart failure had a positive trend (p=0.07) to the presence of 5-HT(4) receptor autoantibodies. In the group of female heart failure patients we found a significant correlation with the presence of coronary heart disease (p=0.05). The clinical relevance of 5-HT(4) receptor autoantibodies has to be further studied. The prevalence of 5-HT(4) receptor autoantibodies was highly significant in patients with chronic heart failure. It was also a significant correlation between these autoantibodies and the female subgroup with coronary heart disease. It is conceivable that the increased prevalence of autoantibodies against the 5-HT(4) receptor in patients with heart failure is more than just an epiphenomenon.

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

    Directory of Open Access Journals (Sweden)

    Andrzej Chruscinski

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

  7. 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.

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

    Science.gov (United States)

    Lampasona, Vito; Passerini, Laura; Barzaghi, Federica; Lombardoni, Carlo; Bazzigaluppi, Elena; Brigatti, Cristina; Bacchetta, Rosa; Bosi, Emanuele

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Neil M. Gude BSc, MSc, PhD

    2013-10-01

    Full Text Available 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.

  10. 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.

  11. A panel of autoantibodies as potential early diagnostic serum biomarkers in patients with cervical cancer.

    Science.gov (United States)

    Huangfu, Mingmei; Xu, Shuang; Li, Siyao; Sun, Baosheng; Lee, Kuang-Hui; Liu, Linlin; Sun, Shilong

    2016-07-01

    The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P = 0.063; P = 0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P cervical cancer group than in the healthy control group (P = 0.010; P = 0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8 % and a specificity of 90 %, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens.

  12. Purification of human immunoglobulin G autoantibodies to tumor necrosis factor using affinity chromatography and magnetic separation.

    Science.gov (United States)

    Sennikov, S V; Golikova, E A; Kireev, F D; Lopatnikova, J A

    2013-04-30

    Autoantibodies to cytokines are important biological effector molecules that can regulate cytokine activities. The aim of the study was to develop a protocol to purify autoantibodies to tumor necrosis factor from human serum, for use as a calibration material to determine the absolute content of autoantibodies to tumor necrosis factor by enzyme-linked immunosorbent assay. The proposed protocol includes a set of affinity chromatography methods, namely, Bio-Gel P6DG sorbent to remove albumin from serum, Protein G Sepharose 4 Fast Flow to obtain a total immunoglobulin G fraction of serum immunoglobulins, and Affi-Gel 15 to obtain specifically antibodies to tumor necrosis factor. The addition of a magnetic separation procedure to the protocol eliminated contaminant tumor necrosis factor from the fraction of autoantibodies to tumor necrosis factor. The protocol generated a pure fraction of autoantibodies to tumor necrosis factor, and enabled us to determine the absolute concentrations of different subclasses of immunoglobulin G autoantibodies to tumor necrosis factor in apparently healthy donors.

  13. 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

  14. [Interferon alpha antibodies show no cross reactions with typical autoantibodies].

    Science.gov (United States)

    Görg, S; Klouche, M; Wilhelm, D; Kirchner, H

    1993-04-01

    Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.

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

    Directory of Open Access Journals (Sweden)

    Azin Alavi

    2012-01-01

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

  16. SLAP deficiency decreases dsDNA autoantibody production.

    Science.gov (United States)

    Peterson, Lisa K; Pennington, Luke F; Shaw, Laura A; Brown, Meredith; Treacy, Eric C; Friend, Samantha F; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V; Dragone, Leonard L

    2014-02-01

    Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection.

  17. 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.

  18. Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis*

    Science.gov (United States)

    Vasilev, Vasil V.; Noe, Remi; Dragon-Durey, Marie-Agnes; Chauvet, Sophie; Lazarov, Valentin J.; Deliyska, Boriana P.; Fremeaux-Bacchi, Veronique; Dimitrov, Jordan D.; Roumenina, Lubka T.

    2015-01-01

    Lupus nephritis (LN) is a complication of the autoimmune disease systemic lupus erythematosus. Because the complement system plays a critical role in orchestrating inflammatory and immune responses as well as in the clearance of immune complexes, autoreactivity to complement components may have considerable pathological consequences. Autoantibodies against the central complement component C3 have been reported in systemic lupus erythematosus, but their molecular mechanism and functional relevance are not well understood. The objective of this study was to evaluate the frequency and the functional properties of the anti-C3 autoantibodies. Anti-C3 autoantibodies were measured in plasma of 39 LN patients, and identification of their epitopes on the C3 molecule was performed. By using surface plasmon resonance, we analyzed the influence of patient-derived IgG antibodies on the interaction of C3b with Factor B, Factor H, and complement receptor 1. The capacity of these antibodies to dysregulate the C3 convertase on the surface of endothelial cell was measured by flow cytometry. Here we report that the frequency of anti-C3 autoantibodies in LN is ∼30%. They inhibited interactions of the negative complement regulators Factor H and complement receptor 1 with C3b. An enhanced C3 deposition was also observed on human endothelial cells in the presence of C3 autoantibodies. In addition, anti-C3 autoantibody levels correlated with disease activity. In conclusion, the anti-C3 autoantibodies in LN may contribute to the autoimmune pathology by their capacity to overactivate the complement system. PMID:26245903

  19. Synaptic and Neuronal Autoantibody-Associated Psychiatric Syndromes: Controversies and Hypotheses

    Science.gov (United States)

    Al-Diwani, Adam; Pollak, Thomas A.; Langford, Alexander E.; Lennox, Belinda R.

    2017-01-01

    Autoimmune encephalitis (AE) mediated by antibodies against synaptic and neuronal surface targets frequently presents with a psychiatric syndrome. In these patients, removal of autoantibodies treats the disease and outcomes are closely linked to early intervention. The discovery of these autoantibodies in isolated psychiatric syndromes has raised the possibility that these patients may derive similar benefits from immunotherapy, a potentially transformational approach to the treatment of mental illness. Although open-label case series suggest impressive therapeutic outcomes, the pathological relevance of these autoantibodies outside of canonical presentations is debated. The advent of diagnostic criteria for AE attempts to facilitate its prompt identification but risks prematurely neglecting the potential scientific and clinical significance of isolated syndromes that do not satisfy these criteria. Here, we propose using a syndrome-level taxonomy that has occasional, but not necessary, overlap with AE: synaptic and neuronal autoantibody-associated psychiatric syndromes or “SNAps”. This will prevent confusion with AE and act heuristically to promote active investigation into this rare example of psychopathology defined on a molecular level. We suggest that this concept would have application in other autoantibody-associated syndromes including seizure, cognitive, and movement disorders, in which similar issues arise. We review putative direct and indirect mechanisms and outline experimentally testable hypotheses that would help to determine prospectively in whom autoantibody detection is relevant, and as important, in whom it is not. We summarize a pragmatic approach to autoantibody testing and management in severe mental illness in order to promptly diagnose AE and advocate a research-orientated experimental medicine paradigm for SNAps, where there is greater equipoise. We conclude that SNAps remains a nascent area of clinical neuroscience with great potential

  20. Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: A pilot study

    Institute of Scientific and Technical Information of China (English)

    Nikolaos K. Gatselis; Sarah P. Georgiadou; Nikolaos Tassopoulos; Kalliopi Zachou; Christos Liaskos; Angelos Hatzakis; Georgios N. Dalekos

    2005-01-01

    AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients.METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustainedresponders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three timepoints (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs.RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy.CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- α may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.

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

    Directory of Open Access Journals (Sweden)

    Katy Milne

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

  2. Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans.

    Science.gov (United States)

    Toplak, N; Avcin, T

    2009-11-01

    Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vaccination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination-induced autoantibodies in apparently healthy subjects including studies in animals and humans.

  3. Voltage-gated potassium channels autoantibodies in a child with rasmussen encephalitis.

    Science.gov (United States)

    Spitz, Marie-Aude; Dubois-Teklali, Fanny; Vercueil, Laurent; Sabourdy, Cécile; Nugues, Frédérique; Vincent, Angela; Oliver, Viviana; Bulteau, Christine

    2014-10-01

    Rasmussen encephalitis (RE) is a severe epileptic and inflammatory encephalopathy of unknown etiology, responsible for focal neurological signs and cognitive decline. The current leading hypothesis suggests a sequence of immune reactions induced by an indeterminate factor. This sequence is thought to be responsible for the production of autoantibody-mediated central nervous system degeneration. However, these autoantibodies are not specific to the disease and not all patients present with them. We report the case of a 4-year-old girl suffering from RE displaying some atypical features such as fast evolution and seizures of left parietal onset refractory to several antiepileptics, intravenous immunoglobulins, and corticosteroids. Serum autoantibodies directed against voltage-gated potassium channels (VGKC) were evidenced at 739 pM, a finding never previously reported in children. This screening was performed because of an increased signal in the temporolimbic areas on brain magnetic resonance imaging, which was similar to what is observed during limbic encephalitis. The patient experienced epilepsia partialis continua with progressive right hemiplegia and aphasia. She underwent left hemispherotomy at the age of 5.5 years after which she became seizure free with great cognitive improvement. First described in adults, VGKC autoantibodies have been recently described in children with various neurological manifestations. The implication of VGKC autoantibodies in RE is a new observation and opens up new physiopathological and therapeutic avenues of investigation.

  4. Relevance of anti-C1q autoantibodies to lupus nephritis.

    Science.gov (United States)

    Tsirogianni, Alexandra; Pipi, Elena; Soufleros, Kostantinos

    2009-09-01

    The first component of the classical pathway of the complement system (C1q) is considered to have a crucial role in the clearance of immune complexes (ICs) as well as in the removal of waste material originating from apoptotic cells. A prolonged exposure of C1q epitopes to the immune system could eventually lead to an autoimmune response against itself. Although autoantibodies against C1q are found in several diseases, their clinical interest originates from their strong association to active lupus nephritis (LN). Several studies indicate that anti-C1q autoantibodies could serve as a reliable serologic marker in the assessment of LN activity compared to other immunological tests. Additionally, it was suggested that anti-C1q autoantibodies could play a role in LN pathogenesis. Their potential pathogenic actions likely depend on genetic background, titers, Ig classes and subclasses, and specific epitopes of anti-C1q autoantibodies as well as C1q availability and allocation. It is still unclear which different types of anti-C1q autoantibodies dominate in each case and if their upregulation is pathogenic, an epiphenomenon of aberrant tissue damage, or compensatory to an uncontrolled immune response.

  5. Utility of autoantibodies as biomarkers for diagnosis and staging of neurodegenerative diseases.

    Science.gov (United States)

    DeMarshall, Cassandra; Sarkar, Abhirup; Nagele, Eric P; Goldwaser, Eric; Godsey, George; Acharya, Nimish K; Nagele, Robert G

    2015-01-01

    Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. This chapter first presents well-known examples of autoimmune diseases that emphasize a direct causal role for autoantibodies and then discusses the veritable explosion of evidence now supporting their involvement in a wide variety of other diseases, including cancers and several types of neurological and neurodegenerative diseases. Lastly, translational strategies that take advantage of the "cause and/or effect" role of autoantibodies and recent technological advancements in their detection to exploit autoantibodies as sensitive and specific biomarkers useful for the detection and diagnosis of disease are outlined. Their use in the diagnosis and staging of Alzheimer's and Parkinson's diseases is presented, and future applications in clinical medicine and basic science are highlighted.

  6. Detection of autoantibodies in a point-of-care rheumatology setting.

    Science.gov (United States)

    Konstantinov, Konstantin N; Tzamaloukas, Antonios; Rubin, Robert L

    2013-08-01

    Autoimmune rheumatic diseases are common and confront society with serious medical, social, and financial burdens imposed by their debilitating nature. Many autoimmune diseases are associated with a particular set of autoantibodies, which have emerged as highly useful to define and classify disease, predict flares, or monitor efficacy of therapy. However, current practice for monitoring autoantibodies is protracted, labor-intensive, and expensive. This review provides an overview on the value of point-of-care (POC) biosensor technology in the diagnosis and management of patients with autoimmune rheumatic diseases. Real-time measurement of autoantibodies will clearly benefit the rheumatology practice in emergency and urgent care settings, where definitive diagnosis is essential for initiation of correct critical care therapy. Immediate serological information in clinic will provide considerable value for long-term patient care and an opportunity for an instant, result-deduced therapeutic action, avoiding delays and improving compliance, especially in field-based and remote areas. We describe the particular autoantibodies that are useful disease and activity markers and would, therefore, be attractive to POC applications. Already existing biosensors and platforms that show promise for autoantibody testing are summarized and comparatively evaluated. As POC assessment is gaining momentum in several areas of patient care, we propose that rheumatology is poised to benefit from this innovative and affordable technology.

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

    Science.gov (United States)

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

    2015-01-01

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

  8. 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.

  9. The Clinical Features of Myositis-Associated Autoantibodies: a Review.

    Science.gov (United States)

    Gunawardena, Harsha

    2017-02-01

    The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases traditionally defined by clinical manifestations including skeletal muscle weakness, skin rashes, elevated skeletal muscle enzymes, and neurophysiological and/or histological evidence of muscle inflammation. Patients with myositis overlap can develop other features including parenchymal lung disease, inflammatory arthritis, gastrointestinal manifestations and marked constitutional symptoms. Although patients may be diagnosed as having polymyositis (PM) or dermatomyositis (DM) under the IIM spectrum, it is quite clear that disease course between subgroups of patients is different. For example, interstitial lung disease may predominate in some, whereas cutaneous complications, cancer risk, or severe refractory myopathy may be a significant feature in others. Therefore, tools that facilitate diagnosis and indicate which patients require more detailed investigation for disease complications are invaluable in clinical practice. The expanding field of autoantibodies (autoAbs) associated with connective tissue disease (CTD)-myositis overlap has generated considerable interest over the last few years. Using an immunological diagnostic approach, this group of heterogeneous conditions can be separated into a number of distinct clinical phenotypes. Rather than diagnose a patient as simply having PM, DM or overlap CTD, we can define syndromes to differentiate disease subsets that emphasise clinical outcomes and guide management. There are now over 15 CTD-myositis overlap autoAbs found in patients with a range of clinical manifestations including interstitial pneumonia, cutaneous disease, cancer-associated myositis and autoimmune-mediated necrotising myopathy. This review describes their diagnostic utility, potential role in disease monitoring and response to treatment. In the future, routine use of these autoAb will allow a stratified approach to managing this complex set of conditions.

  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. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Ola H Negm

    Full Text Available 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.

  12. Nucleosomes and C1q bound to glomerular endothelial cells serve as targets for autoantibodies and determine complement activation

    NARCIS (Netherlands)

    O'Flynn, J.; Flierman, R.; Pol, P. van der; Meulemans-Rops, L.W.M.; Satchell, S.C.; Mathieson, P.W.; Kooten, C. van; Vlag, J. van der; Berden, J.H.M.; Daha, M.R.

    2011-01-01

    Various studies indicate a role for both anti-nucleosome and anti-C1q autoantibodies in glomerulonephritis in patients with systemic lupus erythematosus. However, a causal relationship between these autoantibodies and the development of lupus nephritis has not been fully established. Since injury of

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

    Science.gov (United States)

    Suppiah, Aravind; Greenman, John

    2013-08-07

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

  14. An increased frequency of autoantibody-inducing CD4+ T cells in pre-diseased lupus-prone mice.

    Science.gov (United States)

    Busser, Brian W; Cancro, Michael P; Laufer, Terri M

    2004-07-01

    Pathogenic autoantibody production in murine models of lupus is dependent on autoreactive CD4+ helper T cells. However, the mechanisms which permit the selection and maintenance of this autoantibody-inducing CD4+ T-cell repertoire are currently unknown. We hypothesized that the peripheral CD4+ T-cell repertoire of lupus-prone mice was enriched with autoantibody-inducing specificities. To test this, we utilized the splenic focus assay to determine if pre-diseased lupus-prone (NZB x NZW)F(1) mice have an elevated frequency of autoreactive CD4+ T lymphocytes capable of supporting autoantibody production. The splenic focus limiting dilution assay permits anti-nuclear antibodies to be generated from contact-dependent T-B interactions in vitro. We show that young, pre-diseased lupus-prone mice have an elevated frequency of autoantibody-inducing CD4+ T cells. Interestingly, these autoantibody-inducing CD4+ T-cell responses are also present in the thymus. Therefore, an elevated frequency of autoantibody-inducing CD4+ T cells predisposes lupus-prone mice to the development of autoantibodies.

  15. 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.

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  18. 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

    2016-08-03

    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.

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

    Directory of Open Access Journals (Sweden)

    Eric Nagele

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    The objective of this study was to determine whether IgG and IgM autoantibodies to folate receptor alpha (FRalpha) in pregnant women are associated with an increased risk of oral cleft-affected offspring. A case-control study nested in the prospective Danish National Birth Cohort (100,418 pregnan......The objective of this study was to determine whether IgG and IgM autoantibodies to folate receptor alpha (FRalpha) in pregnant women are associated with an increased risk of oral cleft-affected offspring. A case-control study nested in the prospective Danish National Birth Cohort (100.......04). Blocking of folate binding to FR was similar among cases and controls (p = 0.54). The results did not change when stratifying into the cleft subgroups, nor when only isolated oral cleft cases were considered. In conclusion, high maternal autoantibody levels and blocking of folate binding to FRalpha...

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

    Directory of Open Access Journals (Sweden)

    Ryabenko D. V.

    2010-09-01

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

  2. PATHOGENETIC ROLE OF ABZYME-TYPE AUTOANTIBODIES IN THE ORGAN-SPECIFIC AUTOIMMUNE PATHOLOGY

    Directory of Open Access Journals (Sweden)

    L. N. Luchverchyk

    2011-01-01

    Full Text Available Abstract. The work deals with quantitative methods developed for estimation of nuclease and proteolytic activities  of  autoantibodies.  By  means  of  these  techniques,  appropriate  catalytic  activities  of  abzyme-type antibodies were studied in patients with diabetes mellitus type 1, and in subjects with autoimmune thyroiditis. Oppositely directed changes of the mentioned catalytic activities have been found for autoantibodies of different specificity.  Autoantibodies  occurring  in  autoimmune  thyroiditis  showed  an  increase  of  both  nuclease  and proteolytic activities. Meanwhile, the autoantibodies in diabetes mellitus had increased nuclease activity, along with decreased proteolytic activity. These findings are suggestive for existence of two pathogenetic mechanisms in organ-specific autoimmune pathology that are associated either with direct involvement of Fab fragments of auto-antibodies in autoimmune destruction, or with complement-dependent lysis mediated by Fc-fragments and  cytotoxic  destruction  of  target  cells  by  cytotoxic T-lymphocytes.  The  unique  site-specific  catalytic autoantibodies  were  established  to  exert  a  selective destructive effect upon target cells, thus making a major contribution to the antibody-dependent mechanisms of cytotoxicity in autoimmune diseases. (Med. Immunol., 2011, vol. 13, N 2-3, pp 145-150

  3. 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.

  4. [Measurement of human thyroid peroxidase autoantibodies by enzyme immunoassay using recombinant human TPO].

    Science.gov (United States)

    Inoue, T; Ishiguro, R; Takenouchi, H; Umeki, K; Matsumoto, K; Yagihashi, S; Kato, H; Kotani, T; Ohtaki, S

    1994-03-01

    An EIA for measuring anti-TPO autoantibodies (rhTPO-EIA) was developed using recombinant human TPO expressed in CHO cells and was compared with MC-HA generally used in laboratory routine work. rhTPO-EIA showed a satisfactory reproducibility in the intra-assay test and did not have an accidental error of lots. Almost equal number of healthy females and males were measured for their IgG binding to TPO to define a normal range of anti-TPO autoantibodies. After setting 20 IU/ml as an upper limit of normal range, sera from patient with thyroid disorders were measured for their anti-TPO autoantibodies. Chronic thyroiditis and Graves' disease were highly positive, while adenoma, thyroid cancer, SLE, and RA were low in their positivity. The positive rate of anti-TPO autoantibodies was compatible to those of previous reports in each disorder. Seventy-two sera from patients with chronic thyroiditis or Graves' disease were measured for their autoantibodies by both rhTPO-EIA and MC-HA and the results were compared between both methods. A correlation coefficient was 0.486. Following absorption with thyroglobulin, sera were measured again and as the results, the correlation coefficient increased to 0.723. Therefore, MC-HA was thought to be influenced in the presence of anti-thyroglobulin autoantibodies. Since rhTPO-EIA is excellent in quality and not affected by anti-thyroglobulin antibodies, it is useful and applicable to clinical diagnosis and observation of thyroid disorders.

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

    Science.gov (United States)

    Melikyan, G; Abdelrahman, M H; D'Suoza, A; 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 disease manifestations. The two patients were treated successfully with IV steroids and cyclophosphamide.

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

    Directory of Open Access Journals (Sweden)

    N. V. Piven

    2011-01-01

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

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

    Science.gov (United States)

    Beck, Katherine; Lally, John; Shergill, Sukhwinder S; Bloomfield, Michael A P; MacCabe, James H; Gaughran, Fiona; Howes, Oliver D

    2015-02-01

    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 account for a large proportion of treatment-refractory psychosis.

  8. [How can we diagnose and better understand inflammatory myopathies? The usefulness of auto-antibodies].

    Science.gov (United States)

    Sibilia, Jean; Chatelus, Emmanuel; Meyer, Alain; Gottenberg, Jacques-Eric; Sordet, Christelle; Goetz, Joëlle

    2010-10-01

    The inflammatory myopathies are a group of quite proteiform, systemic auto-immune diseases which include polymyositis, dermatomyositis and inclusion body myopathies. To facilitate the diagnosis, classification criteria (Bohan and Peter, 1975) have been proposed, based essentially on clinical criteria. In addition, over the past fifteen years, auto-antibodies characterizing certain forms of inflammatory myopathy have been identified. One distinguishes schematically: auto-antibodies specific for myositis and auto-antibodies sometimes associated with myositis. Concerning the myositis specific auto-antibodies (MSA), schematically there are a dozen specificities which are classed according to the cellular distribution of the auto-antigen. The most characteristic are certainly the auto-antibodies directed against cytoplasmic antigens: the anti-tRNA synthetases (anti-Jo-1 (PL-1), anti-PL-7, PL-12, EJ, OJ, JS, KS, ZO, YRS), anti-SRP (signal recognition particle), anti-Mas and anti-KJ, anti-Fer (eEF1), anti-Wa and anti-CADM p140. Other auto-antibodies are directed against nuclear auto-antigens: the anti-Mi-2, anti-PMS (PMS1, PMS2) and related antibodies (MLH1, DNA PKcs…), anti-56 kDa, anti-MJ (NXP-2), anti-SAE and anti-p155/p140 (TIF-1γ). Concerning the auto-antibodies sometimes associated with myositis (myositis associated auto-antibodies or MAA), they can also be observed in other auto-immune diseases. These auto-antibodies are directed against nuclear or nucleolar auto-antigens: the anti-PM-Scl, anti-Ku, anti-RNP (U1 RNP and U2 RNP, U4/U6 RNP and U5 RNP), anti-Ro 52 kDa and more rarely, anti-Ro 60 kDa and anti-La. The auto-antibodies related to myositis are biological tools which are of interest in two main ways. They have allowed us to sort out the nosology of these inflammatory myopathies, in particular by defining anti-tRNA synthetase syndrome. It now remains to determine how they might be employed to complement the classical clinico-biological diagnostic criteria

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

    Directory of Open Access Journals (Sweden)

    Jimena Sanz-Bueno

    2014-01-01

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

  10. 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.

  11. Genetics, autoantibodies and clinical features in understanding and predecting rheumatoid arthritis

    NARCIS (Netherlands)

    Helm-van Mil, Anna Helena Maria van der

    2006-01-01

    This thesis investigated the association between several genetic factors and autoantibodies and the development of undifferentiated arthritis (UA) and rheumatoid arthritits (RA). Second, this thesis described a prediction model that estimates the chance to progress from UA to RA. The most important

  12. 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

    2015-01-01

    Key Clinical Message 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

  13. IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis

    NARCIS (Netherlands)

    Horvath, Barbara; Niedermeier, Andrea; Podstawa, Eva; Mueller, Ralf; Hunzelmann, Nicolas; Karpati, Sarolta; Hertl, Michael

    2010-01-01

    Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120-kDa protein w

  14. 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.

  15. An enzyme-linked immunosorbent assay for autoantibodies against the nuclear protein Scl-70

    DEFF Research Database (Denmark)

    Geisler, C; Høier-Madsen, M

    1985-01-01

    This paper describes the development of an enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of autoantibodies against the nuclear protein Scl-70. The isolation of Scl-70 from rat livers and the conditions for the ELISA are described. Compared with the already established...

  16. 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...

  17. A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells

    Science.gov (United States)

    Noble, Philip W.; Young, Melissa R.; Bernatsky, Sasha; Weisbart, Richard H.; Hansen, James E.

    2014-01-01

    Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A subset of lupus autoantibodies is associated with nucleolytic activity, and some of these antibodies are capable of nuclear penetration. We hypothesized that such antibodies might have potential as therapeutic agents targeted towards DNA repair-deficient malignancies. We identified the lupus autoantibody 5C6 as a cell-penetrating nucleolytic antibody and found that 5C6 has a differential effect on a matched pair of BRCA2-proficient and deficient DLD1 colon cancer cells. 5C6 selectively induced γH2AX in, and suppressed the growth of, the BRCA2-deficient cells. These findings demonstrate the potential utility of 5C6 in targeted therapy for DNA repair-deficient malignancies and strengthen the rationale for studies of additional lupus autoantibodies in order to identify the best candidates for development as therapeutic agents. In addition, the toxic effect of 5C6 on BRCA2-deficient cells provides further support for the hypothesis that some lupus autoantibodies contribute to the lower risk of specific cancers associated with systemic lupus erythematosus. PMID:25091037

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

    NARCIS (Netherlands)

    Swets, BP; Brouwer, DAJ; Tervaert, JWC

    2001-01-01

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

  19. 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...

  20. Usefulness of antineutrophil cytoplasmic autoantibodies in diagnosing and managing systemic vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2016-01-01

    Purpose of reviewAntineutrophil cytoplasmic autoantibodies (ANCAs) are considered important diagnostic tests in the work-up of patients suspected of vasculitis. Here we discuss new developments in the methodology of testing, the pitfalls in using these tests as diagnostic tools, and the value of ser

  1. 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.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  3. Natural autoantibodies in Bos taurus calves during the first twelve weeks of life

    NARCIS (Netherlands)

    Mayasari, N.; Knegsel, van A.T.M.; Vries Reilingh, de G.; Kemp, B.; Parmentier, H.K.

    2016-01-01

    Natural autoantibodies (NAAb) have a role in maintaining physiological homeostasis and prevention of infections, and have been found in mammalian species tested so far. Albeit NAAb levels rise with age, little is known about the origin, function, regulation and initiation of NAAb in young animals

  4. Diagnosis of Parkinson's disease based on disease-specific autoantibody profiles in human sera.

    Directory of Open Access Journals (Sweden)

    Min Han

    Full Text Available Parkinson's disease (PD, hallmarked by a variety of motor disorders and neurological decline, is the second most common neurodegenerative disease worldwide. Currently, no diagnostic test exists to identify sufferers, and physicians must rely on a combination of subjective physical and neurological assessments to make a diagnosis. The discovery of definitive blood-borne biomarkers would be a major step towards early and reliable diagnosis. Despite attention devoted to this search, such biomarkers have remained elusive. In the present study, we used human protein microarrays to reveal serum autoantibodies that are differentially expressed among PD and control subjects. The diagnostic significance of each of these autoantibodies was evaluated, resulting in the selection of 10 autoantibody biomarkers that can effectively differentiate PD sera from control sera with a sensitivity of 93.1% and specificity of 100%. PD sera were also distinguishable from sera obtained from Alzheimer's disease, breast cancer, and multiple sclerosis patients with accuracies of 86.0%, 96.6%, and 100%, respectively. Results demonstrate that serum autoantibodies can be used as highly specific and accurate biomarkers for PD diagnosis throughout the course of the disease.

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

    Science.gov (United States)

    Pouladfar, Gholamreza; Jafarpour, Zahra; Pourabbas, Bahman; Geramizadeh, Bita; Dashti, Anahita Sanaei

    2016-01-01

    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. PMID:27418985

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  7. 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.

  8. Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

    DEFF Research Database (Denmark)

    Wuttge, D. M.; Carlsen, A. L.; Teku, G.;

    2015-01-01

    or more autoantibody groups, and five (miRNA-409, -184, -92a, -29a and -101) remained significant after correction for multiple comparisons. Multiple regression models accurately predicted ACA and anti-DNA topoisomerase I antibody positive patients (area under the curve (AUC) = 0.97 and 0.93, respectively...

  9. Anti-neutrophil cytoplasmic autoantibodies and leukocyte-endothelial interactions : a sticky connection?

    NARCIS (Netherlands)

    Heeringa, P; Huugen, D; Tervaert, JWC

    2005-01-01

    Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificity for myeloperoxidase (MPO) or proteinase 3 (Pr3) are associated with systemic small-vessel vasculitides (SVV). Detection of ANCA is an established clinical tool in disease diagnosis and monitoring. Based on clinical and in vitro exper

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  11. Autoantibody to glial fibrillary acidic protein in the sera of cattle with bovine spongiform encephalopathy.

    Science.gov (United States)

    Nomura, Sachiko; Miyasho, Taku; Maeda, Naoyuki; Doh-ura, Katsumi; Yokota, Hiroshi

    2009-08-01

    It is desirable to make the diagnosis in live cattle with bovine spongiform encephalopathy (BSE), and thus surrogate markers for the disease have been eagerly sought. Serum proteins from BSE cattle were analyzed by 2-D Western blotting and TOF-MS. Autoantibodies against proteins in cytoskeletal fractions prepared from normal bovine brains were found in the sera of BSE cattle. The protein recognized was identified to be glial fibrillary acidic protein (GFAP), which is expressed mainly in astrocytes in the brain. The antigen protein, GFAP, was also found in the sera of BSE cattle. The percentages of both positive sera in the autoantibody and GFAP were 44.0% for the BSE cattle, 0% for the healthy cattle, and 5.0% for the clinically suspected BSE-negative cattle. A significant relationship between the presence of GFAP and the expression of its autoantibody in the serum was recognized in the BSE cattle. These findings suggest a leakage of GFAP into the peripheral blood during neurodegeneration associated with BSE, accompanied by the autoantibody production, and might be useful in understanding the pathogenesis and in developing a serological diagnosis of BSE in live cattle.

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

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

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

  13. Frequency of autoantibodies and connective tissue diseases in Chinese patients with optic neuritis.

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    Hongyang Li

    Full Text Available BACKGROUND: Optic neuritis (ON is often associated with other clinical or serological markers of connective tissue diseases (CTDs. To date, the effects of autoantibodies on ON are not clear. PURPOSE: To assess the prevalence, clinical patterns, and short outcomes of autoantibodies and Sjögren's syndrome (SS involvement in Chinese ON patients and evaluate the relationship between ON, including their subtypes, and autoantibodies. METHODS: A total of 190 ON patients were divided into recurrent ON (RON, bilateral ON (BON, and isolated monocular ON (ION. Demographic, clinical, and serum autoantibodies data were compared between them with and without SS involvement. Serum was drawn for antinuclear antibody (ANA, extractable nuclear antigen antibodies (SSA/SSB, rheumatoid factor (RF, anticardiolipin antibodies (ACA, and anti-double-stranded DNA antibody (A-ds DNA, anticardiolipin antibody (ACLs, anti-β2-glycoprotein I (β2-GPI and Aquaporin-4 antibodies (AQP4-Ab. Spectral-domain optical coherence tomography (SD-OCT was used to evaluate the atrophy of the optic nerve. RESULTS: 68 patients (35.79% had abnormal autoantibodies, 26(13.68% patients met diagnostic criteria for CTDs, including 15(7.89% patients meeting the criteria for SS. Antibodies including SSA/SSB 23 (30.26% (p1 and p 2<0.001 and AQP4-Ab10 (13.16% (p1 = 0.044, p2 = 0.01 were significantly different in patients in the RON group when compared with those in the BON (P1 = RON VS ION and ION (p2 = RON VS ION groups. SS was more common in RON patients (p1 = 0.04, p2 = 0.028. There was no significant difference between SSA/SSB positive and negative patients in disease characteristics or severity. Similar results were obtained when SS was diagnosed in SSA/SSB positive patients. CONCLUSION: RON and BON were more likely associated with abnormal autoantibodies; furthermore, AQP4 antibody, SSA/SSB and SS were more common in the RON patients. AQP4 antibody determination is

  14. Rapid assays for detection of anti-islet autoantibodies: implications for organ donor screening.

    Science.gov (United States)

    Maniatis, A K; Yu, L; Miao, D; Nelson, K; Eisenbarth, G S

    2001-02-01

    The purpose of the current study was to develop and evaluate rapid assays for autoantibodies to GAD65 (GAA), ICA512bdc/IA-2 (ICA512AA), and insulin (microIAA, mIAA) as a potential tool for identification of cadaveric pancreas donors who were at high risk for developing diabetes. The study included 154 new onset diabetic, prediabetic, and healthy control subjects. Subjects were evaluated for all three autoantibodies in three separate assays: (1) standard (std) assay with a 24-h or 72-h incubation at 4 degrees C (combined GAA/ICA512AA or mIAA, respectively), (2) rapid assay with 1-h room temperature (RT) incubation, and (3) rapid assay with 2-h RT incubation. The serum samples from 777 organ donors were also evaluated for all three autoantibodies and all the positive samples from standard assay evaluated with the 1-h incubation assay. Simple linear regression analyses revealed excellent correlation between the standard assay and the rapid assays for all three autoantibodies, as follows: (1) GAA: std vs. 1 h (R2=0.85) and std vs. 2 h (R2=0.83), (2) ICA512AA: std vs. 1 h (R2=0.85) and std vs. 2 h (R2=0.84), and (3) mIAA: std vs. 1 h (R2=0.70) and std vs. 2 h (R2=0.64). Comparison of assay correlation rates between subject cohorts revealed no significant differences. Compared to their respective standard assays, the 1-h RT GAA assay missed 3.2% and identified an additional 1.3% of samples, the 1-h RT ICA512AA assay had no discordant samples, and the 1-h RT mIAA assay missed 7.1% and identified an additional 5.8% of samples. We analysed a series of 777 stored serum samples from cadaveric donors. Two of 777 (0.25%) were positive for two autoantibodies (both GAA and ICA512AA) and 23 of 777 (3.0%) one autoantibody (11 IAA; 12 GAA). The rapid analysis for all three autoantibodies could be completed in less than 3 h with comparable concordance rates to the more time-consuming standard assays, making these assays an attractive option for organ donor screening to identify

  15. Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Hua Zhou; Bin Zhang; Kemp H Kernstine; Li Zhong

    2011-01-01

    AIM: To evaluate the diagnostic values of serum autoantibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoantibodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested. RESULTS: The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-β-D-Thiogalactopyranoside (IPTG) induction at 37℃ for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples (OD450 = 1.69 ± 0.08 vs OD450 = 1.55 ± 0.10, P < 0.001). The area under the receiver operating characteristic (ROC) curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples (OD450 = 1.62 ± 0.06 vs OD450 = 1.55 ± 0.10, P < 0.001), the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60. CONCLUSION: Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma.

  16. Effects of Autoantibodies Against At1-receptor and Angiotensin II on Refractory Hypertension

    Institute of Scientific and Technical Information of China (English)

    廖玉华; 魏宇淼; 王敏; 董继华; 王朝晖; 苑海涛

    2001-01-01

    Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO -ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls.The mean age was 54. 3 ± 13 years old in RH group,53.5±9 years old in HT group and 51.2±11.9years old in normotensives (NT) group. The mean blood pressure was 154.2 ± 9.4/98.4 ± 8.2 mmHg in RH group and 130.1 ±7.6/80.5 ±6.7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8 ± 11.7/76. 4 ± 7.2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) Ⅱ were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15% ) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7.5 % ) normotensives, P < 0.01. Ang Ⅱwas 57.01 ± 52.63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 %) cases, both normal were 7 (17.9% ) cases, the autoantibodies positive or Ang Ⅱ in creasing was all of 14 (35.9 % ) cases (χ2 =0. 09,P > 0. 05) There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor antagnist used in the treatment of refractory hypertension might have an important value.

  17. Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy.

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    Kathrin Doppler

    Full Text Available Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients' sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.

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

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    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.

  19. 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.

  20. Comparison of different test systems for simultaneous autoantibody detection in connective tissue diseases.

    Science.gov (United States)

    Eissfeller, Petra; Sticherling, Michael; Scholz, Dietmar; Hennig, Kirsten; Lüttich, Tanja; Motz, Manfred; Kromminga, Arno

    2005-06-01

    The serological diagnosis of connective tissue diseases (CTDs) is based on the analysis of circulating autoantibodies to cytoplasmic and nuclear proteins (extractable nuclear antigens [ENAs]). The determination of autoantibody specificities supports the clinical diagnosis of the type of CTD and also often the prognosis of the disease. The former indirect immunofluorescence (IIF) technique still provides a useful screening method that currently is supplemented by a range of different techniques allowing the exact determination of single autoantibody specificities. These ENA profiling techniques include ELISA, immunoblotting, line-blot assays, and flow cytometric bead-based multiplex assays. The novel line immunoassay (LIA) from Mikrogen has been introduced in a recent study as a suitable technique for the simultaneous detection of autoantibodies in a routine clinical laboratory, providing comparable results as ELISA and ELiA (both from Pharmacia Diagnostics) (see Damoiseaux et al., this volume). In this study, LIAs from three different manufacturers were performed in 30 serum samples from patients with dermatological manifestations and 27 samples from SLE patients with renal involvement. The line assays from Mikrogen (recomLine ANA/ENA), Innogenetics (Inno-Lia ANA Update), and Imtec (ANA-LIA) were compared for antigen composition, handling, and statistical analysis including sensitivity and concordance. Autoantibody frequencies detected by the Mikrogen, Innogenetics, and Imtec line assays were 14.0%, 19.3%, and 15.8% for RNP; 14.0%, 22.8%, and 14.0% for Sm; 26.3%, 31.6%, and 40.3% for SSA; 3.5%, 12.3%, and 14.0% for SSB; and 3.5%, 14.0%, and 10.5% for histones. Our studies show that the line assay format is an easy-to-use, sensitive, and specific method for ENA antibody detection in human sera.

  1. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.

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    Vincent Plagnol

    2011-08-01

    Full Text Available The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC human leukocyte antigen (HLA region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP data in type 1 diabetes (T1D patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506, insulinoma-associated antigen 2 (IA-2A, n = 2,498, antibodies to the autoimmune thyroid (Graves' disease (AITD autoantigen thyroid peroxidase (TPOA, n = 8,300, and antibodies against gastric parietal cells (PCA, n = 4,328 that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10: 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A.

  2. 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.

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

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    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

  4. Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR.

    Science.gov (United States)

    Lin, F; Noyer, C M; Ye, Q; Courvalin, J C; Worman, H J

    1996-01-01

    Autoantibodies from rare patients with primary biliary cirrhosis (PBC) recognize LBR, or lamin B receptor, an integral membrane protein of the inner nuclear membrane. Human LBR has a nucleoplasmic, amino-terminal domain of 208 amino acids followed by a carboxyl-terminal domain with eight putative transmembrane segments. Autoantibodies against LBR from four patients with PBC recognized the nucleoplasmic, amino-terminal domain but not the carboxyl-terminal domain. Immunoblotting of smaller fusion proteins demonstrated that these autoantibodies recognized a conformational epitope(s) contained within the stretch of amino acids from 1 to 60. These results, combined with those of previous studies, show that autoepitopes of nuclear membrane proteins are located within their nucleocytoplasmic domains and that autoantibodies from patients with PBC predominantly react with one domain of a protein antigen. This work also provides further characterization of anti-LBR antibodies that have found utility as reagents in cell biology research.

  5. Genetic identification and functional validation of Fc gamma RIV as key molecule in autoantibody-induced tissue injury

    NARCIS (Netherlands)

    Kasperkiewicz, Michael; Nimmerjahn, Falk; Wende, Sabina; Hirose, Misa; Iwata, Hiroaki; Jonkman, Marcel F.; Samavedam, Unni; Gupta, Yask; Moeller, Steffen; Rentz, Ellen; Hellberg, Lars; Kalies, Kathrin; Yu, Xinhua; Schmidt, Enno; Haesler, Robert; Laskay, Tamas; Westermann, Juergen; Koehl, Joerg; Zillikens, Detlef; Ludwig, Ralf J.

    2012-01-01

    Autoantibody-mediated diseases are clinically heterogeneous and often fail conventional therapeutic strategies. Gene expression profiling has helped to identify new molecular pathways in these diseases, although their potential as treatment targets largely remains to be functionally validated. Based

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

    NARCIS (Netherlands)

    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; Shimizu, Hiroshi; Ludwig, Ralf J.

    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 inflamma

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

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    Debmalya Sanyal

    2017-01-01

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

  8. Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders.

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    John S Tzartos

    Full Text Available Autoantibodies against aquaporin-4 (AQP4, a water channel in CNS astrocytes, are detected in ∼50-80% of patients with neuromyelitis optica spectrum disorders (NMOsd, characterized by longitudinally extensive transverse myelitis (LETM and/or optic neuritis. Although these autoantibodies present an invaluable biomarker for NMOsd and for the differential diagnosis of multiple sclerosis (MS, diagnosis of anti-AQP4-seronegative NMOsd remains challenging. We hypothesized that seronegative NMOsd patients might have autoantibodies against aquaporin-1 (AQP1, another water channel in CNS astrocytes. We initially developed a radioimmunoprecipitation assay to search for anti-AQP1 antibodies in sera from 632 individuals. Anti-AQP1 or anti-AQP4 autoantibodies were detected in 16.7% and 12%, respectively, of 348 patients with suspected NMOsd. Anti-AQP1 specificity was confirmed by competition, protein immunoblotting and ELISA assays, whereas epitope localization was studied by immunoadsorption on intact cells expressing AQP1 and peptide mapping experiments. Most anti-AQP1 autoantibodies were of the complement-activating IgG1 subclass and the majority bound to the extracellular domain of AQP1, suggesting a possible pathogenic role. Five out of 42 MS patients had anti-AQP1 antibodies, but 2 of them also had spinal cord lesions, while the anti-AQP1 antibodies in the other 3 bound to the cytoplasmic domain of AQP1. Anti-AQP1 antibodies were not detected in 100 healthy individuals or 142 patients with non-demyelinating neuroimmune diseases. Analysis of 17 anti-AQP1+/anti-AQP4- patients with suspected NMOsd showed that 5 had NMO and 11 had LETM. 12/17 of these sera bound predominantly to the extracellular AQP1 loop-Α. Overall, we found that anti-AQP1 autoantibodies are present in a subgroup of patients with chronic demyelination in the CNS and similarities with anti-AQP4-seronegative NMOsd, offering a novel potential biomarker for CNS demyelination disorders.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

  11. 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;

    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....

  12. LEVELS OF NEUROSPECIFIC ENOLASE AND ENOLASE-SPECIFIC AUTOANTIBODIES IN BLOOD SERUM OF THE PATIENTS WITH AUTOIMMUNE THYROPATIES

    Directory of Open Access Journals (Sweden)

    N. N. Tsybikov

    2010-01-01

    Full Text Available The patients with autoimmune thyroiditis and various functional states of thyroid gland, and diffuse toxic goiter with pronounced thyrotoxicosis were studied for neurospecific enolase and enolase-specific autoantibodies levels in blood serum. Increased concentrations of neurospecific enolase and specific autoantibodies were revealed in all groups of the patients. A conclusion was drawn that nervous system may be involved into pathological process during development of thyropaties.

  13. Identification of the immunodominant epitope region in phospholipase A2 receptor-mediating autoantibody binding in idiopathic membranous nephropathy.

    Science.gov (United States)

    Kao, Liyo; Lam, Vinson; Waldman, Meryl; Glassock, Richard J; Zhu, Quansheng

    2015-02-01

    Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Recent clinical studies established that >70% of patients with idiopathic (also called primary) MN (IMN) possess circulating autoantibodies targeting the M-type phospholipase A2 receptor-1 (PLA2R) on the surface of glomerular visceral epithelial cells (podocytes). In situ, these autoantibodies trigger the formation of immune complexes, which are hypothesized to cause enhanced glomerular permeability to plasma proteins. Indeed, the level of autoantibody in circulation correlates with the severity of proteinuria in patients. The autoantibody only recognizes the nonreduced form of PLA2R, suggesting that disulfide bonds determine the antigenic epitope conformation. Here, we identified the immunodominant epitope region in PLA2R by probing isolated truncated PLA2R extracellular domains with sera from patients with IMN that contain anti-PLA2R autoantibodies. Patient sera specifically recognized a protein complex consisting of the cysteine-rich (CysR), fibronectin-like type II (FnII), and C-type lectin-like domain 1 (CTLD1) domains of PLA2R only under nonreducing conditions. Moreover, absence of either the CysR or CTLD1 domain prevented autoantibody recognition of the remaining domains. Additional analysis suggested that this three-domain complex contains at least one disulfide bond required for conformational configuration and autoantibody binding. Notably, the three-domain complex completely blocked the reactivity of autoantibodies from patient sera with the full-length PLA2R, and the reactivity of patient sera with the three-domain complex on immunoblots equaled the reactivity with full-length PLA2R. These results indicate that the immunodominant epitope in PLA2R is exclusively located in the CysR-FnII-CTLD1 region.

  14. Molecular analysis of snRNAs and scRNAs using autoantibodies from patients with systemic lupus erythematosus.

    Science.gov (United States)

    Flores, G; Martinez, F; Reyes, P A; Cortes, J J

    1997-01-01

    Immunoprecipitation analysis of total HeLa cells RNA extract by protein A-Sheparose purified autoantibodies and pCp 32P-3' end labeling RNAs revealed that U1, U2, U4 and U5 snRNAs are related with anti-Sm or U1nRNP autoantibodies, while the hY1, hY3, hY4 and hY5 scRNAs were related to anti-SSA/Ro autoantibodies present in sera of patients with Systemic Lupus Erythematosus. The authors detected molecular snRNAs and scRNAs specificities by autoantibodies in 71 sera, the molecular RNA specificity for anti-Sm (U1, U2, U4 and U5 snRNAs) was present in 39%; anti-SSA/Ro sera reacted against scRNAs (hY1, hY3, hY4 and hY5) in 36%, then anti-U1nRNP sera recognized U1 snRNA in 13% of sera and anti-rRNP related with rRNA were recognized in 8%. Twenty-nine SLE sera were RNA negative. A molecular characterization of the autoantibodies in sera from SLE patients may be a useful tool for clinical and laboratory diagnosis of SLE, and the use of autoantibodies as molecular probes allows to continue exploring some basic mechanism of gene expression.

  15. Research on Autoantibodies Against Myocardial β1-adrenergic and M2 Cholinergic Receptors in Patients With Chronic Keshan Disease

    Institute of Scientific and Technical Information of China (English)

    Han Zhenhua; Niu Xiaolin; Ren Fuxian

    2006-01-01

    Objectives To explore the relationship between serum autoantibodies against myocardial β1-adrenergic, M2-cholinergic receptors and chronic Keshan disease (CKD). Methods The second extracellular loops of β1 and M2 receptors on human cardiomyocytes were used as the antigens.Enzyme linked immunosorbent assay (ELISA) was applied to determine serum autoantibodies against myocardial β1 and M2 receptors in 32 CKD patients. 31 healthy subjects from endemic area were selected as the control. Results Positive rate of autoantibodies against myocardial β1 adrenergic (51.3%, 17/32) and M2cholinergic (56.3% , 18/32) receptors weresignificantly higher than those in the control (9.7%, 3/31; 12.9%, 4/31) (both P < 0.01). Both positive rate and titers of above autoantibodies in NYHA Ⅱ~Ⅲ CKD patients were significantly higher than those in NYHA Ⅳ , demonstrating an apparently positive correlation between serum antibodies against myocardial β1 and M2 receptors (r=0.95). Conclusions Autoantibodies against myocardial β1 and M2 receptors were found in sera of CKD patients; distribution of positive rate and titers of the autoantibodies in CKD patients in various NYHA classes of cardiac function are significantly different.

  16. Identification of autoantibody against fatty acid synthase in hepatocellular carcinoma mouse model and its application to diagnosis of HCC.

    Science.gov (United States)

    Heo, Chang-Kyu; Woo, Mi-Kyung; Yu, Dae-Yeul; Lee, Ju Yeon; Yoo, Jong Shin; Yoo, Hyang Sook; Ko, Jeong Heon; Kim, Jin-Man; Choi, Jong Young; Kim, In Gyu; Paik, Sang Gi; Cho, Eun-Wie

    2010-06-01

    Autoantibodies, which are generated by immune system recognizing the presence of the abnormal tumor-associated antigens, are promising biomarkers for early detection of tumors. Recently, we established a B cell hybridoma pool derived from H-ras12V transgenic mouse, a typical hepatocellular carcinoma model, as a source of tumor-associated autoantibodies without using any extracellular antigens and have characterized the specific target antigens against them. K1 autoantibody, one of them, was investigated in this study and its target antigen was identified by mass spectrometric analysis as fatty acid synthase (FASN), an important oncogenic protein. Moreover, a specific mimotope against K1 autoantibody was screened from the cyclic random hepta-peptide phage library and, using it as a coating antigen for ELISA, we could distinguish patients with hepatocellular carcinoma (HCC) vs. normal subjects with 96.55% sensitivity and 100% specificity. These results imply that anti-FASN autoantibody is induced in patients with HCC and detection of anti-FASN autoantibody can be used for the diagnosis of HCC.

  17. Changes in Autoantibodies against β1-Adrenoceptor and M2-Muscarinic Receptor during Development of Renovascular Hypertension in Rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Ming ZHI; Rong-Fang CHEN; Heng WU; Hui-Rong LIU; Rong-Rui ZHAO

    2004-01-01

    In an experimental rat's renovascular hypertension model, we studied the genesis of anticardiac β1-adrenoceptor and M2-muscarinic receptor autoantibodies in relation to the changes in immunological function during the development of renal hypertension. The biological activities of these autoantibodies were also examined. It was shown that after two weeks of operation both the frequency of occurrence and the titre of autoantibodies to cardiac β1-adrenoceptor and M2-muscarinic receptor were significantly increased as compared with the control of pre-treatment. The increased autoantibodies lasted for several weeks and then automatically decreased gradually to the pre-clipping level at 10 weeks. Meanwhile the ratio of CD4+/CD8+was also undergone an initial increase followed by gradual recovery and correlated well with the changes in antibody titre. The biological effects of these autoantibodies displayed an "agonistic-like" activities on the beating frequency of cultured neonatal cardiomyocyte. It is suggested that autoimmune mechanisms are involved in the pathogenesis of renal hypertension and the cardiac receptor autoantibodies might be one of the mechanisms leading to cardiac dysfunction.

  18. Association of reversible splenial lesion syndrome (RESLES) with Anti-VGKC autoantibody syndrome: a case report.

    Science.gov (United States)

    Gilder, Thomas R; Hawley, Jason S; Theeler, Brett J

    2016-05-01

    A 50-year-old male presented with complaints of fatigue, confusion, and memory problems. Neurological evaluation revealed altered cognition, unsteady gait, ataxia, dysmetria, and weakness. MRI of the brain was initially unremarkable. Over several days, the patient experienced improvement of symptoms and a follow-up MRI revealed a small lesion in the splenium of the corpus callosum seen on diffusion weighted and T2 sequences. The patient was discovered to have elevated anti-voltage gated potassium channel serum autoantibodies. Follow-up MRI revealed resolution of the splenial lesion. The patient was treated with intravenous immune globulin, and improved back to his pre-treatment baseline. We believe this to be the first case of a reversible splenial lesion syndrome as a manifestation of the anti-voltage gated potassium channel autoantibody syndrome, and propose a pathophysiologic mechanism.

  19. 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.

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

    Science.gov (United States)

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

    2013-03-15

    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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Pilar eMartinez-Martinez

    2013-09-01

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

  3. Tobacco exposure and diabetes-related autoantibodies in children: results from the ABIS study.

    Science.gov (United States)

    Johansson, Annakarin; Hermansson, Göran; Ludvigsson, Johnny

    2008-12-01

    Passive smoking has decreased in recent years ("increased hygiene"). Less environmental tobacco smoke (ETS) gives increased hygiene that, if the hygiene hypothesis is true, in turn might give more autoimmune diseases. The presence of auto antibodies is considered to be an early indicator of type 1 diabetes (T1D). Because tobacco exposure may influence the immune system, we analyzed the relation between passive smoking and development of autoantibodies. A subsample (n= 8794) of the children in the ABIS study was used for this analysis. The parents answered questionnaires on smoking from pregnancy and onwards, and blood samples from the children aged 2.5-3 years were analyzed for GADA and IA-2A. Results showed that there was no significant difference in the prevalence of GADA or IA-2A (>95 percentile) between tobacco-exposed and nonexposed children. It was concluded that passive smoking does not seem to influence development of diabetes-related autoantibodies early in life.

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

    Directory of Open Access Journals (Sweden)

    Ludwig Nicole

    2010-11-01

    Full Text Available Abstract Background 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. Methods 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. Result 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. Conclusion 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

  5. Paving the Way to Understand Autoantibody-Mediated Epilepsy on the Molecular Level.

    Science.gov (United States)

    Seebohm, Guiscard; Piccini, Ilaria; Strutz-Seebohm, Nathalie

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guiscard eSeebohm

    2015-07-01

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

  7. 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.

  8. Identification of autoantibodies against transthyretin for the screening and diagnosis of rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Saurabh Sharma

    Full Text Available Rheumatoid arthritis (RA is a chronic, autoimmune, systemic and inflammatory rheumatic disease that leads to inflammation of the joints and surrounding tissues. Identification of novel protein(s associated with severity of RA is a prerequisite for better understanding of pathogenesis of this disease that may also have potential to serve as novel biomarkers in the diagnosis of RA. Present study was undertaken to compare the amount of autoantigens and autoantibodies in the plasma of RA patients in comparison to healthy controls. Plasma samples were collected from the patients suffering from RA, Osteoarthritis (OA, Systemic lupus erythematosus (SLE and healthy volunteers. The screening of plasma proteins were carried out using 2-dimensional gel electrophoresis followed by identification of differentially expressed protein by MALDI-TOF MS/MS. Among several differentially expressed proteins, transthyretin (TTR has been identified as one of the protein that showed significantly up regulated expression in the plasma of RA patients. The results were further validated by Western blot analysis and ELISA. In comparison to OA synovium, an exclusive significantly high expression of TTR in RA has been validated through IHC, Western blotting and IEM studies. Most importantly, the increase in expression of TTR with the progression of severity of RA condition has been observed. The autoantibodies against TTR present in the RA plasma were identified using immunoprecipitation-Western methods. The significant production of autoantibodies was validated by ELISA and Western blot analysis using recombinant pure protein of TTR. Hence, these novel observations on increase in TTR expression with the increase in severity of RA conditions and significant production of autoantibodies against TTR clearly suggest that a systematic studies on the role TTR in the pathogenesis of RA is immediately required and TTR may be used as a serum diagnostic marker together with other

  9. 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

    % had anti-striated muscle antibodies. None of the control subjects had any muscle antibodies. There was no significant difference in frequency of the remaining autoantibodies between the groups investigated. The present study indicates autoimmune responses in PFS against antigens of the diseased tissue...... itself, a finding which may be secondary to the disease or have relevance to the still obscure pathogenesis of the syndrome....

  10. 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.

  11. Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy.

    Science.gov (United States)

    Oh, Yun Jung; Yang, Seung Hee; Kim, Dong Ki; Kang, Shin-Wook; Kim, Yon Su

    2013-01-01

    The data were presented in abstract form at the 45(th) meeting of the American Society of Nephrology, October 30-November 04 2012, San Diego, CA, USA. Circulating autoantibodies against M-type phospholipase A2 receptor (PLA2R) are important pathogenic antibodies of idiopathic membranous nephropathy (MN) in adults. However, previous studies on the clinical impact of anti-PLA2R antibodies demonstrated several limitations, including insufficient numbers of study subjects and different time points and methods for anti-PLA2R antibody measurement. To verify the clinical significance of anti-PLA2R antibodies in Korean patients with MN, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 100 patients with idiopathic MN who had not yet received immunosuppressive treatment. We detected anti-PLA2R antibody in 69 patients, and we observed that autoantibody reactivity reflected the severity of disease activity. Proteinuria and hypoalbuminemia were more severe in patients with anti-PLA2R than in those without the autoantibodies (2.95 g/g vs. 6.85 g/g, P = 0.003; 3.1 g/dL vs. 2.5 g/dL, P = 0.004, respectively). Additionally, the clinical severities worsened proportionally as the levels of anti-PLA2R antibodies increased (P = 0.015 and P for trend PLA2R antibody showed a significant correlation with clinical outcomes, such as remission rate and time to remission. In conclusion, we observed that anti-PLA2R antibodies are highly prevalent in Korean patients with idiopathic MN and that they reflect the clinical disease activity before the administration of immunosuppressive treatment. However, the levels of anti-PLA2R antibody at the time of kidney biopsy may not predict the clinical outcomes in current clinical practice.

  12. Identification of a major epitope recognized by PLA2R autoantibodies in primary membranous nephropathy.

    Science.gov (United States)

    Fresquet, Maryline; Jowitt, Thomas A; Gummadova, Jennet; Collins, Richard; O'Cualain, Ronan; McKenzie, Edward A; Lennon, Rachel; Brenchley, Paul E

    2015-02-01

    Phospholipase A2 receptor 1 (PLA2R) is a target autoantigen in 70% of patients with idiopathic membranous nephropathy. We describe the location of a major epitope in the N-terminal cysteine-rich ricin domain of PLA2R that is recognized by 90% of human anti-PLA2R autoantibodies. The epitope was sensitive to reduction and SDS denaturation in the isolated ricin domain and the larger fragment containing the ricin, fibronectin type II, first and second C-type lectin domains (CTLD). However, in nondenaturing conditions the epitope was protected against reduction in larger fragments, including the full-length extracellular region of PLA2R. To determine the composition of the epitope, we isolated immunoreactive tryptic fragments by Western blotting and analyzed them by mass spectrometry. The identified peptides were tested as inhibitors of autoantibody binding to PLA2R by surface plasmon resonance. Two peptides from the ricin domain showed strong inhibition, with a longer sequence covering both peptides (31-mer) producing 85% inhibition of autoantibody binding to PLA2R. Anti-PLA2R antibody directly bound this 31-mer peptide under nondenaturing conditions and binding was sensitive to reduction. Analysis of PLA2R and the PLA2R-anti-PLA2R complex using electron microscopy and homology-based representations allowed us to generate a structural model of this major epitope and its antibody binding site, which is independent of pH-induced conformational change in PLA2R. Identification of this major PLA2R epitope will enable further therapeutic advances for patients with idiopathic membranous nephropathy, including antibody inhibition therapy and immunoadsorption of circulating autoantibodies.

  13. Detection of autoantibodies to DSF70/LEDGFp75 in Mexican Hispanics using multiple complementary assay platforms

    OpenAIRE

    Vázquez-del Mercado, Mónica; Gómez-Bañuelos, Eduardo; Navarro-Hernández, Rosa Elena; Pizano-Martinez, Oscar; Saldaña-Millán, Adan; Chavarria-Avila, Efrain; Gonzalez-Rosas, Lorena; Andrade-Ortega, Lilia; Saavedra, Miguel Angel; Vera-Lastra, Olga Lidia; Jara, Luis Javier; Medrano-Ramírez, Gabriel; Cruz-Reyes, Claudia; García-De La Torre, Ignacio; Escarra-Senmarti, Marta

    2016-01-01

    Purpose Antinuclear autoantibodies (ANA) targeting the dense fine speckled antigen DFS70, also known as lens epithelium-derived growth factor p75 (LEDGF/p75), are attracting attention due to their low frequency in systemic rheumatic diseases but increased frequency in clinical laboratory referrals and healthy individuals (HI). These ANA specifically recognize the stress protein DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their frequency has been investigated in var...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-10-01

    TSH-receptor-auto antibodies were determined in follow-up of 30 patients with relapse of toxic diffuse goitres, i.e. patients with Graves' disease and toxic disseminated autonomy, and in 13 patients with spontaneous remission after antithyroid drug therapy by use of a commercially available TSH-radioreceptorassay (TRAK-assay). All the patients with very high receptor-autoantibody-titers in untreated thyrotoxicosis (F > 20%) had one or more periods of hyperthyroidism or a very severe course of disease. None of these patients showed a spontaneous remission of disease. They all could be identified as Graves' patients. Patients with TRAK-titers 3% <= 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.

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

    OpenAIRE

    Takashi Himoto; Tsutomu Masaki

    2012-01-01

    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 antin...

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

    Science.gov (United States)

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

    2015-10-15

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

  17. 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.

  18. 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.

  19. 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.

  20. Autoantibodies against nuclear, nucleolar, and mitochondrial antigens in systemic sclerosis (scleroderma).

    Science.gov (United States)

    Reimer, G

    1990-02-01

    One of the most characteristic serologic features of systemic sclerosis (scleroderma) is the occurrence of autoantibodies against nuclear and most notably against nucleolar antigens. This humoral autoimmune response is one of best studied immunologic phenomena in scleroderma. Detailed molecular information on the structure and function, as well as on reactive epitopes of autoantigens targeted by specific serum antibodies, has been revealed by clinical, immunologic, and biochemic studies in several laboratories. Autoantigens such as DNA topoisomerase I (Scl-70), centromere proteins, RNA polymerase I, U3 RNP-associated fibrillarin, PM-Scl, and 7-2 RNP antigens were shown to be specific targets of scleroderma patients and were observed to have clinical correlates within the scleroderma disease spectrum. Therefore, autoantibodies in scleroderma are not only valuable diagnostic tools but also prognosticators of the disease. Although autoantibodies in scleroderma do not appear to play a pathogenetic role in the disease process, the knowledge of the structure and function of their reactive antigens may help in answering questions concerning the etiology of the disease.

  1. 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

    2015-12-01

    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.

  2. Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations.

    Science.gov (United States)

    von Gunten, Stephan; Schaub, Alexander; Vogel, Monique; Stadler, Beda M; Miescher, Sylvia; Simon, Hans-Uwe

    2006-12-15

    Human intravenous immunoglobulin (IVIg) preparations are increasingly used for the treatment of autoimmune diseases. Earlier work demonstrated the presence of autoantibodies against Fas in IVIg, suggesting that IVIg might be able to induce caspase-dependent cell death in Fas-sensitive cells. In this study, we demonstrate that sialic acid-binding Ig-like lectin 9 (Siglec) represents a surface molecule on neutrophils that is activated by IVIg, resulting in caspase-dependent and caspase-independent forms of cell death. Neutrophil death was mediated by naturally occurring anti-Siglec-9 autoantibodies present in IVIg. Moreover, the efficacy of IVIg-mediated neutrophil killing was enhanced by the proinflammatory cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma), and this additional cell death required reactive oxygen species (ROSs) but not caspases. Anti- Siglec-9 autoantibody-depleted IVIg failed to induce this caspase-independent neutrophil death. These findings contribute to our understanding of how IVIg preparations exert their immunoregulatory effects under pathologic conditions and may provide a possible explanation for the neutropenia that is sometimes seen in association with IVIg therapy.

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

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Hua-Ling Ruan; Yi Lia Min Zhang; Chang-Jun Zhao

    2016-01-01

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

  4. Autoantibodies in Renal Diseases – Clinical Significance and Recent Developments in Serological Detection

    Science.gov (United States)

    Mastroianni-Kirsztajn, Gianna; Hornig, Nora; Schlumberger, Wolfgang

    2015-01-01

    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. PMID:26029207

  5. Frequency of islet cell autoantibodies (IA-2 and GAD in young Brazilian type 1 diabetes patients

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    V.C. Pardini

    1999-10-01

    Full Text Available Type 1 diabetes, as an autoimmune disease, presents several islet cell-specific autoantibodies such as islet cell antibody (ICA, anti-insulin, anti-glutamic acid decarboxylase (GAD and the antibody (Ab against tyrosine phosphatase (PTP-like protein known as ICA-512 (IA-2. In order to determine the frequency of the anti-GAD and anti-IA-2 autoantibodies in Brazilian type 1 diabetes patients we studied 35 diabetes mellitus (DM type 1 patients with recent-onset disease (£12 months and 37 type 1 diabetes patients with long-duration diabetes (>12 months who were compared to 12 children with normal fasting glucose. Anti-GAD65 and anti-IA-2 autoantibodies were detected with commercial immunoprecipitation assays. The frequency of positive results in recent-onset DM type 1 patients was 80.0% for GADAb, 62.9% for IA-2Ab and 82.9% for GADAb and/or IA-2Ab. The long-duration type 1 diabetes subjects presented frequencies of 54.1% for GADAb and IA-2Ab, and 67.5% for GAD and/or IA-2 antibodies. The control group showed no positive cases. Anti-GAD and IA-2 assays showed a high frequency of positivity in these Brazilian type 1 diabetes patients, who presented the same prevalence as a Caucasian population.

  6. 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

    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....

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

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    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

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

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    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.

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

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    Annekathrin Haberland

    2013-02-01

    Full Text Available 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.

  10. Differential clearance mechanisms, neutrophil extracellular trap degradation and phagocytosis, are operative in systemic lupus erythematosus patients with distinct autoantibody specificities.

    Science.gov (United States)

    Chauhan, Sudhir Kumar; Rai, Richa; Singh, Vikas Vikram; Rai, Madhukar; Rai, Geeta

    2015-12-01

    Systemic lupus erythematosus (SLE) patients are generally presented with autoantibodies against either dsDNA or RNA-associated antigens (also known as extractable nuclear antigens, ENA) or both. However, the mechanisms and processes that lead to this distinctive autoantibody profile are not well understood. Defects in clearance mechanism i.e. phagocytosis may lead to enhanced microbial and cellular debris of immunogenic potential. In addition to defective phagocytosis, impaired neutrophil extracellular trap (NET) degradation has been recently reported in SLE patients. However, the extent to which both these clearance processes (NET-degradation and phagocytosis) are operative in serologically distinguished subsets of SLE patients is not established. Therefore, in this report, we evaluated NET-degradation and phagocytosis efficiency among SLE patients with different autoantibody specificities. SLE patients were classified into three subsets based on their autoantibody profile (anti-dsDNA, anti-ENA or both) as determined by ELISA. NET-degradation by SLE and control sera was assessed by sytox orange-based fluorescence assay. Neutrophil-mediated phagocytosis in the presence of SLE and control sera was determined by flowcytometry. The segregation of SLE patients revealed significant differences in NET-degradation and phagocytosis in SLE patients with autoantibodies against dsDNA and ENA. We report that NET-degradation efficiency was significantly impaired in SLE patients with anti-dsDNA autoantibodies and not in those with anti-ENA autoantibodies. In contrast to NET-degradation, neutrophil-mediated phagocytosis was impaired in all three subsets independent of autoantibody specificity. These observations suggest that varying clearance mechanisms are operative in SLE subsets with anti-dsDNA or anti-ENA autoantibodies. The results outlined in this manuscript also suggest that sub-grouping of SLE patients could be useful in delineating the molecular and pathological

  11. Human smooth muscle autoantibody. Its identification as antiactin antibody and a study of its binding to "nonmuscular" cells.

    Science.gov (United States)

    Gabbiani, G; Ryan, G B; Lamelin, J P; Vassalli, P; Majno, G; Bouvier, C A; Cruchaud, A; Lüscher, E F

    1973-09-01

    When human serum containing smooth muscle autoantibodies (SMA) is incubated with extracts containing thrombosthenin (the contractile material of platelets) or thrombosthenin-A (the actin-like moiety of thrombosthenin), it loses its ability to bind to smooth muscle. Such binding is also diminished when SMA serum is incubated with lysed platelets; this effect is not seen if the SMA serum is incubated with intact platelets. The incubation of other autoantibodies (such as antimitochondrial or antinuclear antibodies) with thrombosthenin does not affect their binding to the specific antigens. It appears that SMA is directed against the actin fraction of thrombosthenin-ie, SMA is an antiactin antibody. Hence the name of antiactin autoantibody (AAA) seems more appropriate than smooth muscle autoantibody (SMA). A study of the distribution of antiactin autoantibody binding in rat, rabbit and man shows that several "nonmuscular" structures contain actin under normal conditions; these include megakaryocytes and platelets, normal rat hepatocytes, the brush borders of renal tubules, the periphery of epithelial cells of the intestine, polymorphs and lymphocytes in lymph nodes (but not thymic cortical lymphocytes). In addition, certain cell types (such as granulation tissue fibroblasts, cultivated fibroblasts, hepatocytes or regenerating liver and epidermal cells growing over a skin wound) can reversibly acquire a massive network of actin-containing microfilaments resembling those in smooth muscle.

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

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    Ioannis Ilias

    2015-01-01

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

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

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    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.

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

    Science.gov (United States)

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

    2015-09-25

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

  15. Autoantibodies against the catalytic domain of BRAF are not specific serum markers for rheumatoid arthritis.

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    Wenli Li

    Full Text Available BACKGROUND: Autoantibodies to the catalytic domain of v-raf murine sarcoma viral oncogene homologue B1 (BRAF have been recently identified as a new family of autoantibodies involved in rheumatoid arthritis (RA. The objective of this study was to determine antibody responses to the catalytic domain of BRAF in RA and other autoimmune diseases. The association between RA-related clinical indices and these antibodies was also assessed. METHODOLOGY/PRINCIPAL FINDINGS: The presence of autoantibodies to the catalytic domain of BRAF (anti-BRAF or to peptide P25 (amino acids 656-675 of the catalytic domain of BRAF; anti-P25 was determined in serum samples from patients with RA, primary Sjögren's syndrome (pSS, systemic lupus erythematosus (SLE, and healthy controls by using indirect enzyme-linked immunosorbent assays (ELISAs based on the recombinant catalytic domain of BRAF or a synthesized peptide, respectively. Associations of anti-BRAF or anti-P25 with disease variables of RA patients were also evaluated. Our results show that the BRAF-specific antibodies anti-BRAF and anti-P25 are equally present in RA, pSS, and SLE patients. However, the erythrocyte sedimentation rate (ESR used to detect inflammation was significantly different between patients with and without BRAF-specific antibodies. The anti-BRAF-positive patients were found to have prolonged disease, and active disease occurred more frequently in anti-P25-positive patients than in anti-P25-negative patients. A weak but significant correlation between anti-P25 levels and ESRs was observed (r = 0.319, p = 0.004. CONCLUSIONS/SIGNIFICANCE: The antibody response against the catalytic domain of BRAF is not specific for RA, but the higher titers of BRAF-specific antibodies may be associated with increased inflammation in RA.

  16. Sequential elevation of autoantibodies to thyroglobulin and glutamic acid decarboxylase in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Eiji; Kawasaki; Jun-ichi; Yasui; Masako; Tsurumaru; Haruko; Takashima; Toshiyuki; Ikeoka; Fumi; Mori; Satoru; Akazawa; Ikuko; Ueki; Masakazu; Kobayashi; Hironaga; Kuwahara; Norio; Abiru; Hironori; Yamasaki; Atsushi; Kawakami

    2013-01-01

    We have previously reported the high levels of glutamic acid decarboxylase 65 autoantibodies(GAD65A)in patients with type 1 diabetes and autoimmune thyroid disease.Here we describe a 32-year-old Japanese female with a thirteen-year history of type 1 diabetes whose levels of GAD65A were elevated just after the emergence of anti-thyroid autoimmunity.At 19 years of age,she developed diabetic ketoacidosis and was diagnosed with type 1 diabetes.She had GAD65A,insulinoma-associated antigen-2 autoantibodies(IA-2A),and zinc transporter-8 autoantibodies(ZnT8A),but was negative for antibodies to thyroid peroxidase(TPOAb)and thyroglobulin(TGAb)at disease onset.ZnT8A and IA-2A turned negative 2-3 years after the onset,whereas GAD65A were persistently positive at lower level(approximately 40 U/mL).However,just after the emergence of TGAb at disease duration of 12.5 years,GAD65A levels were reelevated up to5717 U/mL in the absence of ZnT8A and IA-2A.Her thyroid function was normal and TPOAb were consistently negative.She has a HLA-DRB1*03:01/*04:01-DQB1*02:01/*03:02 genotype.Persistent positivity for GAD65A might be associated with increased risk to develop anti-thyroid autoimmunity.

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

    Directory of Open Access Journals (Sweden)

    Isabela Siloşi

    2016-01-01

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

  18. Doubly Reactive INS-IGF2 Autoantibodies in Children with Newly Diagnosed Autoimmune (type 1) Diabetes.

    Science.gov (United States)

    Kanatsuna, N; Delli, A; Andersson, C; Nilsson, A-L; Vaziri-Sani, F; Larsson, K; Carlsson, A; Cedervall, E; Jönsson, B; Neiderud, J; Elding Larsson, H; Ivarsson, S-A; Törn, C; Fex, M; Lernmark, Å

    2015-10-01

    The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P INS-IGF2A when the cut-off was the 95th percentile of the controls (P INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.

  19. Characterization of a new highly sensitive immunometric assay for thyroglobulin with reduced interference from autoantibodies.

    Science.gov (United States)

    Broughton, Marianne Nordlund; Nome, Ragnhild; Sandven, Ingvill; Paus, Elisabeth; Bjøro, Trine

    2016-06-01

    Measurements of serum thyroglobulin (Tg) with sensitive immunoassays are of great importance for the management of patients with differentiated thyroid carcinomas. However, interference of circulating autoantibodies to Tg (hTgAb) hampers the usefulness of most assays. We have produced a panel of monoclonal antibodies (mAbs) selected to bind Tg in the presence of Tg autoantibodies and developed a sensitive immunoassay for Tg with minor interference by hTgAbs. The antibodies were characterized by cross-inhibition and immunoassay combination studies, as well as affinity estimation. The within-run and total imprecision of the assay were determined with 2664 samples in 60 separate runs. The most sensitive assay combination with superior protection against autoantibodies consisted of two solid phase mAbs and two tracer mAbs with distinct binding sites. The assay was linear and displayed a wide dynamic range up to 1342 μg/l with a functional sensitivity of 0.1 μg/l and a total imprecision of less than 10 %. There was good agreement between the new high sensitive immunofluorometric assay (IFMA) and two well-established Tg assays from Brahms Kryptor and Roche Diagnostics. Mean difference between the new IFMA and the Kryptor assay was 0.059 μg/l with a 95 % confidence interval of -0.032 to 0.151 μg/l, whereas the mean difference between the new IFMA and the Roche assay was -0.80 μg/l with a 95 % confidence interval of -1.24 to -0.35 μg/l.

  20. No Contribution of GAD-65 and IA-2 Autoantibodies around Time of Diagnosis to the Increasing Incidence of Juvenile Type 1 Diabetes

    DEFF Research Database (Denmark)

    Thorsen, Steffen U.; Pipper, Christian B.; Mortensen, Henrik B.;

    2016-01-01

    Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D) has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinom...

  1. Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old.

    Science.gov (United States)

    Ludvigsson, Johnny; Wahlberg, Jeanette

    2002-04-01

    Autoantibodies found in cord blood in children who later develop diabetes might be produced by the fetus. If so, continuous autoantibody production would still be expected in these children at one year of age. We decided to determine autoantibodies in cord blood and to see whether they persisted in these children at one year. Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. We conclude that most autoantibodies found in cord blood samples of children are probably passively transferred from mother to child. Antibody screening of cord blood cannot be used to predict diabetes in the general population. Infections during pregnancy may initiate an immune process related to diabetes development.

  2. Cytokines, autoantibodies and viral antibodies in premorbid and postdiagnostic sera from patients with rheumatoid arthritis: case-control study nested in a cohort of Norwegian blood donors

    DEFF Research Database (Denmark)

    Jørgensen, K T; Wiik, A; Pedersen, M;

    2008-01-01

    To assess the timing of changes in cytokines, cytokine-related markers, autoantibodies and viral antibodies in the pathogenesis of rheumatoid arthritis (RA).......To assess the timing of changes in cytokines, cytokine-related markers, autoantibodies and viral antibodies in the pathogenesis of rheumatoid arthritis (RA)....

  3. 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...

  4. Increased prevalence of autoimmune disorders and autoantibodies in parents of children with opsoclonus-myoclonus syndrome (OMS).

    Science.gov (United States)

    Krasenbrink, I; Fühlhuber, V; Juhasz-Boess, I; Stolz, E; Hahn, A; Kaps, M; Hero, B; Blaes, F

    2007-06-01

    Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease in childhood which can be associated with neuroblastoma. Since autoantibodies have been detected in some patients with OMS, an autoimmune etiology is suspected. We compared the prevalence of autoimmune disorders and autoantibodies in parents of children with OMS and in a group of controls of same age and sex. Autoimmune diseases were found in 15.8% of the parents of OMS children, but only in 2.0% of the controls (pOMS parents (42.8% vs. 8.0%, pOMS parents also had significantly more autoantibodies against CNS structures than the controls (pOMS and may also hint to a genetic susceptibility for OMS.

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

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo; Bahnsen, M;

    1981-01-01

    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...

  6. Autoantibodies against bromelainized mouse erythrocyte: strain distribution of serum idiotype expression and relative peritoneal cell activity.

    Science.gov (United States)

    Kaushik, A; Poncet, P; Bussard, A

    1986-10-15

    Previously, we demonstrated that the naturally occurring mouse autoantibodies directed against bromelainized mouse red blood cells (BrMRBC) comprised a family of structurally related molecules bearing a common idiotypic determinant (CP) based on structural and idiotypic analysis of a series of anti-BrMRBC monoclonal autoantibodies derived from a fusion of peritoneal cells (PerC) with plasmacytomas. In the present studies, we have evaluated the quantitative expression of circulating CP idiotype related to autoantibodies against BrMRBC in relation to specific PerC anti-BrMRBC plaque-forming activity in an individual mouse of different strains. The data presented here show no direct relationship between serum CP idiotype expression and PerC anti-BrMRBC plaque-forming activity in an individual mouse of all strains tested. However, the circulating CP idiotype content is higher in strains, viz., CBA/J, NZB, C3H, BXSB, and Biozzi high responder (H) mice which exhibit a high perC autoantibody secretory activity against BrMRBC. The strains such as BALB/c, DBA2, SJL/J, CBA/N, and Biozzi low responder (L) express little or no circulating CP idiotype with a corresponding small or no PerC anti-BrMRBC activity. Furthermore, the PerC "auto"-immune phenomenon is markedly expressed in the normal CBA/J strain since these mice show a higher percentage ratio of CP idiotype over serum IgM (2.68%) as well as highest PerC anti-BrMRBC plaque-forming activity (11,319 +/- 18,029 plaques per million viable cells) compared to other normal and autoimmune strains tested. Nevertheless, the highest circulating serum CP idiotype (49.4 micrograms/ml) is observed in the autoimmune NZB mouse. The immunodeficient CBA/N mice fail to express detectable levels of CP idiotype in their serum. The experiments conducted in genetically selected outbred Biozzi (H and L) strain have revealed remarkable differences in serum CP idiotype expression as well as PerC anti-BrMRBC plaque-forming activity in these two

  7. GAD65 epitope mapping and search for novel autoantibodies in GAD-associated neurological disorders.

    Science.gov (United States)

    Fouka, P; Alexopoulos, H; Akrivou, S; Trohatou, O; Politis, P K; Dalakas, M C

    2015-04-15

    Antibodies against Glutamic-acid-decarboxylase (GAD65) are seen in various CNS excitability disorders including stiff-person syndrome, cerebellar ataxia, encephalitis and epilepsy. To explore pathogenicity, we examined whether distinct epitope specificities or other co-existing antibodies may account for each disorder. The epitope recognized by all 27 tested patients, irrespective of clinical phenotype, corresponded to the catalytic core of GAD. No autoantibodies against known GABAergic antigens were found. In a screen for novel specificities using live hippocampal neurons, three epilepsy patients, but no other, were positive. We conclude that no GAD-specific epitope defines any neurological syndrome but other antibody specificities may account for certain phenotypes.

  8. 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...

  9. CLINICAL DIAGNOSTIC VALUE OF AUTOANTIBODIES IN THE DIAGNOSIS OF AUTOIMMUNE LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    V. V. Bazarnyi

    2015-01-01

    Full Text Available We are studied the 15 patients with autoimmune liver diseases and 36 patients without autoimmune pathology found the diagnostic value of antinuclear and antimitochondrial autoantibodies (AMA-M2 tests, and antibodies to asialoglycoprotein receptor (anti-ASGPR. Based on the ROC analysis showed that the diagnostic sensitivity and diagnostic specificity of AMA-M2 was 73% and 100% and for anti-ASGPR – 60% and 77%, respectively. Therefore, the test for anti-ASGPR in autoimmune diseases of the liver showed no advantages over standart tests, and its using in clinical practice requires clarification. 

  10. 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...

  11. Binding of circulating autoantibodies in breast cancer to native and peroxynitrite-modified RNA

    Institute of Scientific and Technical Information of China (English)

    Sheereen TARANNUM; Zarina ARIF; Khursheed ALAM

    2013-01-01

    Peroxynitrite (ONOO-) is a powerful oxidant and nitrosative agent and has in vivo existence.The half life of ONOO-at physiological pH is less than 1 s.It can react with nucleic acids,proteins,lipoproteins,saccharides,cardiolipin,etc.,and can modify their native structures.Action of ONOO-,synthesized in the authors' laboratory by a rapid quenched flow process,on structural changes of commercially available RNA was studied by ultraviolet (UV),fluorescence,and agarose gel electrophoresis.Compared to native RNA,the ONOO--modified RNA showed hyperchromicity at 260 nm.Furthermore,the ethidium bromide (EtBr) assisted emission intensities of ONOO--modified RNA samples were found to be lower than the emission intensity of native RNA-EtBr complex.Agarose gel electrophoresis of ONOO--modified RNA showed a gradual decrease in band intensities compared to native RNA,an observation clearly due to the poor intercalation of EtBr with ONOO--modified RNA.Native and ONOO--modified RNA samples were used as an antigen to detect autoantibodies in sera of patients with clinically defined breast cancer.Both direct binding and inhibition enzyme-linked immunosorbent assay (ELISA) confirmed the prevalence of native and 0.8 mmol/L ONOO--modified RNA specific autoantibodies in breast cancer patients.Moreover,the progressive retardation in the mobility of immune complexes formed with native or 0.8 mmol/L ONOO--modified RNA and affinity purified immunoglobulin G (IgG) from sera of breast cancer patients supports the findings of the direct binding and inhibition ELISAs.The peroxynitrite treatment to RNA at a higher concentration appears to have damaged or destroyed the typical epitopes on RNA and thus there was a sharp decrease in autoantibodies binding to 1.4 mmol/L ONOO--modified RNA.It may be interpreted that cellular nitrosative stress can modify and confer immunogenicity on RNA molecules.Higher concentrations of nitrogen reactive species can be detrimental to RNA.However,the emergence of

  12. Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy.

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    Yun Jung Oh

    Full Text Available The data were presented in abstract form at the 45(th meeting of the American Society of Nephrology, October 30-November 04 2012, San Diego, CA, USA. Circulating autoantibodies against M-type phospholipase A2 receptor (PLA2R are important pathogenic antibodies of idiopathic membranous nephropathy (MN in adults. However, previous studies on the clinical impact of anti-PLA2R antibodies demonstrated several limitations, including insufficient numbers of study subjects and different time points and methods for anti-PLA2R antibody measurement. To verify the clinical significance of anti-PLA2R antibodies in Korean patients with MN, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 100 patients with idiopathic MN who had not yet received immunosuppressive treatment. We detected anti-PLA2R antibody in 69 patients, and we observed that autoantibody reactivity reflected the severity of disease activity. Proteinuria and hypoalbuminemia were more severe in patients with anti-PLA2R than in those without the autoantibodies (2.95 g/g vs. 6.85 g/g, P = 0.003; 3.1 g/dL vs. 2.5 g/dL, P = 0.004, respectively. Additionally, the clinical severities worsened proportionally as the levels of anti-PLA2R antibodies increased (P = 0.015 and P for trend <0.001 for proteinuria and hypoalbuminemia, respectively. However, neither the levels nor the presence or absence of anti-PLA2R antibody showed a significant correlation with clinical outcomes, such as remission rate and time to remission. In conclusion, we observed that anti-PLA2R antibodies are highly prevalent in Korean patients with idiopathic MN and that they reflect the clinical disease activity before the administration of immunosuppressive treatment. However, the levels of anti-PLA2R antibody at the time of kidney biopsy may not predict the clinical outcomes in current clinical practice.

  13. Relationship between the autoantibody and expression of β3-adrenoceptor in lung and heart.

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    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.

  14. Plasma Autoantibodies against Heat Shock Protein 70, Enolase 1 and Ribonuclease/Angiogenin Inhibitor 1 as Potential Biomarkers for Cholangiocarcinoma

    Science.gov (United States)

    Rucksaken, Rucksak; Pairojkul, Chawalit; Pinlaor, Porntip; Khuntikeo, Narong; Roytrakul, Sittiruk; Selmi, Carlo; Pinlaor, Somchai

    2014-01-01

    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. PMID:25058392

  15. 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.

  16. 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.

  17. 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.

  18. Early pulmonary involvement of anti-CADM-140 autoantibody-positive rapidly progressive interstitial lung disease preceding typical cutaneous symptoms.

    Science.gov (United States)

    Tamai, Koji; Tachikawa, Ryo; Otsuka, Kyoko; Ueda, Hiroyuki; Hosono, Yuji; Tomii, Keisuke

    2014-01-01

    We herein report a patient with clinically amyopathic dermatomyositis (CADM) who developed anti-CADM-140 autoantibody in association with rapidly progressive interstitial lung disease (RP-ILD). Chest high-resolution computed tomography (HRCT) revealed early pulmonary involvement preceding typical cutaneous lesions. Primary lesions of patchy peribronchial opacity developed ground-glass opacity and consolidation with architectural distortion and traction bronchiectasis. The possibility of anti-CADM-140 autoantibody-associated RP-ILD should be considered when patchy peribronchial opacity of an unknown cause is visible on chest HRCT.

  19. 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...

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

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    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

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

    Directory of Open Access Journals (Sweden)

    Chan Koon H

    2010-09-01

    Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

  2. Neuropsychiatric autoimmune encephalitis without VGKC-complex, NMDAR, and GAD autoantibodies: case report and literature review.

    Science.gov (United States)

    Najjar, Souhel; Pearlman, Daniel; Devinsky, Orrin; Najjar, Amanda; Nadkarni, Siddhartha; Butler, Tracy; Zagzag, David

    2013-03-01

    We report a patient with a seronegative autoimmune panencephalitis, adding a subtype to the emerging spectrum of seronegative autoimmune encephalitis, and we review the sparse literature on isolated psychiatric presentations of autoimmune encephalitis. (A PubMed search for "seronegative autoimmune encephalitis," "nonvasculitic autoimmune inflammatory meningoencephalitis," and related terms revealed VGKC)-complex, N-methyl-D-aspartate receptor (NMDAR), and glutamic acid decarboxylase (GAD) autoantibodies. We excluded genetic, metabolic, paraneoplastic, degenerative, and infectious etiologies. The patient's symptoms remitted fully with immune therapy, but recurred in association with widespread bihemispheric brain lesions. Brain biopsy revealed mild nonvasculitic inflammation and prominent vascular hyalinization. Immune therapy with plasma exchanges cleared the MRI abnormalities but, 10 years after onset, the patient still suffers neuropsychiatric sequelae. We conclude that autoimmune panencephalitis seronegative for VGKC-complex, NMDAR, and GAD autoantibodies is a subtype of autoimmune encephalitis that can present with pure neuropsychiatric features and a normal brain MRI. Immunologic mechanisms may account for psychiatric symptoms in a subset of patients now diagnosed with classical psychotic disorders. Delay in starting immune therapy can lead to permanent neuropsychiatric sequelae. We propose a standardized classification system for the autoimmune encephalitides, integrating earlier pathology-oriented terms with more recently defined serologic and clinical phenotypes.

  3. Dialectics and Implications of Natural Neurotropic Autoantibodies in Neurological Disease and Rehabilitation

    Directory of Open Access Journals (Sweden)

    A. B. Poletaev

    2004-01-01

    Full Text Available The role of natural idiotypic (Id-Abs and anti-idiotypic (AId-Abs autoantibodies against neuro-antigens observed in different neurological disorders is not fully understood. In particular, limited experimental evidence has been provided concerning the qualitative and quantitative serological response after acute injuries of the central nervous system or during chronic mental diseases. In this study, we analyzed the specific Id-Abs and AId-Abs serological reactivities against 4 neuro-antigens in a large population of patients with ischemic stroke, schizophrenia, as well as healthy individuals. Patients with ischemic stroke were tested at different time points following the acute stroke episode and a correlation was attempted between autoantibodies response and different patterns of functional recovery. Results showed variable and detectable Id-Abs and AId-Abs in different proportions of all three populations of subjects. Among patients with different functional recovery after ischemic stroke, a difference in time-related trends of Id-Abs and AId-Abs was encountered. Our observations suggest that changes in the production of natural neurotropic Abs may engender a positive homeostatic, beside a possible pathogenic effect, in specific neurological disorders.

  4. Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury.

    Science.gov (United States)

    Hayes, K C; Hull, T C L; Delaney, G A; Potter, P J; Sequeira, K A J; Campbell, K; Popovich, P G

    2002-06-01

    This study characterized the proinflammatory cytokines, interleukin-2 (IL-2) and tumor necrosis factor alpha (TNFalpha), the antiinflammatory cytokines, IL-4 and IL-10, autoantibodies specific for GM1 ganglioside (anti-GM1), IgG and IgM, and myelin-associated glycoprotein (anti-MAG), in the sera of infection-free, chronic (>12 months), traumatically injured SCI patients (n = 24). Healthy able-bodied subjects (n = 26) served as controls. The proinflammatory cytokines and anti-GM1 antibodies were of particular interest as they have been implicated in an autoimmune "channelopathy" component to central and peripheral conduction deficits in various chronic neuroinflammatory diseases. Antibody and cytokine titers were established using enzyme-linked immunosorbent assays (ELISA). The mean anti-GM(1) (IgM) titer value for the SCI group was significantly higher (p proinflammatory cytokines relative to control values. These results provide preliminary support for the hypothesis that chronic immunological activation in the periphery occurs in a subpopulation of chronic SCI patients. It remains to be established whether elevated serum titers of proinflammatory cytokines and autoantibodies against GM1 are beneficial to the patients or whether they are surrogate markers of a channelopathy that compounds the neurological impairment associated with traumatic axonopathy or myelinopathy.

  5. A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors

    Science.gov (United States)

    Chen, Zeming; Patel, Jaymin M.; Noble, Philip W.; Garcia, Cesar; Hong, Zhangyong; Hansen, James E.; Zhou, Jiangbing

    2016-01-01

    Strategies to target nanoparticles to tumors that rely on surface modification with ligands that bind molecules overexpressed on cancer cells or the tumor neovasculature suffer from a major limitation: with delivery of toxic agents the amount of molecules available for targeting decreases with time; consequently, the efficiency of nanoparticle delivery is reduced. To overcome this limitation, here we propose an autocatalytic tumor-targeting mechanism based on targeting extracellular DNA (exDNA). exDNA is enriched in the tumor microenviroment and increases with treatment with cytotoxic agents, such as doxorubicin (DOX), due to release of DNA by dying tumor cells. We tested this approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface-conjugated with fragments of 3E10 (3E10EN), a lupus anti-DNA autoantibody. We demonstrated that 3E10EN-conjugated nanoparticles bound to DNA and preferentially localized to tumors in vivo. The efficiency of tumor localization of 3E10EN-conjugated, DOX-loaded nanoparticles increased with time and subsequent treatments, demonstrating an autocatalytic effect. 3E10EN-conjugated DOX-loaded nanoparticles exhibited a significant anti-tumor effect that was superior to all controls. This work demonstrates the promise of autocatalytic drug delivery mechanisms and establishes proof of concept for a new anti-DNA autoantibody-based approach for enhancing delivery of nanoparticles to tumors. PMID:27494868

  6. Autoantibodies in adult patients with idiopathic inflammatory myopathies in Buenos Aires.

    Science.gov (United States)

    Gómez, Graciela N; Gargiulo, María De Los Ángeles; Pérez, Nicolás; Collado, María Victoria; Suárez, Lorena V; Khoury, Marina; Sarano, Judith F

    2016-01-01

    The idiopathic inflammatory myopathies(IIM) are a heterogeneous group of diseases of the skeletal muscle. On the basis of clinical, serologic and histological differences, they are classified in dermatomyositis (DM), polymyositis (PM), inclusion body myositis and immunomediated necrotizing myopathy. Autoantibodies directed against nuclear and cytoplasmic antigens are present with variable frequencies among studies. Myositis-specific antibodies (MSAs) are useful in IIM because they contribute to the diagnosis, help to identify different clinical subsets, and have prognostic value. This study aimed to explore the frequency of autoantibodies, especially MSAs, and their relationship with clinical features in adult patients with DM, PM and overlap syndrome. Medical records were reviewed. Myositis-associated antibodies (non-specific) and MSAs (anti Jo-1, PL-7, PL-12, Mi-2 and SRP) were measured using commercial kits. Twelve patients had MSAs, an overall frequency similar to those of international series, but PL-12 and Mi-2 were more frequent than Jo-1, which is the most frequently observed elsewhere. All five patients with Mi-2 had classical DM with a favorable response to treatment. Interstitial pneumonia (n: 4) and/or treatment-refractory disease (n: 3) were found in the presence of anti-PL-12, alone or associated with anti-SRP and/or Jo-1. In conclusion, the coexistence of AEM, a rare finding, was found in three patients. The presence of MSAs aided to the diagnosis of IIM, in particular in those patients without available or conclusive biopsy results.

  7. 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.

  8. 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.

  9. Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis

    Science.gov (United States)

    Caster, Dawn J.; Korte, Erik A.; Merchant, Michael L.; Klein, Jon B.; Wilkey, Daniel W.; Rovin, Brad H.; Birmingham, Dan J.; Harley, John B.; Cobb, Beth L.; Namjou, Bahram; McLeish, Kenneth R.; Powell, David W.

    2015-01-01

    PURPOSE Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. EXPERIMENTAL DESIGN Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. RESULTS LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36-50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. CONCLUSION AND CLINICAL RELEVANCE Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. PMID:25824007

  10. Non-specific binding in solid phase immunoassays for autoantibodies correlates with inflammation markers.

    Science.gov (United States)

    Güven, Esin; Duus, Karen; Lydolph, Magnus Christian; Jørgensen, Charlotte Sværke; Laursen, Inga; Houen, Gunnar

    2014-01-31

    Enzyme-linked immunosorbent assay (ELISA) is a validated and sensitive method for detection of human autoantibodies, but may have problems with specificity. Non-specific binding is a well-known problem often observed in tests for autoantibodies, when sera are incubated on plastic surfaces, e.g. an ELISA plate. To understand the mechanisms underlying non-specific immunoglobulin deposition, we here analyse the phenomenon in detail and we propose means of reducing false positive test results caused by non-specific binding. The level of non-specific binding, in sera with suspected autoreactivity, was analysed in non-coated and autoantigen-coated ELISA wells and 4-32% of sera showed a high level of non-specific binding depending on the assay conditions and serum properties. Non-specifically binding sera were found to contain increased concentrations of IgG and other inflammatory mediators. Moreover, non-specific binding could be induced in serum by increasing the concentration of IgG and incubating the serum at 40 °C. This suggests that non-specific binding immunoglobulins can be formed during inflammation with high immunoglobulin levels and elevated temperature. We show that the level of non-specific binding correlates with the IgG concentration and therefore propose that non-specific binding may be interpreted as an informative finding indicative of elevated IgG and inflammation.

  11. Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy.

    Science.gov (United States)

    Zandian, Arash; Forsström, Björn; Häggmark-Månberg, Anna; Schwenk, Jochen M; Uhlén, Mathias; Nilsson, Peter; Ayoglu, Burcu

    2017-02-09

    The underlying molecular mechanisms of autoimmune diseases are poorly understood. To unravel the autoimmune processes across diseases, comprehensive and unbiased analyses of proteins targets recognized by the adaptive immune system are needed. Here we present an approach starting from high-density peptide arrays to characterize autoantibody repertoires and to identify new autoantigens. A set of ten plasma and serum samples from subjects with multiple sclerosis, narcolepsy, and without any disease diagnosis were profiled on a peptide array representing the whole proteome, hosting 2.2 million 12-mer peptides with a six amino acid lateral shift. On the basis of the IgG reactivities found on these whole-proteome peptide microarrays, a set of 23 samples was then studied on a targeted array with 174 000 12-mer peptides of single amino acid lateral shift. Finally, verification of IgG reactivities was conducted with a larger sample set (n = 448) using the bead-based peptide microarrays. The presented workflow employed three different peptide microarray formats to discover and resolve the epitopes of human autoantibodies and revealed two potentially new autoantigens: MAP3K7 in multiple sclerosis and NRXN1 in narcolepsy. The presented strategy provides insights into antibody repertoire reactivity at a peptide level and may accelerate the discovery and validation of autoantigens in human diseases.

  12. 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.

  13. Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.

    Science.gov (United States)

    Tsao, B P; Ebling, F M; Roman, C; Panosian-Sahakian, N; Calame, K; Hahn, B H

    1990-02-01

    We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.

  14. 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.

  15. An impedimetric immunosensor for the detection of autoantibodies directed against gliadins.

    Science.gov (United States)

    Balkenhohl, T; Lisdat, F

    2007-04-01

    An immunosensor has been developed for the detection of autoantibodies directed against wheat gliadin, a protein fraction of cereal gluten which is involved in celiac disease. The immunosensor is based on the immobilization of gliadins onto gold electrodes covered with a polyelectrolyte layer of poly(4-styrenesulfonic acid sodium salt). The immobilization was monitored by quartz crystal microbalance (QCM) analysis. The antigen-antibody interaction signal was amplified by an incubation step with peroxidase-labeled immunoglobulins and subsequent peroxidase-catalyzed oxidation of 3-amino-9-ethylcarbazole (AEC). Changes in the insulating properties of the electrode layer were measured by electrochemical impedance spectroscopy (EIS) in the presence of ferri/ferro-cyanide. Impedance spectra could be fitted to a Randles equivalent circuit with high accuracy. Exposing the sensor electrodes to various antigliadin antibody concentrations resulted in proportional changes in the charge transfer resistance. A calibration graph for the detection of antigliadin antibodies was established for antibody concentrations between 10(-8) and 10(-6) M. Finally, the sensor was used for the determination of antigliadin autoantibodies of the IgG and IgA type in several human sera.

  16. 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.

  17. Autoantibody against Cardiac β1-Adrenoceptor Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Yan GAO; Hui-Rong LIU; Rong-Rui ZHAO; Jian-Ming ZHI

    2006-01-01

    To clarify whether apoptosis is involved in the injury processes induced by autoantibody against cardiac β1-adrenoceptor, we investigated the biological and apoptotic effects of antibodies on cultured neonatal rat cardiomyocytes. Wistar rats were immunized with peptides corresponding to the second extracellular loop of the β1-adrenoceptor to induce the production of anti-β1-adrenoceptor antibodies in the sera.Immunoglobulin (Ig) G in the sera was detected using synthetic antigen enzyme-linked immunosorbent assay and purified using the diethylaminoethyl cellulose ion exchange technique. Apoptosis of cardiomyocytes was evaluated using agarose gel electrophoresis and flow cytometry. Our results showed that the positive serum IgG greatly increased the beating rates of cardiomyocytes and showed an "agonist-like" activity. Furthermore, positive serum IgG induced cardiomyocyte apoptosis after treatment with β1adrenoceptor overstimulation for 48 h. The effects of monoclonal antibody against β1-adrenoceptor were also found to be similar to those of positive serum IgG. It was suggested that the autoantibody could induce cardiomyocyte apoptosis by excessive stimulation of β1-adrenoceptor.

  18. Idiopathic Inflammatory Myopathies; Association with Overlap Myositis and Syndromes: Classification, Clinical Characteristics, and Associated Autoantibodies

    Directory of Open Access Journals (Sweden)

    Pari Basharat

    2016-07-01

    Full Text Available Idiopathic inflammatory myopathies (IIM are traditionally identified as a group of disorders that target skeletal muscle due to autoimmune dysfunction. The IIM can be divided into subtypes based on certain clinical characteristics, and several classification schemes have been proposed. The predominant diagnostic criteria for IIM is the Bohan and Peter criteria, which subdivides IIM into primary polymyositis (PM, primary dermatomyositis (DM, myositis with another connective tissue disease, and myositis associated with cancer. However, this measure has been criticised for several reasons including lack of specific criteria to help distinguish between muscle biopsy findings of PM, DM, and immune-mediated necrotising myopathy, as well as the lack of identification of cases of overlap myositis (OM. Because of this issue, other classification criteria for IIM have been proposed, which include utilising myositis-associated antibodies and myositis-specific antibodies, as well as overlap features such as Raynaud’s phenomenon, polyarthritis, oesophageal abnormalities, interstitial lung disease, small bowel abnormalities such as hypomotility and malabsorption, and renal crises, amongst others. Indeed, the identification of autoantibodies associated with certain clinical phenotypes of myositis, in particular connective tissue disease-myositis overlap, has further helped divide IIM into distinct clinical subsets, which include OM and overlap syndromes (OS. This paper reviews the concepts of OM and OS as they pertain to IIM, including definitions in the literature, clinical characteristics, and overlap autoantibodies.

  19. Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus.

    Science.gov (United States)

    Vaz, João Luiz Pereira; Andrade, Carlos Augusto Ferreira; Pereira, Alessandra Cardoso; Martins, Maria de Fátima M; Levy, Roger Abramino

    2013-08-01

    The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.

  20. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.

    Science.gov (United States)

    Beck, Laurence H; Fervenza, Fernando C; Beck, David M; Bonegio, Ramon G B; Malik, Fahim A; Erickson, Stephen B; Cosio, Fernando G; Cattran, Daniel C; Salant, David J

    2011-08-01

    Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

  1. Auto-anticorpos na Esclerose Sistêmica (ES Autoantibody in the Systemic Sclerosis (SS

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    Luís Eduardo Coelho Andrade

    2004-06-01

    Full Text Available A esclerose sistêmica (ES é uma enfermidade inflamatória crônica idiopática, cujo principal indício de vínculo com a auto-imunidade é a presença de auto-anticorpos na maior parte dos pacientes. Pelo teste de imunofluorescência indireta em células HEp-2, observa-se reatividade predominantemente contra o nucléolo e o núcleo, sendo que títulos de anticorpos antinucléolo acima de 1/640 são fortemente sugestivos de ES. Alguns desses auto-anticorpos apresentam alta especificidade para a ES, sendo considerados marcadores diagnósticos dessa enfermidade. São exemplos os anticorpos anti-Scl-70, antifibrilarina e anti-RNA polimerase I. Outros apresentam interessantes associações com manifestações específicas da ES, como os anticorpos anticentrômero, associados às formas limitadas, os anticorpos anti-RNA polimerase III, associados ao extenso comprometimento da pele, e os anticorpos anti-To/Th, associados às formas limitadas com propensão ao desenvolvimento de hipertensão pulmonar. Algumas dessas associações estão bem estabelecidas em diversos estudos, de diferentes grupos de pesquisadores. Outras, entretanto, devem ser vistas com cautela, pois a exigüidade de casos disponíveis para estudo pode ensejar conclusões preliminares e não acuradas. A detecção de anticorpos anticentrômero por técnica de IFI e anti-Scl-70 por imunodifusão dupla ou por ELISA está disponível nos principais laboratórios clínicos capacitados na área de auto-imunidade. O mesmo não se aplica para a maior parte dos demais auto-anticorpos associados à ES. Espera-se que, com a implementação rotineira de técnicas para detecção desses outros auto-anticorpos, o real significado clínico dos mesmos venha a ser melhor conhecido.Systemic Sclerosis (SS is a chronic idiopathic inflammatory disease whose main hint towards autoimmunity is given by the presence of high serum levels of autoantibodies in the majority of the patients. In indirect

  2. 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.;

    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...

  3. Familial occurrence of autoimmune diseases and autoantibodies in a Caucasian population of patients with systemic lupus erythematosus

    NARCIS (Netherlands)

    Corporaal, S.; Bijl, Marc; Kallenberg, Cees

    2002-01-01

    To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation: as

  4. Small-cell lung cancer-associated autoantibodies: potential applications to cancer diagnosis, early detection, and therapy

    Directory of Open Access Journals (Sweden)

    Laird-Offringa Ite A

    2011-03-01

    Full Text Available Abstract Small-cell lung cancer (SCLC is the most aggressive lung cancer subtype and lacks effective early detection methods and therapies. A number of rare paraneoplastic neurologic autoimmune diseases are strongly associated with SCLC. Most patients with such paraneoplastic syndromes harbor high titers of antibodies against neuronal proteins that are abnormally expressed in SCLC tumors. These autoantibodies may cross-react with the nervous system, possibly contributing to autoimmune disease development. Importantly, similar antibodies are present in many SCLC patients without autoimmune disease, albeit at lower titers. The timing of autoantibody development relative to cancer and the nature of the immune trigger remain to be elucidated. Here we review what is currently known about SCLC-associated autoantibodies, and describe a recently developed mouse model system of SCLC that appears to lend itself well to the study of the SCLC-associated immune response. We also discuss potential clinical applications for these autoantibodies, such as SCLC diagnosis, early detection, and therapy.

  5. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker.

    NARCIS (Netherlands)

    Nijenhuis, S.; Zendman, A.J.W.; Vossenaar, E.R.; Pruijn, G.J.M.; Venrooij, W.J.W. van

    2004-01-01

    Rheumatoid arthritis (RA) is a common, systemic autoimmune disease of which the exact etiology is not known. In the past 10 years, substantial progress has been made in the identification of the antigens specifically recognized by the autoantibodies of RA patients. A central factor in this respect i

  6. Plasma IgG autoantibody against actin-related protein 3 in liver fluke Opisthorchis viverrini infection.

    Science.gov (United States)

    Rucksaken, R; Haonon, O; Pinlaor, P; Pairojkul, C; Roytrakul, S; Yongvanit, P; Selmi, C; Pinlaor, S

    2015-07-01

    Opisthorchiasis secondary to Opisthorchis viverrini infection leads to cholangiocellular carcinoma through chronic inflammation of the bile ducts and possibly inducing autoimmunity. It was hypothesized that plasma autoantibodies directed against self-proteins are biomarkers for opisthorchiasis. Plasma from patients with opisthorchiasis was tested using proteins derived from immortalized cholangiocyte cell lines, and spots reacting with plasma were excised and subjected to LC-MS/MS. Seven protein spots were recognized by IgG autoantibodies, and the highest matching scored protein was actin-related protein 3 (ARP3). The antibody against ARP3 was tested in plasma from 55 O. viverrini-infected patients, 24 patients with others endemic parasitic infections and 17 healthy controls using Western blot and ELISA. Immunoreactivity against recombinant ARP3 was significantly more prevalent in opisthorchiasis compared to healthy controls at Western blotting and ELISA (P < 0.05). Plasma ARP3 autoantibody titres were also higher in opisthorchiasis compared to healthy individuals (P < 0.01) and other parasitic infections including Strongyloides stercoralis (P < 0.001), echinostome (P < 0.05), hookworms (P < 0.001) and Taenia spp. (P < 0.05). It was further characterized in that the ARP3 autoantibody titre had a sensitivity of 78.18% and specificity of 100% for opisthorchiasis. In conclusion, it may be suggested that plasma anti-ARP3 might represent a new diagnostic antibody for opisthorchiasis.

  7. Complement Activation Is Involved in Renal Damage in Human Antineutrophil Cytoplasmic Autoantibody Associated Pauci-Immune Vasculitis

    NARCIS (Netherlands)

    Xing, Guang-qun; Chen, Min; Liu, Gang; Heeringa, Peter; Zhang, Jun-jun; Zheng, Xin; Jie, E.; Kallenberg, Cees G. M.; Zhao, Ming-hui

    2009-01-01

    This study was to investigate the evidence for complement activation in renal biopsy specimens of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune vasculitis. Renal biopsy specimens from seven patients with MPO-ANCA positive pauci-immune necr

  8. Role of sodium silicate in induction of scleroderma-related autoantibodies in brown Norway rats through oral and subcutaneous administration.

    Science.gov (United States)

    Al-Mogairen, Sultan M

    2011-05-01

    Silica hazard is a growing occupational problem and has been reported to be associated with scleroderma via case reports and occupational studies. The aim of this study is to demonstrate whether oral or subcutaneous silicate exposure can induce an autoimmunity and scleroderma susceptibility in immunosensitive rats. Sodium silicate in a dose of 3 mg in 0.2 ml NS was administered through oral and subcutaneous routes to 20 brown Norway rats. Autoantibodies including ANA, anti-RNP, anti-SCL70 and anti-centromere were measured and compared with pre- and post-challenge serum samples. Serum ANA and anti-RNP were high in significant number of rats (P < 0.05) of only the subcutaneous silicate group. There is an increase in the number of positive readings of autoantibodies at 14th week in comparison with the number of positive readings of autoantibodies at 7th week but P values were not significant. It may be concluded that silicate might induce autoimmunity and scleroderma and it seems to be that the longer the duration of exposure the greater the risk. This is probably the first experimental animal study demonstrating the induction of scleroderma-related autoantibodies after challenge with silicate.

  9. 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

    2016-01-01

    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...

  10. The interleukin-20 receptor axis in early rheumatoid arthritis: novel links between disease-associated autoantibodies and radiographic progression

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Greisen, Stinne Ravn; Nielsen, Morten Aagaard

    2016-01-01

    by osteoclast precursors and in multinucleated osteoclasts. IL-20 and IL-24 increased the secretion of monocyte chemoattractant protein 1 by these cells. CONCLUSIONS: This study suggests that IL-20 and IL-24 link RA-associated autoantibodies with radiographic progression via the IL-22R1. Modulation of this axis...

  11. 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

  12. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.

    NARCIS (Netherlands)

    Gaalen, van FA; Linn-Rasker, SP; Venrooij, W.J.; Jong, B.A.; Breedveld, F.C.; Verweij, C.L.; Toes, RE; Huizinga, T.W.

    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

  13. 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

  14. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette;

    2006-01-01

    The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients...

  15. Rheumatoid arthritis-associated autoantibodies in non-rheumatoid arthritis patients with mucosal inflammation : a case-control study

    NARCIS (Netherlands)

    Janssen, Koen M. J.; de Smit, Menke J.; Brouwer, Elisabeth; de Kok, Fenne A. C.; Kraan, Jan; Altenburg, Josje; Verheul, Marije K.; Trouw, Leendert A.; van Winkelhoff, Arie Jan; Vissink, Arjan; Westra, Johanna

    2015-01-01

    Introduction: Rheumatoid arthritis-associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of t

  16. 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

  17. Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F.

    Science.gov (United States)

    Fritzler, Marvin J; Rattner, Jerome B; Luft, LeeAnne M; Edworthy, Steven M; Casiano, Carlos A; Peebles, Carol; Mahler, Michael

    2011-02-01

    Autoantibodies to the centromere proteins (CENP), which are major constituents of the primary constriction of metaphase chromosomes, were first described in 1980. In those seminal publications and 30 years of research that have followed, a number of CENP have been identified as autoantibody targets in human diseases. Historically, autoantibodies directed to CENP-A, -B and -C have been considered relatively specific biomarkers for limited cutaneous systemic sclerosis (lcSSc) or the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. These autoantibodies, found in up to 40% of SSc sera, can be identified by indirect immunofluorescence (IIF) on a variety of tissue culture cell lines as a discrete speckled staining pattern of both interphase nuclei and metaphase chromatin. Early in the investigation of anti-CENP, it became apparent that some autoantibodies had a similar IIF pattern wherein as cells entered into the cell cycle, speckled staining of the metaphase chromatin could be observed but, unlike conventional CENP staining, interphase nuclei were not stained. Subsequent studies identified one of the targets of these autoantibodies to be CENP-F, a kinesin binding protein essential for completion of the cell cycle. Early clinical studies found that, unlike antibodies to the earlier described CENP, lcSSc rarely expressed anti-CENP-F and approximately 50% of these patients had a malignancy. This review provides a historical perspective of CENP autoantibodies and focuses on an update of the information on CENP-F and their clinical associations.

  18. Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM1 in hepatitis C seropositive subjects on Crete, Greece

    Directory of Open Access Journals (Sweden)

    Pappas Georgios

    2001-06-01

    Full Text Available Abstract Background Hepatitis C is a serious problem on the Greek island of Crete, where a high prevalence of antibodies against hepatitis C (anti-HCV has recently been reported. This article reports the findings of a study carried out in Crete, which investigated the prevalence of serum autoantibodies in patients with chronic hepatitis C. Patients and Methods One hundred and forty two patients (59 men and 83 women, who were found anti-HCV seropositive in two hospitals and two Primary Health Care Centres in Crete, were eligible. Sixty healthy blood donors (46 men, 14 women, which were negative to anti-HCV, were used as the control group. They were randomly selected from those attending Rethymnon Hospital. Autoantibodies were identified using the indirect immunofluorescence (IFL technique on human epithelial cells from larynx cancer (HEp-2 cells, rat liver-kidney-stomach substrate (CT3 and Chrithidia Luciliae (CL. Results Serum autoantibodies were detected in 104 HCV patients, yielding an overall prevalence of 73.2%. The most frequent autoantibodies were antinuclear antibodies (ANA, positive in 72 patients (50.7%. Anti-smooth muscle antibodies (ASMA were detected in 33 patients (23.2%. Only one patient was positive for LKM1 autoantibodies. No autoantibodies were found in 38 patients (26.7%. Autoantibodies were also found in 5 out of the 60 examined healthy blood donors (8.3%. Conclusions Autoantibodies, mainly ANA and ASMA are very common in HCV seropositive patients from Crete. By contrast LKM1 autoantibodies are exceptionally rare in these patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Victoria, E.J.; Pierce, S.W.; Branks, M.J.; Masouredis, S.P. (Univ. of California, San Diego (USA))

    1990-01-01

    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.

  20. Autoantibodies as Biomarkers for the Prediction of Neuropsychiatric Events in Systemic Lupus Erythematosus

    Science.gov (United States)

    Hanly, J G; Urowitz, M B; Su, L; Bae, S-C; Gordon, C; Sanchez-Guerrero, J; Clarke, A; Bernatsky, S; Vasudevan, A; Isenberg, D; Rahman, A; Wallace, D J; Fortin, P R; Gladman, D; Dooley, M A; Bruce, I; Steinsson, K; Khamashta, M; Manzi, S; Ramsey-Goldman, R; Sturfelt, G; Nived, O; van Vollenhoven, R; Ramos-Casals, M; Aranow, C; Mackay, M; Kalunian, K; Alarcón, G S; Fessler, B J; Ruiz-Irastorza, G; Petri, M; Lim, S; Kamen, D; Peschken, C; Farewell, V; Thompson, K; Theriault, C; Merrill, J T

    2015-01-01

    Objective Neuropsychiatric (NP) events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. We examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrollment predicted subsequent NP events. Methods Patients with recent SLE diagnosis were assessed prospectively for up to 10 years for NP events using ACR case definitions. Decision rules of graded stringency determined whether NP events were attributable to SLE. Associations between the first NP event and baseline autoantibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrollment was 5.4±4.2 months, followup was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed ≥1 NP event (total 917 events). NP events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrollment 21.9% of patients had lupus anticoagulant, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. Lupus anticoagulant at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (Hazard ratio, HR 2.54 (95% CI: 1.08–5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR: 3.92 (95% CI:1.23–12.5); p=0.02). Other autoantibodies did not predict NP events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, lupus anticoagulant and anti-ribosomal P antibodies are associated with an increased future risk for intracranial thrombosis and lupus psychosis respectively PMID:21893582

  1. Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome.

    Science.gov (United States)

    Lawind, Mohamed F; Alyasky, Ahmed; Elwan, Nahed M; Mourad, Heba; Al-Bendary, Amal

    2004-01-01

    Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine

  2. Value of autoantibody detection for illness assessment in systemic lupus erythematosus patients with refractory thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    Xiao-Liang Wu

    2016-01-01

    Objective:To analyze the value of autoantibody detection for illness assessment in systemic lupus erythematosus patients with refractory thrombocytopenia.Methods:A total of 60 cases of systemic lupus erythematosus (SLE) with refractory thrombocytopenia were the observation group A, 58 cases of patients with SLE alone were the observation group B, and 66 cases of healthy people who received physical examination were control group. Peripheral circulating blood was drawn from research subjects to detect the levels of autoantibody, illness-related factors, Th17, Th1 and Th2 cytokines, complements, and so on, and then the correlation between specific antibody positive rate and disease severity in SLE patients with refractory thrombocytopenia was further analyzed.Results:Anti-RNP antibody, anti-Sm antibody, anti-Scl-70 antibody, anti-AnuA antibody, anti-His antibody and anti-ds-DNA antibody positive rates of observation group A were higher than those of observation group B and control group (P<0.05); sICAM-1, PTM, sCD30L and MCP-1 values of observation group A were higher than those of observation group B and control group (P<0.05); serum IL-17, IL-23, IFN-γ, TNF-α, IL-4, IL-5 and IL-6 values of observation group A were higher than those of observation group B and control group (P<0.05); serum C1qAg, C3, C4 and CFH values of observation group A were lower than those of observation group B and control group while C1qAb value was higher than that of observation group B and control group (P<0.05); anti-Sm antibody and anti-ds-DNA antibody positive rates of SLE patients were positively correlated with serum sICAM-1, PTM, sCD30L, MCP-1, IL-17, IL-23, IFN-γ, TNF- , IL-4, IL-5, IL-6 and C1qAb values, and negatively correlated with C1qAg, C3, C4 and CFH values (P<0.05). Conclusions:Specific autoantibody positive rates are high in systemic lupus erythematosus patients with refractory thrombocytopenia, have direct correlation with the disease severity and can be used as the

  3. Type 1 diabetes risk and autoantibody positivity in Sardinian migrants in the province of Pavia

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    Maria T Tenconi

    2009-01-01

    Full Text Available Background : Type 1 diabetes is an autoimmune disease. Genetics as well as environmental factors seem to play a role in the pathogenesis of type 1 diabetes. Aims : We sought to investigate the possible relationship between migration from Sardinia to a low incidence area of type 1 diabetes (Lombardy and the prevalence of autoantibody positivity. Methods : We enrolled 554 Sardinian immigrants and 226 of their offspring. All subjects underwent a complete anamnestic evaluation. Fasting blood glucose, HbA1c, GADA and IA-2 were measured in all study participants. Additionally, the presence of risk haplotypes (HLA-DR3 -DR4 and DQB1/0302 was determined. After a seven-year follow-up, high genetic risk and/or autoantibody positivity subjects were re-evaluated. Results : Among Sardinian immigrants, the prevalence of type 1 diabetes was 0.9%, while in the offspring group, the prevalence was 0.4%. After removing type 1 diabetic patients, the GADA prevalence was 2.4% in the immigrant group and 3.8% among their offspring. Among Sardinian immigrants, the IA-2 prevalence was 0.7%, while all offspring were IA-2 negative. After a seven-year follow-up, 85.7% of GADA-positive migrants had persistent GADA positivity. Two GADA-negative offspring subjects turned positive. None of the study participants developed diabetes during the follow-up. Conclusions : The present study showed a higher prevalence of GADA positivity within Sardinian immigrants at high genetic risk; GADA positivity may represent the first detectable phase of type 1 diabetes. After a seven-year follow-up, none of the high genetic/antibody risk group subjects developed type 1 diabetes. However, it seems reasonable to strictly control high-risk individuals in order to diagnose subclinical diabetes. (Tenconi MT, Devoti G, Rizzo M, Federico Roncarolo F, Bernasconi A, Lanati N, Calcaterra V, Songini M, Locatelli M, Gian F. Bottazzo Type 11 diabetes risk and autoantibody positivity in Sardinian migrants in

  4. Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris Affected with Hypoadrenocorticism (Addison's Disease.

    Directory of Open Access Journals (Sweden)

    Alisdair M Boag

    Full Text Available Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD or autoimmune polyendocrine syndrome (APS, circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH, CYP17A1 (17-hydroxylase; 17-OH, CYP11A1 (P450 side-chain cleavage enzyme; P450scc and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation. Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016. Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037. Significant associations with breed (p = 0.015 and DLA-type (DQA1*006:01 allele; p = 0.017 were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.

  5. Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease).

    Science.gov (United States)

    Boag, Alisdair M; Christie, Michael R; McLaughlin, Kerry A; Syme, Harriet M; Graham, Peter; Catchpole, Brian

    2015-01-01

    Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.

  6. [The effect of long-term exposure to low doses of endocrine disruptor ddt on serum levels of thyroid protein autoantigenes and antithyroid autoantibodies].

    Science.gov (United States)

    Yaglova, N V; Yaglov, V V

    2016-01-01

    Changes in secretion of thyroid autoantigenes and production of antithyroid autoantibodies after long-term exposure to low doses of DDT were studied. Changes in serum levels of antithyroid peroxidase antibodies and thyroid peroxidase, attributed to disruption of thyroxine production by DDT were found. Long-term exposure of rats to low doses of DDT revealed no specific impact on serum autoantibodies to all thyroid autoantigenes studied. The increase of the ratio of autoantibody/autoantigen for thyroid peroxidase and thyroglobulin was rather small and thus could not be considered as a significant symptom of thyroid autoimmunity.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    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...... but the former were more prevalent. The cerebrospinal fluid (CSF) leukocyte count and the number of anti-protelipid protein antibody-secreting cells in cerebrospinal fluid (CSF) correlated with disease activity in POSMS. Intrathecal IgG synthesis levels and the number of anti-myelin basic protein antibody......-secreting cells in CSF correlated with disease activity in CDMS. Our results support recent reports of pathogenetic heterogeneity and a pathogenetic role of the antibody response in MS...

  8. Advances in understanding newer autoantibodies and their role as biomarkers in systemic lupus erythematosus.

    Science.gov (United States)

    Fritzler, Marvin J

    2007-11-01

    Autoantibodies (AAs) were first associated with systemic lupus erythematosus (SLE) in the 1950s and since then > 155 have been described in SLE sera. Of these, only a few have achieved recognition as important biomarkers in the classification, diagnosis, prediction, prognosis and pathogenesis of the disease. Although some long-established AAs, such as anti-dsDNA, anti-Sm and anticardiolipin, have taken center stage in classification criteria and pathogenic studies, some of the newer and less understood AAs may have equally important disease relevance. This review will focus on evidence for: i) the importance of AAs as biomarkers for early disease; ii) a consideration that certain AAs should be added as serologic criteria for the classification and diagnosis of SLE and that present serologic criteria should be reevaluated; and iii) a role of AAs in the pathogenesis and prognosis of SLE.

  9. 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...

  10. Prolactin levels and autoantibodies in female patients with systemic lupus erythematosus.

    Science.gov (United States)

    Kozáková, D; Rovenský, J; Cebecauer, L; Bosák, V; Jahnová, E; Vigas, M

    2000-01-01

    We investigated the relationships between prolactin (PRL) levels and antibody occurrence in systemic lupus erythematosus (SLE). No significant association between PRL levels and the majority of the autoantibodies studied (anti-U1 RNP, anti-rRNP, anti-Sm, anti-dsDNA, anti-DNP, auto-LCA, anti-EACA) could be confirmed (P > 0.05), anti-Ro/SSA antibodies being an exception. Our results showed significantly increased frequencies of these antibodies in the group of female SLE patients with normal PRL levels (< 20 micrograms/L): anti Ro/SSA in 53% (P < 0.025, chi 2 = 5.80, RR = 4.0) and anti-Ro/SSA + anti-Ro/La in 60% (P < 0.05, chi 2 = 4.05) compared with female SLE patients with hyperprolactinemia.

  11. 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;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with immunoinflammatory diseases and cytokine-dependent tumours....

  12. Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diagnosis of rheumatic diseases.

    Science.gov (United States)

    Palazzi, Carlo; Buskila, Dan; D'Angelo, Salvatore; D'Amico, Emilio; Olivieri, Ignazio

    2012-07-01

    Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40-70% of patients suffering from this disorder develop at least one extra-hepatic disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and sicca syndrome) and must be differentiated from the primitive rheumatic diseases. In addition, HCV infection can also alter the laboratory tests. Several alterations of first line laboratory tests can be usually found in both chronic HCV infection and chronic inflammatory rheumatic disorders. In the present review we analyze the interference of HCV in tests more specifically used in rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA, anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection, the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA) should be made only when the detected symptoms or laboratory data are not inducible by HCV, otherwise only a diagnosis of "possible CTD" or "possible RA" should be considered.

  13. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis.

    Science.gov (United States)

    Petzold, A; Pittock, S; Lennon, V; Maggiore, C; Weinshenker, B G; Plant, G T

    2010-01-01

    The clinical course of immune mediated optic neuritis (ON) will depend on the specific underlying inflammatory disease. These disorders have traditionally been classified according to clinical and MRI findings. Aquaporin-4 (AQP4) autoantibodies (neuromyelitis optica-IgG (NMO-IgG)) may have diagnostic and prognostic value in patients who present with isolated ON. In this prospective study, NMO-IgG was evaluated in 114 patients with ON in the following contexts: neuromyelitis optica (NMO), multiple sclerosis (MSON), chronic relapsing inflammatory ON (CRION), relapsing isolated ON (RION) and single isolated ON (SION). The proportion seropositive was 56% for NMO (n = 9), 0% for MSON (n = 28) and 5% for the remaining diagnostic categories (CRION (n = 19), RION (n = 17) and SION (n = 41)). Testing for NMO-IgG in patients with recurrent or severe ON who lack convincing evidence of MS may identify patients who would benefit from immunosuppression rather than MS directed immunomodulatory therapies.

  14. Stiff person syndrome-associated autoantibodies to amphiphysin mediate reduced GABAergic inhibition.

    Science.gov (United States)

    Geis, Christian; Weishaupt, Andreas; Hallermann, Stefan; Grünewald, Benedikt; Wessig, Carsten; Wultsch, Thomas; Reif, Andreas; Byts, Nadiya; Beck, Marcus; Jablonka, Sibylle; Boettger, Michael K; Üçeyler, Nurcan; Fouquet, Wernher; Gerlach, Manfred; Meinck, Hans-Michael; Sirén, Anna-Leena; Sigrist, Stephan J; Toyka, Klaus V; Heckmann, Manfred; Sommer, Claudia

    2010-11-01

    Synaptic inhibition is a central factor in the fine tuning of neuronal activity in the central nervous system. Symptoms consistent with reduced inhibition such as stiffness, spasms and anxiety occur in paraneoplastic stiff person syndrome with autoantibodies against the intracellular synaptic protein amphiphysin. Here we show that intrathecal application of purified anti-amphiphysin immunoglobulin G antibodies induces stiff person syndrome-like symptoms in rats, including stiffness and muscle spasms. Using in vivo recordings of Hoffmann reflexes and dorsal root potentials, we identified reduced presynaptic GABAergic inhibition as an underlying mechanism. Anti-amphiphysin immunoglobulin G was internalized into neurons by an epitope-specific mechanism and colocalized in vivo with presynaptic vesicular proteins, as shown by stimulation emission depletion microscopy. Neurons from amphiphysin deficient mice that did not internalize the immunoglobulin provided additional evidence of the specificity in antibody uptake. GABAergic synapses appeared more vulnerable than glutamatergic synapses to defective endocytosis induced by anti-amphiphysin immunoglobulin G, as shown by increased clustering of the endocytic protein AP180 and by defective loading of FM 1-43, a styryl dye used to label cell membranes. Incubation of cultured neurons with anti-amphiphysin immunoglobulin G reduced basal and stimulated release of γ-aminobutyric acid substantially more than that of glutamate. By whole-cell patch-clamp analysis of GABAergic inhibitory transmission in hippocampus granule cells we showed a faster, activity-dependent decrease of the amplitude of evoked inhibitory postsynaptic currents in brain slices treated with antibodies against amphiphysin. We suggest that these findings may explain the pathophysiology of the core signs of stiff person syndrome at the molecular level and show that autoantibodies can alter the function of inhibitory synapses in vivo upon binding to an

  15. Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

    Science.gov (United States)

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L.; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10−8 M) and carbachol (10−9 M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression. PMID:23460876

  16. Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    María Gabriela Lombardi

    Full Text Available The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10(-8 M and carbachol (10(-9 M increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

  17. Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis.

    Science.gov (United States)

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10(-8) M) and carbachol (10(-9) M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

  18. Increased circulating β2-adrenergic receptor autoantibodies are associated with smoking-related emphysema

    Science.gov (United States)

    Hu, Jia-yi; Liu, Bei-bei; Du, Yi-peng; Zhang, Yuan; Zhang, Yi-wei; Zhang, You-yi; Xu, Ming; He, Bei

    2017-01-01

    Smoking is a dominant risk factor for chronic obstructive pulmonary disease (COPD) and emphysema, but not every smoker develops emphysema. Immune responses in smokers vary. Some autoantibodies have been shown to contribute to the development of emphysema in smokers. β2-adrenergic receptors (β2-ARs) are important targets in COPD therapy. β2-adrenergic receptor autoantibodies (β2-AAbs), which may directly affect β2-ARs, were shown to be increased in rats with passive-smoking-induced emphysema in our current preliminary studies. Using cigarette-smoke exposure (CS-exposure) and active-immune (via injections of β2-AR second extracellular loop peptides) rat models, we found that CS-exposed rats showed higher serum β2-AAb levels than control rats before alveolar airspaces became enlarged. Active-immune rats showed increased serum β2-AAb levels, and exhibited alveolar airspace destruction. CS-exposed-active-immune treated rats showed more extensive alveolar airspace destruction than rats undergoing CS-exposure alone. In our current clinical studies, we showed that plasma β2-AAb levels were positively correlated with the RV/TLC (residual volume/total lung capacity) ratio (r = 0.455, p < 0.001) and RV%pred (residual volume/residual volume predicted percentage, r = 0.454, p < 0.001) in 50 smokers; smokers with higher plasma β2-AAb levels exhibited worse alveolar airspace destruction. We suggest that increased circulating β2-AAbs are associated with smoking-related emphysema. PMID:28262783

  19. Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases.

    Science.gov (United States)

    Wallukat, Gerd; Schimke, Ingolf

    2014-05-01

    Agonistic autoantibodies (AABs) against G-protein-coupled receptor (GPCR) are present mainly in diseases of the cardiovascular system or in diseases associated with cardiovascular disturbances. The increasing knowledge about the role of autoantibodies against G-protein-coupled receptor (GPCR-AABs) as pathogenic drivers, the resulting development of strategies aimed at their removal or neutralization, and the evidenced patient benefit associated with such therapies have created the need for a summary of GPCR-AAB-associated diseases. Here, we summarize the present knowledge about GPCR-AABs in cardiovascular diseases. The identity of the GPCR-AABs and their prevalence in each of several specific cardiovascular diseases are documented. The structure of GPCR is also briefly discussed. Using this information, differences between classic agonists and GPCR-AABs in their GPCR binding and activation are presented and the resulting pathogenic consequences are discussed. Furthermore, treatment strategies that are currently under study, most of which are aimed at the removal and in vivo neutralization of GPCR-AABs, are indicated and their patient benefits discussed. In this context, immunoadsorption using peptides/proteins or aptamers as binders are introduced. The use of peptides or aptamers for in vivo neutralization of GPCR-AABs is also described. Particular attention is given to the GPCR-AABs directed against the adrenergic beta1-, beta2-, and α1-receptor as well as the muscarinic receptor M2, angiotensin II-angiotensin receptor type I, endothelin1 receptor type A, angiotensin (1-7) Mas-receptor, and 5-hydroxytryptamine receptor 4. Among the diseases associated with GPCR-AABs, special focus is given to idiopathic dilated cardiomyopathy, Chagas' cardiomyopathy, malignant and pulmonary hypertension, and kidney diseases. Relationships of GPCR-AABs are indicated to glaucoma, peripartum cardiomyopathy, myocarditis, pericarditis, preeclampsia, Alzheimer's disease, Sj

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

    Science.gov (United States)

    Dieker, Jürgen; Berden, Jo H.; Bakker, Marinka; Briand, Jean-Paul; Muller, Sylviane; Voll, Reinhard; Sjöwall, Christopher; Herrmann, Martin; Hilbrands, Luuk B.; van der Vlag, Johan

    2016-01-01

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis. PMID:27780265

  1. Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

    Science.gov (United States)

    Tripathi, Prashant; Moinuddin; Dixit, Kiran; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif

    2014-07-01

    Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified with peroxynitrite, generated by quenched flow process. Modifications incurred in plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy, circular dichroism, HPLC and melting temperature studies. Binding characteristics and specificity of antibodies from diabetes patients were analyzed by direct binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid resulted in the formation of strand breaks and base modification. The major compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a specific marker for peroxynitrite induced DNA damage in inflamed tissues. The concentration of 8-nitroguanine was found to be 3.8 μM. Sera from diabetes type 1 patients from different age groups were studied for their binding to native and peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA results showed higher recognition of peroxynitrite modified plasmid, as compared to the native form, by auto-antibodies present in diabetes patients. The preferential recognition of modified plasmid by diabetes autoantibodies was further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite-modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA isolated from diabetes patients.

  2. Electrochemical biosensor for quantitation of anti-DNA autoantibodies in human serum.

    Science.gov (United States)

    Rubin, Robert L; Wall, David; Konstantinov, Konstantin N

    2014-01-15

    Measurement of serum autoantibody is a critical tool in the diagnosis and management of autoimmune diseases. However, rapid and convenient methods at the point-of care have not been achieved in large part because any one antibody species is a heterogeneous and miniscule fraction of the total serum immunoglobulin displaying identical properties other than its antigen-binding specificity. The present system addresses these challenges by vacuum-mediated transport of diluted serum through an antigen-coated porous membrane. To measure anti-DNA autoantibodies, native DNA was immobilized into a poly(vinylidene fluoride) membrane pre-coated with a synthetic phenylalanine/lysine co-polymer. Flow-through of primary and peroxidase-conjugated secondary antibodies over the course of 3 min enhanced productive antibody-antigen interactions by bringing the reactants into close mutual proximity. Signal was quantified electrochemically during the enzymatic conversion of the tetramethylbenzidine substrate to a charge-transfer complex. The electrochemical signals generated by sera from patients with systemic lupus erythematosus using this device showed good quantitative correlation with a standard enzyme-linked immunosorbent assay and displayed similar detection limits. Inter- and intra-assay variability and electrode uniformity were favorable as was a two-month test of the stability of the DNA-coated membrane. While refining the fluidics requirements of this biosensor will be needed, its capacity to quantify over the course of 30 min anti-DNA antibodies in fresh human serum without background reactivity of normal serum makes this a promising technology as a point-of care device of clinical utility.

  3. 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.

  4. Type 1 diabetes risk and autoantibody positivity in Sardinian migrants in the province of Pavia

    Directory of Open Access Journals (Sweden)

    Gian F. Bottazzo

    2009-07-01

    Full Text Available Background: Type 1 diabetes is an autoimmune disease. Genetics as well as environmental factors seem to play a role in the pathogenesis of type 1 diabetes. Aims: We sought to investigate the possible relationship between migration from Sardinia to a low incidence area of type 1 diabetes (Lombardy and the prevalence of autoantibody positivity. Methods: We enrolled 554 Sardinian immigrants and 226 offspring. All subjects underwent a complete anamnestic evaluation. Fasting blood glucose, HbA1c, GADA and IA-2 were measured in all study participants. Additionally, the presence of risk haplotypes (HLA-DR3 –DR4 and DQB1/0302 was determined. After seven-year follow-up, high genetic risk and/or autoantibody positivity subjects were re-evaluated. Results: Among Sardinian immigrants, prevalence of type 1 diabetes was 0.9%, while in the offspring group was 0.4%. After removing type 1 diabetic patients, GADA prevalence was 2.4% in the immigrant group and 3.8% among offspring. Among Sardinian migrants, IA-2 prevalence was 0.7%, while all offspring were IA-2 negative. After seven-year follow-up, 85.7% of GADA positive migrants had persistent GADA positivity. Two GADA negative offspring subjects turned positive. None of the study participants developed diabetes during follow-up. Conclusions: The present study showed a higher prevalence of GADA positivity within Sardinian immigrants at high genetic risk: GADA positivity may represent the first detectable phase of type 1 diabetes. After a 7 year follow-up, none of the high genetic/antibody risk group subjects developed type 1 diabetes. However, it seems reasonable to strictly control high-risk individuals in order to diagnose subclinical diabetes.

  5. 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.

  6. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    Science.gov (United States)

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  7. Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings.

    Science.gov (United States)

    Baysal-Kirac, Leyla; Tuzun, Erdem; Erdag, Ece; Ulusoy, Canan; Vanli-Yavuz, Ebru Nur; Ekizoglu, Esme; Peach, Sian; Sezgin, Mine; Bebek, Nerses; Gurses, Candan; Gokyigit, Aysen; Vincent, Angela; Baykan, Betul

    2016-03-01

    Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

  8. Inhibition of neutrophil-mediated production of reactive oxygen species (ROS) by endothelial cells is not impaired in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis patients

    NARCIS (Netherlands)

    Al Laham, F.; Kaelsch, A. -I.; Heinrich, L.; Birck, R.; Kallenberg, C. G. M.; Heeringa, P.; Yard, B.

    2010-01-01

    P>Leucocyte transendothelial migration is strictly regulated to prevent undesired inflammation and collateral damage of endothelial cells by activated neutrophils/monocytes. We hypothesized that in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) patients' dysregulation

  9. 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

  10. 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....

  11. 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.

  12. Autoantibody profiles in two patients with non-autoimmune muscle disease implicate a role for gliadin autoreactivity.

    Science.gov (United States)

    Olsen, Nancy J; Prather, Heidi; Li, Quan-Zhen; Burns, Dennis K

    2010-03-01

    The objective of this case study was to characterize autoreactivity in two patients with non-autoimmune forms of muscle disease who had positivity for antinuclear antibodies (ANA) and Ro (SSA) autoantibodies. Serum samples from these two patients were applied to an autoantigen protein array with more than 70 specificities and were compared to samples from healthy controls and patients with systemic lupus erythematosus. Both myopathy patients had high levels of gliadin autoreactivity in serum and one patient had an overall autoantibody profile with lupus-like features. The findings suggest that some disorders of muscle that are considered non-autoimmune, may in fact have autoimmune features. Further examination of the role of subclinical gluten autoreactivity in the pathogenesis of myopathy syndromes has the potential to suggest improved approaches to diagnosis and treatment of these conditions.

  13. GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA)

    OpenAIRE

    Towns, Roberto; Pietropaolo, Massimo

    2011-01-01

    One of the hallmarks of autoimmune diabetes is the presence of adaptive responses directed to neuroendocrine proteins. One of these proteins is glutamic acid decarboxylase (GAD). While GAD is widely distributed in neuroendocrine tissues, its specific significance in diabetes has paralleled the advances in understanding humoral and cellular immunity in Type 1 diabetes (T1D) and in a subset of Type 2 diabetes (T2D), going from the seminal discoveries of islet autoantibodies to the development a...

  14. Anti-PLA2R autoantibodies in serum and Ig G subclass deposits on glomeruli in undetermined atypical membranous nephropathy

    Institute of Scientific and Technical Information of China (English)

    陈幸

    2014-01-01

    Objective To investigate the characteristic of autoantibodies of M-type phospholipase A2 receptor(PLA2R)in serum and the glomerular Ig G subclass deposits in undetermined atypical membranous nephropathy(MN)patients.Methods From Feb 2004 to Nov 2011,53 cases diagnosed as MN by kidney puncture biopsy in our hospital were included into the study.There were 20

  15. 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

  16. Levels of Folate Receptor Autoantibodies in Maternal and Cord Blood and Risk of Neural Tube Defects in a Chinese population

    Science.gov (United States)

    Yang, Na; Wang, Linlin; Finnell, Richard H.; Li, Zhiwen; Jin, Lei; Zhang, Le; Cabrera, Robert M.; Ye, Rongwei; Ren, Aiguo

    2016-01-01

    Background After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. Methods From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Results Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71–6.80) and 5.53-fold increased odds (95% CI, 1.90–16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35–2.75) and 3.49 (95% CI, 1.45–8.39), respectively. A dose–response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. Conclusion Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose–response manner. PMID:27166990

  17. An intrinsic B cell defect is required for the production of autoantibodies in the lpr model of murine systemic autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Sobel, E.S.; Katagiri, T.; Katagiri, K.; Morris, S.C.; Cohen, P.L.; Eisenberg, R.A. (Univ. of North Carolina, Chapel Hill (USA))

    1991-06-01

    Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that of human systemic lupus erythematosus. The unusual T cell phenotype of the expanded lymphocyte population and the T-dependence of several antibodies in this strain have suggested that primary T cell abnormalities underlie the autoimmune syndrome. Using double chimeras, we now show that expression of the lpr gene in B cells is absolutely necessary for autoantibody production. Combinations of anti-Thy 1.2 + C' treated bone marrow from congenic strains of C57BL/6 mice, differing only at the immunoglobulin heavy chain (Igh) and lpr loci, were transferred into lethally irradiated B6/lpr mice. Double chimerism was documented by allotype-specific surface IgD and IgM immunofluorescence assay of peripheral blood and by allotype-specific enzyme-linked immunosorbent assay for total IgM in serum. Despite the presence of both +/+ and lpr B cells, IgM and IgG2a anti-chromatin as well as IgM anti-IgG were entirely the products of lpr B cells. Total serum IgG2a and IgG1 were also dominated by the lpr phenotype but not to the same extent. A similar experiment using B6/lpr-Igha recipients confirmed these findings. Additional experiments in which B6/lpr recipients were infused with ratios of donor bone marrow favoring B6.C20 +/+ over B6/lpr showed that even though +/+ B cells were overrepresented, autoantibodies were only of the lpr allotype. In addition, in the presence of lpr B cells, normal B cells showed little response to an exogenous, T cell-dependent antigen. The data thus indicate that lpr B cells manifest an intrinsic abnormality which is essential for autoantibody production in the lpr model.

  18. Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies.

    Science.gov (United States)

    Meulenbroek, Elisabeth M; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S; Wouters, Diana

    2015-11-01

    In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient's erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients' sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients' sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients' erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy.

  19. IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis.

    Science.gov (United States)

    Merlo, Lauren M F; Pigott, Elizabeth; DuHadaway, James B; Grabler, Samantha; Metz, Richard; Prendergast, George C; Mandik-Nayak, Laura

    2014-03-01

    Rheumatoid arthritis and other autoimmune disorders are associated with altered activity of the immunomodulatory enzyme IDO. However, the precise contributions of IDO function to autoimmunity remain unclear. In this article, we examine the effect of two different IDO enzymes, IDO1 and IDO2, on the development of autoimmune arthritis in the KRN preclinical model of rheumatoid arthritis. We find that IDO2, not IDO1, is critical for arthritis development, providing direct evidence of separate in vivo functions for IDO1 and IDO2. Mice null for Ido2 display decreased joint inflammation relative to wild-type mice owing to a reduction in pathogenic autoantibodies and Ab-secreting cells. Notably, IDO2 appears to specifically mediate autoreactive responses, but not normal B cell responses, as total serum Ig levels are not altered and IDO2 knockout mice are able to mount productive Ab responses to model Ags in vitro and in vivo. Reciprocal adoptive transfer studies confirm that autoantibody production and arthritis are modulated by IDO2 expression in a cell type extrinsic to the T cell. Taken together, our results, provide important insights into IDO2 function by defining its pathogenic contributions to autoantibody-mediated autoimmunity.

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

    Science.gov (United States)

    Vorobyev, Artem; Ujiie, Hideyuki; Recke, Andreas; Buijsrogge, Jacqueline J A; Jonkman, Marcel F; Pas, Hendri H; Iwata, Hiroaki; Hashimoto, Takashi; Kim, Soo-Chan; Hoon Kim, Jong; Groves, Richard; Samavedam, Unni; Gupta, Yask; Schmidt, Enno; Zillikens, Detlef; Shimizu, Hiroshi; Ludwig, Ralf J

    2015-06-01

    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 different epitopes is pathogenically relevant. To address this issue, we generated recombinant proteins covering the entire NC1 domain. IgG reactivity with these proteins was analyzed in sera of 69 EBA patients. Most recognized clusters of epitopes throughout the NC1 domain. No correlation was detected between antibody specificity and clinical phenotype. To study the pathogenicity of antibodies specific to different NC1 subdomains, rabbit antibodies were generated. All these antibodies caused dermal-epidermal separation ex vivo. Antibodies against two of these subdomains were injected into mice carrying null mutations of mouse COL7 and the human COL7 transgene and induced subepidermal blisters. We here document that autoantibodies to COL7, independent of the targeted epitopes, induce blisters both ex vivo and in vivo. In addition, using COL7-humanized mice, we provide in vivo evidence of pathogenicity of autoantibodies binding to human COL7.

  1. An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice.

    Science.gov (United States)

    Nelson, R K; Gould, K A

    2016-02-01

    Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell-specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB × NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4(+) and CD8(+) T cells, the proportion of activated CD4(+) T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cell apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system.

  2. Diagnostic sensitivity of thyroid autoantibodies assessed in a population-based, cross-sectional study in adults.

    Science.gov (United States)

    Bosi, Emanuele; Bianchi, Roberto; Ruotolo, Giacomo; Bazzigaluppi, Elena; Belloni, Cristina; Calori, Giliola; Girardi, Anna Maria; Garancini, Maria Paola; Scavini, Marina

    2010-11-01

    The aim of this study was to estimate the diagnostic sensitivity of thyroid autoantibodies in individuals with a case-mix of subjects with thyroid disease representing that of the general population. We measured thyroid microsome (TMA), thyroid peroxidase (TPO), thyroglobulin (TGA) and thyroid-stimulating hormone (TSH) receptor (TRA) autoantibodies in subjects in the bottom (hyperthyroid end) and top (hypothyroid end) four percentiles of the TSH distribution from among participants in a population-based survey of individuals aged ≥40 years (the Cremona Study). TMA and TPO were the most sensitive autoantibodies in subjects in both the bottom percentiles (19.8% and 18.5%, respectively) and the top percentiles (51.2% and 53.8%, respectively) of the TSH distribution. TMA and TPO showed good agreement (kappa statistics 87.8%, 95% CI 80.1-95.5%) at both ends of the TSH distribution. TGA were the next most sensitive marker, although seldom detected if TMA or TPO were not present. TRA were detected only at the extremes of the TSH distribution (1st percentile, 31.8%; 100th percentile, 25.0%). We conclude that, among a case-mix of individuals with thyroid disease representing that of the general population, TMA and TPO are the most sensitive markers of thyroid disease. TGA only marginally increased the diagnostic sensitivity of TMA and TPO. TRA are sensitive markers of thyroid disease only at the extremes of thyroid function.

  3. 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.

  4. Measurement of ferritin and anti-ferritin autoantibodies in serum and colostrum of Holstein and Japanese Black cows.

    Science.gov (United States)

    Kanno, Yoshiya; Ohtsuka, Hiromichi; Yoshikawa, Yasunaga; Watanabe, Kiyotaka; Orino, Koichi

    2013-07-01

    Anti-ferritin autoantibody is a ferritin-binding protein commonly found in mammals; it is thought to form an immune complex with ferritin and thereby mediate the rapid clearance of circulating ferritin. The aim of this study is to determine concentrations of ferritin and anti-ferritin autoantibodies (immunoglobulin (Ig)M, IgG and IgA) in serum and colostrum of Holstein (H) and Japanese Black (JB) cows within 24 h of normal calving. Blood and colostrum samples were collected from cows of various ages (2-11 years) and calving number (1-8 live births). Mean ferritin concentrations were higher in colostrum than in serum for both breeds, and higher colostrum ferritin concentrations were found in H than JB cows. IgA antibodies in serum and colostrum from both breeds had negligible ferritin-binding activity. For both breeds, IgM and IgG antibodies had higher ferritin-binding activity in colostrum than in serum. There was a significant correlation between IgM and IgG ferritin-binding activities in serum and colostrum of H and JB cows. These results suggest that ferritin and IgM and IgG autoantibodies are actively transferred from the blood stream to the colostrum at prepartum or early lactation.

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

    Directory of Open Access Journals (Sweden)

    Satoko Arai

    2013-04-01

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

  6. 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

  7. 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

  8. A rapid method of detecting autoantibody against FcεRIα for chronic spontaneous urticaria.

    Directory of Open Access Journals (Sweden)

    Mey-Fann Lee

    Full Text Available BACKGROUND: Chronic spontaneous urticaria (CU is a common skin disorder, with an estimated prevalence of 0.5-1.8% in most populations. Around 30-50% of CU patients have an autoimmune etiology, with autoantibodies (autoAbs against IgE, FcεRIα, and FcεRII/CD23. Although the in vivo autologous serum skin test (ASST and in vitro histamine release/activation assay are the most frequently used screening methods, these two have many limitations and do not directly measure susceptible autoAbs. This study aimed to establish an in vitro rapid screening test using recombinant autoantigen FcεRIα(rFcεRIα to improve the diagnosis of autoimmune urticaria. METHODS: Forty patients with CU and 20 healthy individuals were enrolled. After PCR-based cloning and the production of extracellular fragments of the FcεRIα protein using the E. coli expression system, serum autoAb to rFcεRIα was evaluated using in-house ELISA and rapid immunodot test. RESULTS: In ELISA-based detection, 14 out of 20 CU-ASST(+ patients exhibited anti- FcεRIα responses, whereas five of the 20 CU-ASST(- and two of the 20 non-CU patients showed autoantibody background in the assay. For the immunodot test, 55% (11/20 of the CU-ASST(+ sera exhibited anti-FcεRIα reactivity. There was no false positive among the CU-ASST(- and non-CU groups. Using clinical urticaria plus ASST(+ as the gold standard, in-house ELISA had 70% sensitivity, 82.5% specificity, and positive likelihood ratio of 4, while immunodot had 55% sensitivity, 100% specificity, and positive likelihood ratio >55. CONCLUSIONS: This study has developed a rapid immunodot method with high specificity for detecting autoAb to FcεRIαin patients with CU. Preliminary data indicates that this immunodot technique has the potential to be a routine diagnostic assay for autoimmune CU.

  9. Effects of autoantibodies against β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+ currents

    Institute of Scientific and Technical Information of China (English)

    Kun Liu; Yu-Hua Liao; Zhao-Hui Wang; Shu-Li Li; Ming Wang; Ling-Lan Zeng; Ming Tang

    2004-01-01

    AIM: To investigate the effects of autoantibodies against β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+ currents.METHODS: Fifteen samples of autoantibodies against β1-adrenoceptor positive sera of patients with hepatitis virus myocarditis were obtained and IgGs were purified by octanoic acid extraction. Binding of autoantibodies against β1-adrenoceptor to guinea pig cardiac myocytes was examined by immunofiuorescence. Using the patch clamp technique,the effects on the action potential and ICa-L of guinea pig cardiac myocytes caused by autoantibodies against β1-adrenoceptor in the absence and presence of metoprolol were investigated.Cell toxicity was examined by observing cell morphology and permeability of cardiac myocytes to trypan blue.RESULTS: The specific binding of autoantibodies against β1-adrenoceptor to guinea pig cardiomyocytes was observed.Autoantibodies against β1-adrenoceptor diluted at 1:80prolonged APD20, APD50 and APD90 by 39.2%, 29.1% and 15.2% respectively, and only by 7.2%, 5.3% and 4.1%correspondingly in the presence of 1 μmol/L metoprolol.Autoantibodies against β1-adrenoceptor diluted at 1:80,1:100 and 1:120 significantly increased the ICa-L peak current amplitude at 0 mV by 55.87±4.39%, 46.33±5.01% and 29.29±4.97% in a concentration-dependent manner. In contrast, after blocking of β1-adrenoceptors (1 μmol/L metoprolol), autoantibodies against β1-adrenoceptor diluted at 1:80 induced a slight increase of ICa-L peak amplitude only by 6.81±1.61%. A large number of cardiac myocytes exposed to high concentrations of autoantibodies against β1-adrenoceptor (1:80 and 1:100) were turned into rounded cells highly permeable to trypan blue.CONCLUSION: Autoantibodies against β1-adrenoceptor may result in arrhythmias and/or impairment of myocardiums in HVM, which would be mediated by the enhancement of ICa-L.

  10. Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case-control study.

    Science.gov (United States)

    Toulis, Konstantinos A; Goulis, Dimitrios G; Tsolakidou, Konstantina; Hilidis, Ilias; Fragkos, Marios; Polyzos, Stergios A; Gerofotis, Antonios; Kita, Marina; Bili, Helen; Vavilis, Dimitrios; Daniilidis, Michail; Tarlatzis, Basil C; Papadimas, Ioannis

    2013-08-01

    We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

  11. CUTANEOUS LUPUS ERYTHEMATOSUS WITH AUTOANTIBODIES COLOCALIZING WITH GLIAL FIBRILLARY ACIDIC PROTEIN

    Directory of Open Access Journals (Sweden)

    Abreu-Velez Ana Maria

    2011-01-01

    Full Text Available Background: Discoid lupus erythematosus (DLE is a chronic, inflammatory skin disorder, presenting with scarring lesions predominating on sun exposed areas of the face and scalp. Case Report: A 43-year-old African American female was evaluated for possible DLE. Methods: Skin biopsies for hematoxylin and eosin (H&E examination, as well as for direct immunofluorescence (DIF analysis were performed. Results: H&E staining demonstrated classic features of cutaneous lupus erythematosus, with the pertinent presence of perineural lymphohistiocitic infiltrates, especially those associated with skin appendices. DIF revealed strong deposits of immunoglobulins IgG, IgM, fibrinogen and Complement/C3, present in a shaggy, linear pattern at or near the basement membrane zone (BMZ of selected eccrine and sebaceous glands, and around some blood vessels. The BMZ positivity in these structures consistently colocalized with positive staining in multiple, punctate areas for glial fibrillary acidic protein (GFAP, including within cytoid bodies. Conclusions:. The observed colocalization of the patient’s autoantibodies in cutaneous lupus with GFAP may have pathophysiologic relevance. Specifically, our data could be consistent with previously described DLE patients with or without overt central nervous system manifestations, or could represent an epiphenomenon. Additional, larger studies are needed to satisfactorily address this possibility.

  12. Inflammatory Bowel Disease in Indo-Canadians with and without Antineutrophil Cytoplasmic Autoantibodies

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    Hugh James Freeman

    2000-01-01

    Full Text Available A sequentially evaluated cohort of Indo-Canadians with either ulcerative colitis or Crohn’s disease were prospectively examined for antineutrophil cytoplasmic autoantibodies (ANCA. Of 84 patients, 62 had ulcerative colitis and 22 had Crohn’s disease. About one-third were born in Canada, and two-thirds were migrants from India or other countries, particularly East African nations. There was a disease-based and geographically based male predominance. The mean age of Canadian-born patients was significantly less than that of those born in other countries. Moreover, for migrants, the mean duration of residence in Canada before developing disease was 8.9 years for Crohn’s disease patients and 13.5 years for ulcerative colitis patients. Moderate to severe disease was present; virtually all those with Crohn’s disease had colonic involvement, and most of those with ulcerative colitis had extensive colonic disease. Overall, 40 of 84 (48% were seropositive for ANCA, including a majority of those with ulcerative colitis but not Crohn’s disease. In addition, eight had cytoplasmic ANCA, a reported seromarker for extensive colitis. Seropositive and seronegative patients were similar in age, sex, birth or duration of residence in Canada, site and severity of disease, familial history and complications, including pouchitis. This study supports the view that these diseases arise in individuals with a genetic predisposition following exposure to some, as yet unknown, environmental factor.

  13. 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

    . 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......A-positive 65 vs 39% in IA2betaA-negative, p=0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p=0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2betaA, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal...

  14. Higher Sensitivity and Earlier Identification of Celiac Disease Autoimmunity by a Nonradioactive Assay for Transglutaminase Autoantibodies

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zhao

    2016-01-01

    Full Text Available Higher sensitive transglutaminase autoantibody (TGA assay will detect the onset of celiac disease (CD autoimmunity earlier. In developing a nonradioactive assay for TGA, we utilized electrochemiluminescence (ECL technology and compared it to a high-performance radioimmunoassay (RIA currently being used to screen patients with type 1 diabetes (T1D and genetically at-risk individuals for CD. We selected 183 T1D patients with 60 patients having received biopsy and analyzed 396 sequential samples from 73 young children longitudinally followed up with TGA seroconversion, with 27 undergoing biopsy. In addition, 112 age-matched healthy control subjects were included in the study. With the 99th percentile of specificity, the ECL assay detected significantly more TGA positivity among patients with T1D (133/183 than RIA (114/183 and more of the sequential samples (34% from 73 children than RIA (18%. The TGA assay performed by ECL was positive in all 59 subjects with villous atrophy. Among 73 longitudinally followed up children, ECL assay had earlier detection of TGA on 34 children by a mean of 2.5 years. In conclusion, the new TGA assay by ECL has a higher sensitivity than the current RIA assay and may better predict the onset of CD.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  16. Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.

    Science.gov (United States)

    Muryoi, T; Kasturi, K N; Kafina, M J; Cram, D S; Harrison, L C; Sasaki, T; Bona, C A

    1992-04-01

    We have generated for the first time monoclonal antibodies (mAbs) specific for topoisomerase I (topo I) from scleroderma patients, and tight skin mice which develop a scleroderma-like syndrome. The epitope specificity of these antibodies has been determined using a series of fusion proteins containing contiguous portions of topo I polypeptide. Western blot analysis demonstrated that both human and mouse mAbs bound strongly to fusion protein C encompassing the NH2-terminal portion of the enzyme, and weakly to fusion proteins F and G containing regions close to the COOH-terminal end of the molecule. This crossreactivity is related to a tripeptide sequence homology in F, G, and C fusion proteins. It is interesting that a pentapeptide sequence homologous to that in fusion protein C was identified in the UL70 protein of cytomegalovirus, suggesting that activation of autoreactive B cell clones by molecular mimicry is possible. Both human and mouse mAbs exhibiting the same antigen specificity, also share an interspecies cross-reactive idiotope. These data suggest that B cell clones producing antitopo autoantibodies present in human and mouse repertoire are conserved during phylogeny, and are activated during the development of scleroderma disease.

  17. Thyroid Hormones, Autoantibodies, Ultrasonography, and Clinical Parameters for Predicting Thyroid Cancer

    Science.gov (United States)

    He, Lin-zheng; Zeng, Tian-shu; Pu, Lin; Pan, Shi-xiu; Xia, Wen-fang; Chen, Lu-lu

    2016-01-01

    Our objective was to evaluate thyroid nodule malignancy prediction using thyroid function tests, autoantibodies, ultrasonographic imaging, and clinical data. We conducted a retrospective cohort study in 1400 patients with nodular thyroid disease (NTD). The thyroid stimulating hormone (TSH) concentration was significantly higher in patients with differentiated thyroid cancer (DTC) versus benign thyroid nodular disease (BTND) (p = 0.004). The receiver operating characteristic curve of TSH showed an AUC of 0.58 (95% CI 0.53–0.62, p = 0.001), sensitivity of 74%, and specificity of 57% at a cut-off of 1.59 mIU/L. There was an incremental increase in TSH concentration along with the increasing tumor size (p < 0.001). Thyroglobulin antibody (TgAb) concentration was associated with an increased risk of malignancy (p = 0.029), but this association was lost when the effect of TSH was taken into account (p = 0.11). Thyroid ultrasonographic characteristics, including fewer than three nodules, hypoechoic appearance, solid component, poorly defined margin, intranodular or peripheral-intranodular flow, and punctate calcification, can be used to predict the risk of thyroid cancer. In conclusion, our study suggests that preoperative serum TSH concentration, age, and ultrasonographic features can be used to predict the risk of malignancy in patients with NTD. PMID:27313612

  18. 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

    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...

  19. Do associated auto-antibodies influence the outcome of myasthenia gravis after thymectomy?

    Science.gov (United States)

    Keijzers, Marlies; Damoiseaux, Jan; Vigneron, Alain; Bodart, Nicolas; Kessels, Alfons; Dingemans, Anne-Marie C; Hochstenbag, Monique; Maessen, Jos; De Baets, Marc

    2015-01-01

    Myasthenia gravis (MG) is a neuromuscular autoimmune disease, where antibodies against the acetylcholine receptor destroy this receptor. The role of thymectomy in the treatment of MG remains controversial. Because of the frequent association with other autoimmune diseases, we hypothesized that patients with multiple autoantibodies (autoAbs) might have a lower chance of reaching complete stable remission after thymectomy. We analyzed sera of 85 MG patients who underwent a thymectomy between April 2004 and December 2012. We used four different immunodot kits (D-Tek, Mons, Belgium): ANA25 Quantrix, Synthetase 10 Diver, Myositis 7 Diver and Liver 10 profile Diver, all automatized on the BlueDiver Instrument (D-Tek). The Myasthenia Gravis Foundation of America (MGFA) postintervention status was used to determine the outcome after thymectomy. AutoAbs other than anti-acetylcholine receptor (AChR) antibodies were detected in 29.4% of the patients of whom 16.5% clinically had a second autoimmune disease. In none of the seronegative patients other autoAbs were detected. No significant difference was observed in the 3-years remission rate after thymectomy in patients with or without antibodies other than anti-AChR antibodies. Although these autoAbs do not predict outcome in our MG patient cohort, screening for multiple autoAbs in MG patients might be warranted to identify patients with additional autoimmune diseases.

  20. Topically Applied Hsp90 Blocker 17AAG Inhibits Autoantibody-Mediated Blister-Inducing Cutaneous Inflammation.

    Science.gov (United States)

    Tukaj, Stefan; Bieber, Katja; Kleszczyński, Konrad; Witte, Mareike; Cames, Rebecca; Kalies, Kathrin; Zillikens, Detlef; Ludwig, Ralf J; Fischer, Tobias W; Kasperkiewicz, Michael

    2017-02-01

    Cell stress-inducible Hsp90 has been recognized as key player in mediating inflammatory responses. Although its systemic blockade was successfully used to treat autoimmune diseases in preclinical models, efficacy of a topical route of Hsp90 inhibitor administration has so far not been evaluated in chronic inflammatory and autoimmune-mediated dermatoses. Here, effects of the Hsp90 blocker 17-allylamino-demethoxygeldanamycin (17AAG) applied topically to the skin were determined in experimental inflammatory epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-induced blistering skin disease. Topical 17AAG ameliorated clinical disease severity when given before or during the occurrence of skin lesions without causing cutaneous or systemic toxicity in mice with antibody transfer- and immunization-induced EBA. In both EBA models and in the setting of locally induced inflammation, topical 17AAG treatment was associated with (i) reduced neutrophilic infiltrates, (ii) decreased NF-κB activation, (iii) lowered expression of matrix metalloproteinases and Flii, and (iv) induction of anti-inflammatory Hsp70 in the skin. Our results suggest that topical delivery of Hsp90 antagonists, offering the benefit of a reduced risk of systemic adverse effects of Hsp90 inhibition, may be useful for the control of EBA and possibly other related inflammatory skin disorders.

  1. Autoantibodies to tailor-made panels of tumor-associated antigens in breast carcinoma.

    Science.gov (United States)

    Piura, Ettie; Piura, Benjamin

    2011-01-01

    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.

  2. Autoantibodies to IA-2 in insulin-dependent diabetes mellitus. Measurements with a new immunoprecipitation assay.

    Science.gov (United States)

    Masuda, M; Powell, M; Chen, S; Beer, C; Fichna, P; Rees Smith, B; Furmaniak, J

    2000-01-20

    An immunoprecipitation assay for autoantibodies (Abs) to the human islet cell antigen IA-2 has been developed using 125I-labelled recombinant IA-2 expressed in E. coli. With this assay IA-2 Abs were detected in 103/217 (47%) of IDDM patients of different ages and with different disease duration. IA-2 Ab prevalence was higher in younger patients (at the age of 15 years or below) with the recent onset IDDM (64/113; 57%) compared to patients above the age of 15 years (11/25; 44%). One of 40 (2.5%) Graves' disease patients and five of 204 (2.5%) of NIDDM patients were also positive. IA-2 Abs were not detected in sera from patients with Hashimoto's thyroiditis (n=32), myasthenia gravis (n=20) or systemic lupus erythematosus (n=10). IA-2 Ab measurements based on 125I-labelled IA-2 showed a good correlation with the results of an immunoprecipitation assay based on 35S-labelled IA-2 produced in the in vitro transcription/translation system (r=0.78; n=113; pAb testing in IDDM. Overall, the IA-2 Ab assay based on 125I-labelled recombinant IA-2 showed good sensitivity, precision and specificity which, combined with an easy and convenient protocol, makes it attractive for routine use.

  3. A systems immunology approach to the host-tumor interaction: large-scale patterns of natural autoantibodies distinguish healthy and tumor-bearing mice.

    Directory of Open Access Journals (Sweden)

    Yifat Merbl

    Full Text Available Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1 mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2 the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3 curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase. Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System

  4. Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis

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    Marcela Gran Pina Cruellas

    2013-07-01

    Full Text Available OBJECTIVE: To analyze the prevalence of myositis-specific and myositis-associated autoantibodies and their clinical correlations in a large series of patients with dermatomyositis/polymyositis. METHOD: This cross-sectional study enrolled 127 dermatomyositis cases and 95 polymyositis cases. The disease-related autoantibody profiles were determined using a commercially available blood testing kit. RESULTS: The prevalence of myositis-specific autoantibodies in all 222 patients was 34.4%, whereas myositis-associated autoantibodies were found in 41.4% of the patients. The most frequently found autoantibody was anti-Ro-52 (36.9%, followed by anti-Jo-1 (18.9%, anti-Mi-2 (8.1%, anti-Ku (4.1%, anti-SRP (3.2%, anti-PL-7 (3.2%, anti-PL-12 (2.7%, anti-PM/Scl75 (2.7%, and anti-PM/Scl100 (2.7%. The distributions of these autoantibodies were comparable between polymyositis and dermatomyositis, except for a higher prevalence of anti-Jo-1 in polymyositis. Anti-Mi-2 was more prevalent in dermatomyositis. Notably, in the multivariate analysis, anti-Mi-2 and anti-Ro-52 were associated with photosensitivity and pulmonary disorders, respectively, in dermatomyositis. Anti-Jo-1 was significantly correlated with pulmonary disorders in polymyositis. Moreover, anti-Ro-52 was associated with anti-Jo-1 in both diseases. No significant correlation was observed between the remaining autoantibodies and the clinical and/or laboratory findings. CONCLUSIONS: Our data are consistent with those from other published studies involving other populations, although certain findings warrant consideration. Anti-Ro-52 and anti-Jo-1 were strongly associated with one another. Anti-Ro-52 was correlated with pulmonary disorders in dermatomyositis, whereas anti-Jo-1 was correlated with pulmonary alterations in polymyositis.

  5. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay.

    Science.gov (United States)

    Miyakawa, Hiroshi; Kawashima, Yumi; Kitazawa, Eriko; Kawaguchi, Naomi; Kato, Takashi; Kikuchi, Kentaro; Imai, Erika; Fujikawa, Hirotoshi; Hashimoto, Etsuko; Schlumberger, Wolfgang

    2003-08-01

    Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.

  6. The Human Autoantibody Response to Apolipoprotein A-I Is Focused on the C-Terminal Helix: A New Rationale for Diagnosis and Treatment of Cardiovascular Disease?

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    Sabrina Pagano

    Full Text Available Cardiovascular disease (CVD is the leading cause of death worldwide and new approaches for both diagnosis and treatment are required. Autoantibodies directed against apolipoprotein A-I (ApoA-I represent promising biomarkers for use in risk stratification of CVD and may also play a direct role in pathogenesis.To characterize the anti-ApoA-I autoantibody response, we measured the immunoreactivity to engineered peptides corresponding to the different alpha-helical regions of ApoA-I, using plasma from acute chest pain cohort patients known to be positive for anti-ApoA-I autoantibodies.Our results indicate that the anti-ApoA-I autoantibody response is strongly biased towards the C-terminal alpha-helix of the protein, with an optimized mimetic peptide corresponding to this part of the protein recapitulating the diagnostic accuracy for an acute ischemic coronary etiology (non-ST segment elevation myocardial infarction and unstable angina obtainable using intact endogenous ApoA-I in immunoassay. Furthermore, the optimized mimetic peptide strongly inhibits the pathology-associated capacity of anti-ApoA-I antibodies to elicit proinflammatory cytokine release from cultured human macrophages.In addition to providing a rationale for the development of new approaches for the diagnosis and therapy of CVD, our observations may contribute to the elucidation of how anti-ApoA-I autoantibodies are elicited in individuals without autoimmune disease.

  7. A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children

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    AL-Ayadhi Laila

    2011-06-01

    Full Text Available Abstract Background One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP auto-antibodies, in autism. Methods Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children. Results Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P Conclusions Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder.

  8. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

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    Frances Humby

    2009-01-01

    Full Text Available BACKGROUND: Follicular structures resembling germinal centres (GCs that are characterized by follicular dendritic cell (FDC networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA. However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i express activation-induced cytidine deaminase (AID, the enzyme required for somatic hypermutation and class-switch recombination (CSR of Ig genes; (ii support ongoing CSR and ACPA production; and (iii remain functional in a RA/severe combined immunodeficiency (SCID chimera model devoid of new immune cell influx into the synovium. METHODS AND FINDINGS: Using immunohistochemistry (IHC and quantitative Taqman real-time PCR (QT-PCR in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching was observed in synovial grafts expressing FDCs/CD21L

  9. Coumestrol inhibits autoantibody production through modulating Th1 response in experimental autoimmune thyroiditis

    Science.gov (United States)

    Zhao, Xuemin; Jin, Qian; Fan, Chenling; Li, Jing; Shan, Zhongyan; Teng, Weiping

    2016-01-01

    Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 ± 21.74 ng/ml and 135.07 ± 70.40 ng/ml, respectively. In addition, the mice (n = 14–16/group) were immunized twice with thyroglobulin (Tg) and Freund's adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-γ mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity. PMID:27384679

  10. Discrepancy between haemagglutination and radioimmunological techniques for measurement of serum thyroglobulin autoantibodies

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    Feldt-Rasmussen, U.; Perrild, H.; Bech, K.; Bliddal, H.; Date, J.; Hoeier Madsen, M.; Nordfang, O.; Ryder, L.P.; Thomsen, M.; Kappelgaard, E. (Dept. of Internal Medicine and Endocrinology, Herlev University Hospital, Dept. of Medicine E, Frederiksberg Hospital, Dept. of Clinical Chemistry, Odense University Hospital, Autoimmune Lab., Serum Institute, Tissue Typing Laboratory and Medical Dept. TA, Rigshospitalet, Copenhagen, Denmark)

    1983-01-01

    Recently, it has been suggested that in some patients with autoimmune thyroid diseases the tanned red cell (TRC) method for detection of thyroglobulin autoantibodies (TgAb) is negative where TgAb measured by radioimmunoassay (RIA) show positive values. To investigate this further, patients with thyroid diseaes, pernicious anaemia and a control group were studied for serum concentrations of TgAb by TRC and by quantitative RIA, calibrated against MRC Standard A65/93. Antibodies for microsomes (MAb) were measured immunofluoretically. There was in all patient groups Hashimoto's thyroiditis (n=41), Graves' disease (n=50), Idiopathic myxoedemia (n=12), euthyroid Graves' disease (n=7), pernicious anaemia (n=81) a discrepancy between TgAb measured by TRC and RIA, respectively, whereas there was a reasonable correlation between the presence of TgAb by RIA and the presence of MAb. A possible interference from antinuclear antibodies and rheumatoid factors was ruled out. There was no increased frequency of TgAb measured by RIA in the control group. Fractionation of TRC negative sera revealed macromolecular TRC-activity, whereas TgAb positive sera by both methods had almost exclusively RIA and TRC activiy corresponding to TgG. Based on these results and others it seems that the TRC method for measurement of serum TgAb is of limited diagnostic value. Furthermore, the TRC method is in many cases not sensitive for screening fo TgAb prior to measurement of serum Tg which is of importance as this method shows false values in the presence of TgAb due to methodologial interference.

  11. Follicle-stimulating hormone autoantibody is involved in idiopathic spermatogenic dysfunction

    Institute of Scientific and Technical Information of China (English)

    Bing Yao; Jian Wang; Wei Liang; Ying-Xia Cui; Yi-Feng Ge

    2008-01-01

    Aim: To detect the anti-follicle-stimulating hormone (FSH) antibody in idiopathic infertile patients and fertile subjects in order to determine the role of this antibody in patients with spermatogenic dysfunction. Methods: The anti-FSH antibody in serum was detected by an enzyme-linked immunosorbent assay (ELISA). The functional and structural integrity of the sperm membrane was evaluated with hypo-osmotic swelling (HOS) test and the ultrastructure of the spermatozoa was investigated by transmission electron microscopy (TEM). Results: The extent of positive FSH antibody in the patients with oligozoospermia and/or asthenozoospermia was significantly higher than that in the fertile subjects and infertile patients with normal sperm concentration and motility, but it was significantly lower than that in the patients with azoospermia. The extent of anti-FSH antibody in the patients with azoospermia was significantly greater than that in patients with oligospermia and/or asthenospermia, infertile people with normal sperm density and motility and fertile people. The hypo-osmotic swelling test showed that the percentage of HOS-positive spermatozoa (swollen) was 45.1% ± 3.5% in the FSH antibody-positive group and 59.1% ± 6.2% in the FSH antibody-negative control group. The percentage of functional membrane damage to spermatozoa was significantly higher in the anti-FSH antibody-positive group than in the control group. TEM showed that the outer acrosomal membrane was located far from the nucleus, and detachment of the acrosome was found in the FSH autoantibody-positive group. Conclusion:These data suggest that the presence of anti-FSH antibody is strongly correlated with the sperm quantity and quality in idiopathic male infertility. Anti-FSH antibody may be an important factor causing spermatogenic dysfunction and infertility.

  12. Occurrence of autoantibodies to cilia in lambs with a 'coughing syndrome'.

    Science.gov (United States)

    Niang, M; Rosenbusch, R F; Andrews, J J; Lopez-Virella, J; Kaeberle, M L

    1998-07-31

    A respiratory disease of lambs that has been termed the 'coughing syndrome' has been observed in the mid-western region of the United States of America. Mycoplasma ovipneumoniae (M. ovipneumoniae) and Mycoplasma arginini (M. arginini) were routinely isolated from the respiratory tract of lambs with this disease. A high level of antibodies reactive with ovine cilia of the upper respiratory tract was detected in the sera from many of the lambs in affected flocks but not in sera of lambs from unaffected flocks. The reactivity of these antibodies with cilia was demonstrated by ELISA and confirmed by indirect immunofluorescent staining and western immunoblotting. These antibodies were predominantly of the IgG isotype. They were distinct from cold or warm agglutinins and could be absorbed from the sera with cilia but not with antigens of common bacterial pathogens of the sheep respiratory tract including M. ovipneumoniae, M. arginini, Pasteurella haemolytica, Pasteurella multocida or Neisseria ovis. In addition, their occurrence appeared to be independent of the specific antibodies to M. ovipneumoniae and M. arginini. Western immunoblotting indicated that the antibodies were directed primarily against an antigen with apparent molecular weight of 50 kDa. In one flock from which serial serum samples were collected from the same lambs over a 10-month period, antibodies to ovine cilia developed before the onset of the clinical disease and persisted for a period of several months until most of the lambs had apparently recovered. However, colonization of the respiratory tract of the lambs by M. ovipneumoniae preceded the production of these antibodies. Sequential serum samples taken from another flock, with no known history of this coughing, showed no such antibodies throughout the sampling period. It is suggested that an immunopathologic mechanism involving production of autoantibodies directed against a ciliary antigen of the lambs could be a contributing factor to the

  13. Induction of autoantibody-producing cells after the coculture of haptenated and normal human mononuclear leukocytes.

    Science.gov (United States)

    Pisko, E J; Foster, S L; Turner, R A

    1981-10-01

    The coculture of normal human peripheral blood mononuclear leukocytes (PBL) and autologous mononuclear leukocytes coupled to the trinitrophenyl (TNP) hapten (TNP-PBL) was found to induce a polyclonal activation of antibody-producing cells. The polyclonal activation of antibody-producing cells was demonstrated by detecting the induction of cells producing antibody to sheep red blood cells using a complement-dependent, direct, hemolytic plaque-forming cell (PFC) assay. A ratio of four normal to one haptenated mononuclear leukocyte was found to be optimal for inducing the polyclonal activation of antibody-producing cell in these cultures. The plaque-forming cells assay in these experiments utilized monolayers of indicator red cells. Further evidence for the polyclonal induction of antibody-producing cells by TNP-PBL was provided by demonstrating PFC on monolayers of not only sheep red blood cells, but also autologous human red cells, bromelain-treated autologous red cells, TNP-coupled human and sheep red cells, and human autologous red cells coupled to human heat-aggregated IgG with chromic chloride. Thus cells secreting antibody to TNP, human red cells, and human IgG were induced. Anti-IgG and anti-human red cell-producing cells were first detected on Day 2 of culture and were still present on Day 9. Mononuclear leukocytes altered by chemical haptenation polyclonally stimulate normal mononuclear leukocytes to become antibody-producing cells. This polyclonal stimulation of antibody-producing cells includes cells producing antibodies to human IgG and human autologous red blood cells suggesting that autoantibody-producing cells are induced.

  14. Autoantibodies to αS1-casein are induced by breast-feeding.

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    Klaudia Petermann

    Full Text Available BACKGROUND: The generation of antibodies is impaired in newborns due to an immature immune system and reduced exposure to pathogens due to maternally derived antibodies and placental functions. During nursing, the immune system of newborns is challenged with multiple milk-derived proteins. Amongst them, caseins are the main constituent. In particular, human αS1-casein (CSN1S1 was recently shown to possess immunomodulatory properties. We were thus interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood. METHODS: 62 sera of healthy adult individuals who were (n = 37 or were not (n = 25 breast-fed against human CSN1S1 were investigated by a new SD (surface display-ELISA. For cross-checking, these sera were tested for anti Epstein-Barr virus (EBV antibodies by a commercial ELISA. RESULTS: IgG-antibodies were predominantly detected in individuals who had been nursed. At a cut-off value of 0.4, the SD-ELISA identified individuals with a history of having been breast-fed with a sensitivity of 80% and a specificity of 92%. Under these conditions, 35 out of 37 sera from healthy donors, who where breast-fed, reacted positively but only 5 sera of the 25 donors who were not breast-fed. The duration of breast-feeding was of no consequence to the antibody reaction as some healthy donors were only short term breast-fed (5 days minimum until 6 weeks maximum, but exhibited significant serum reaction against human CSN1S1 nonetheless. CONCLUSION: We postulate that human CSN1S1 is an autoantigen. The antigenicity is orally determined, caused by breast-feeding, and sustained into adulthood.

  15. Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

    Science.gov (United States)

    Mujtaba, Muhammad Ahmad; Fridell, Jonathan; Book, Benita; Faiz, Sara; Sharfuddin, Asif; Wiebke, Eric; Rigby, Mark; Taber, Tim

    2015-11-01

    Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.

  16. Nested N-terminal megalin fragments induce high-titer autoantibody and attenuated Heymann nephritis.

    Science.gov (United States)

    Tramontano, Alfonso; Knight, Thomas; Vizzuso, Domenica; Makker, Sudesh P

    2006-07-01

    It was shown previously that an N-terminal fragment (nM60) that encompasses amino acid residues 1 to 563 of megalin could induce active Heymann nephritis (AHN) as efficiently as the native protein. For delineation of a minimal structure within this fragment that is sufficient to induce AHN, smaller protein fragments that encompass residues 1 to 236 (L6), 1 to 195 (L5), 1 to 156 (L4), and 1 to 120 (L3), representing successive C-terminal truncations within ligand-binding repeats of nM60, were cloned and produced in a baculovirus insect cell expression system. Protein fragments L4, L5, and L6 clearly were glycosylated. All four fragments stimulated proliferation of megalin-sensitized lymph node cells and induced high-titer anti-megalin autoantibodies in Lewis rats. A full-blown disease, as assessed by severity of proteinuria, was observed in rats that were immunized with L6 and L5, whereas animals that were immunized with L4 and L3 developed only mild disease. The proteinuria levels correlated with staining for complement (C3, C5b-9) and IgG1 isotype in glomerular immune deposits. The results suggest that one or more molecular determinants on the region that comprises amino acid residues 157 to 236 contribute to the induction of a full-blown form of AHN. Study of the structure, conformation, and posttranslational modifications of these determinants could provide greater insight into the molecular correlates of immunopathogenesis in this disease model.

  17. 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.

  18. Detection of tumor-specific autoantibodies in sera of patients with lung cancer.

    Science.gov (United States)

    Nagashio, Ryo; Sato, Yuichi; Jiang, Shi-Xu; Ryuge, Shinichiro; Kodera, Yoshio; Maeda, Tadakazu; Nakajima, Takashi

    2008-12-01

    The presence of autoantibodies (AAs) in sera from two pulmonary carcinoma patients, adenocarcinoma (AD) and small cell carcinoma (SCLC) was screened by immunoblotting using cell lysate of four cell lines (LCN1, large cell neuroendocrine carcinoma (LCNEC); N231, SCLC; A549, AD; RERF-LC-AI, squamous cell carcinoma (SCC)). To identify the antigens recognized by AAs, two-dimensional gel electrophoresis was immunoblotted and target spots were cut out from the membrane and gel. After trypsin digestion, the proteins were analyzed by mass-spectrometry using a liquid chromatography-tandem mass spectrometer. By this method, cytokeratin18 (CK18) and villin1 were identified with AAs in sera from patients with AD and SCLC, respectively. Thus, the expressions of CK18 and villin1 were further immunohistochemically studied on 124 formalin-fixed and paraffin-embedded pulmonary carcinomas of various histologic types (44 AD, 27 SCC, 29 SCLC, and 34 LCNEC) using commercially available CK18 and villin1 antibodies. Positive CK18 immunostaining was observed in almost all cases with staining intensities significantly higher in AD and LCNEC than in SCC and SCLC. Villin1 was detected in 17/44 (38.6%) of AD and 21/34 (61.8%) of LCNEC, respectively, while in only one each of SCLC and SCC. Thus, villin1 and CK18 may be useful markers to distinguish LCNEC/AD from SCLC/SCC, and the present method might be useful to identify specific tumor-associated molecules in sera from pulmonary carcinoma patients with different histologic types.

  19. Relationship between antithyroglobulin autoantibodies and thyroglobulin recovery rates using different thyroglobulin concentrations in the recovery buffer.

    Science.gov (United States)

    Verburg, F A; Hartmann, D; Grelle, I; Giovanella, L; Buck, A K; Reiners, C

    2013-09-01

    The aim of the work was to examine the relationship between thyroglobulin autoantibody (TgAb) levels and the Tg recovery rate (TgRR) using different concentrations of Tg (50, 10, 5, and 1 μg/l) in the recovery buffer. A total number of 225 serum samples from individual patients were analyzed. Samples were selected for their TgAb in 6 groups: TgAb1 000 IU/ml (n=28). TgAb were measured with 2 different assays (VARELISA and BRAHMS Anti-Tgn RIA). TgAb levels and the TgRR determined using the 50, 10, 5, and 1 µg/l buffers showed strong significant correlations with a Spearmans' rho of - 0.720, - 0.688, - 0.686, and - 0.356, respectively, for the VARELISA assay and - 0.670, -0.617, - 0.570, and - 0.274, respectively, for the Anti-Tgn assay (all pbuffers with concentrations of 50, 10, 5, and 1 μg/l respectively. With decreasing Tg concentration in the recovery buffer the percentage of abnormal results increased, although the extreme increase we found in the 1 μg/l group is largely caused by a lack of analytical precision in the 73 sera with Tg levels exceeding 5 μg/l. Our results give cause for further investigation into reviving the concept of Tg-recovery measurement using 5 μg/l Tg in the recovery buffer instead of the traditional 50 μg/l.

  20. Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy.

    Science.gov (United States)

    Tomas, Nicola M; Hoxha, Elion; Reinicke, Anna T; Fester, Lars; Helmchen, Udo; Gerth, Jens; Bachmann, Friederike; Budde, Klemens; Koch-Nolte, Friedrich; Zahner, Gunther; Rune, Gabriele; Lambeau, Gerard; Meyer-Schwesinger, Catherine; Stahl, Rolf A K

    2016-07-01

    Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, and one-third of patients develop end-stage renal disease (ESRD). Circulating autoantibodies against the podocyte surface antigens phospholipase A2 receptor 1 (PLA2R1) and the recently identified thrombospondin type 1 domain-containing 7A (THSD7A) are assumed to cause the disease in the majority of patients. The pathogenicity of these antibodies, however, has not been directly proven. Here, we have reported the analysis and characterization of a male patient with THSD7A-associated MN who progressed to ESRD and subsequently underwent renal transplantation. MN rapidly recurred after transplantation. Enhanced staining for THSD7A was observed in the kidney allograft, and detectable anti-THSD7A antibodies were present in the serum before and after transplantation, suggesting that these antibodies induced a recurrence of MN in the renal transplant. In contrast to PLA2R1, THSD7A was expressed on both human and murine podocytes, enabling the evaluation of whether anti-THSD7A antibodies cause MN in mice. We demonstrated that human anti-THSD7A antibodies specifically bind to murine THSD7A on podocyte foot processes, induce proteinuria, and initiate a histopathological pattern that is typical of MN. Furthermore, anti-THSD7A antibodies induced marked cytoskeletal rearrangement in primary murine glomerular epithelial cells as well as in human embryonic kidney 293 cells. Our findings support a causative role of anti-THSD7A antibodies in the development of MN.

  1. Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy.

    Science.gov (United States)

    Hoxha, Elion; Thiele, Ina; Zahner, Gunther; Panzer, Ulf; Harendza, Sigrid; Stahl, Rolf A K

    2014-06-01

    Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an uncertain clinical outcome. The characterization of the phospholipase A2 receptor (PLA2R) as the major target antigen in primary MN and the detection of circulating autoantibodies in these patients is a major advance in understanding this disease. To test whether PLA2R antibody levels reflect disease activity or clinical outcome, we performed a prospective multicenter study of 133 adult patients with primary MN and detectable serum PLA2R antibodies who had not received immunosuppressive therapy. Patients were followed ≤24 months. PLA2R antibody levels associated with clinical disease activity (proteinuria) in patients with immunosuppressive therapy (n=101) or supportive care (n=32). Within 3 months, immunosuppressive therapy led to a sustained 81% reduction in PLA2R antibody levels paralleled by a 39% reduction in proteinuria. Patients who experienced remission of proteinuria after 12 months had significantly lower PLA2R antibody levels at the time of study inclusion compared with patients with no remission. Patients with high PLA2R antibody levels achieved remission of proteinuria significantly later than patients with low PLA2R antibody levels. PLA2R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria. Multivariable Cox regression analysis confirmed PLA2R antibody level as an independent risk factor for not achieving remission of proteinuria. We conclude that a decrease in PLA2R antibody level is associated with a decrease of proteinuria in patients with primary MN.

  2. 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.

  3. 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.

  4. Autoantibodies against thrombospondin type 1 domain–containing 7A induce membranous nephropathy

    Science.gov (United States)

    Tomas, Nicola M.; Hoxha, Elion; Reinicke, Anna T.; Fester, Lars; Helmchen, Udo; Gerth, Jens; Bachmann, Friederike; Budde, Klemens; Zahner, Gunther; Rune, Gabriele; Lambeau, Gerard; Meyer-Schwesinger, Catherine

    2016-01-01

    Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, and one-third of patients develop end-stage renal disease (ESRD). Circulating autoantibodies against the podocyte surface antigens phospholipase A2 receptor 1 (PLA2R1) and the recently identified thrombospondin type 1 domain–containing 7A (THSD7A) are assumed to cause the disease in the majority of patients. The pathogenicity of these antibodies, however, has not been directly proven. Here, we have reported the analysis and characterization of a male patient with THSD7A-associated MN who progressed to ESRD and subsequently underwent renal transplantation. MN rapidly recurred after transplantation. Enhanced staining for THSD7A was observed in the kidney allograft, and detectable anti-THSD7A antibodies were present in the serum before and after transplantation, suggesting that these antibodies induced a recurrence of MN in the renal transplant. In contrast to PLA2R1, THSD7A was expressed on both human and murine podocytes, enabling the evaluation of whether anti-THSD7A antibodies cause MN in mice. We demonstrated that human anti-THSD7A antibodies specifically bind to murine THSD7A on podocyte foot processes, induce proteinuria, and initiate a histopathological pattern that is typical of MN. Furthermore, anti-THSD7A antibodies induced marked cytoskeletal rearrangement in primary murine glomerular epithelial cells as well as in human embryonic kidney 293 cells. Our findings support a causative role of anti-THSD7A antibodies in the development of MN. PMID:27214550

  5. ELISA subtypization of anti-ENA autoantibodies in clinical management of autoimmune diseases in Bosnia and Herzegovina.

    Science.gov (United States)

    Subasic, Djemo; Karamehic, Jasenko; Gavrankapetanovic, Faris; Hodzic, Harun; Kasumovic, Mersija; Delic-Sarac, Marina; Prljaca-Zecevic, Lamija

    2009-01-01

    The basis of autoimmune diseases such as SLE (Systemic Lupus Eritematodes), Sjogren's syndrome, scleroderma, dermatomyositis and polymiositis is the creation of auto-antibodies to the following specific extractable nuclear antigens (ENA):Jo-1, Ssl-70, SS-A, SS-B, Sm and Sm/RNPs. Some of these antigens are in fact enzymes (Jo-1-histidil-tRNA synthetase, Scl-70-topoisomerase) which are inhibited by specific autoantibodies--this leads to disturbance in the metabolism of DNA and protein biosynthesis. During 2009, we analyzed total of 87 serum samples of patients suspected for autoimmune disorder using ANA-IFA and ELISA-ENA-6 methods. After establishing IFA-ANA positivity (83.9%), all serum specimens; ANA positive and negative, were subtypized by ELISA ENA-6 test. Analysis showed the highest incidence of anti-SS-A (56%), and incidence of anti-SS-B (29.8%), anti-Sm/ RNP (11.5%), anti-Jo-1 (2.3%) and anti-Scl-70 (1,1%) auto-antibodies. Also, 78.5% of IFA-ANA negative serum specimens showed high level of positivity (212.50 and 277.0 IU/ml) to SS-A (78.5%) and SS-B (21.4%) antigenes using ELISA-ENA-6 subtypization. Following these results, we conclude that it is necessary to introduce Western blot confirmation testing. After comparing with other clinical findings, we diagnosed the following autoimmune diseases: SLE, Sjogren's syndrome and dermatomiosytis.

  6. Identification of 4-Trimethylaminobutyraldehyde Dehydrogenase (TMABA-DH as a Candidate Serum Autoantibody Target for Kawasaki Disease.

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    Atsuko Matsunaga

    Full Text Available Kawasaki disease (KD, an acute vasculitis that preferentially affects coronary arteries, is still the leading cause of acquired heart disease in children. Although the involvement of immune system malfunction in the onset of KD is suggested, its etiology still remains to be clarified. We investigated autoantibodies in KD patients, which are frequently found in sera from patients with autoimmune diseases, vasculitides and arteritides. We performed two-dimensional western blotting and LC-MS/MS to analyze the antigens of autoantibodies, detected two protein spots with 4 out of 24 sera from KD patients but not with 6 control sera, and identified the antigens as 4-trimethylaminobutyraldehyde dehydrogenase (TMABA-DH. A slot blot analysis with TMABA-DH as an antigen also revealed higher reactivities of patients' sera than control sera (positive rates: 18/43 vs 3/41. Using an enzyme-linked immunosorbent assay (ELISA, we found that the reactivity of anti-TMABA-DH antibodies in sera from KD patients was significantly higher than that in sera from age-matched controls. The optimal cut-off value of 0.043 had a sensitivity of 83.7% and a specificity of 80.0% in detecting KD patients (positive rates: 37/43 for KD patients, 9/41 for controls. Immunohistochemistry performed on thin sections of rat heart revealed that TMABA-DH colocalized with myosin light chains in cardiac myocytes. Patient sera with high reactivity gave similar immunostaining pattern. These results suggest that the detection of anti-TMABA-DH autoantibody could be a potential strategy for a diagnosis of KD.

  7. 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

  8. Zinc transporter 8 and its autoantibody%锌转运体8及其自身抗体

    Institute of Scientific and Technical Information of China (English)

    罗说明; 黄干; 周智广

    2009-01-01

    Zinc is an important component in the process of insulin synthesis, storage and secretion. Therefore beta cells need very efficient and special transporters to accumulate sufficient amounts of zinc in se-cretion vesicles. Recent studies suggest the zinc transporter eight (ZnT8) is a major autoantigen in type 1 di-abetes. It is a pancreatic beta-cell-specific zinc transporter,and plays an important role in the synthesis and secretion of insulin by affecting the concentration of zinc. ZnT8 autoantibodies are important for diagnosis and prediction in autoimmune diabetes, especially in subjects whose common autoantibodies are negative. The sin-gle nucleotide polymorphism of ZnT8 gene(SLC30A8)determines ZnT8 autoantibodies specificity.%锌是胰岛素储存和分泌机制中的一个重要组分,β细胞需要有效且特异的转运体来累积足够量的锌.锌转运体8(ZnT8)是新近发现的一种1型糖尿病自身抗原,具有高度β细胞特异性,通过影响锌离子浓度而在胰岛素合成和分泌中发挥重要作用.ZnT8自身抗体对自身免疫性糖尿病(尤其对其他自身抗体阴性者)有着重要的诊断与预测价值.ZnT8基因(SLC30A8基因)多态性影响ZnT8自身抗体的特异性.

  9. 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.

  10. Role of Structure-Based Changes due to Somatic Mutation in Highly Homologous DNA-Binding and DNA-Hydrolyzing Autoantibodies Exemplified by A23P Substitution in the VH Domain

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    A. V. Kozyr

    2012-01-01

    Full Text Available Anti-DNA autoantibodies are responsible for tissue injury in lupus. A subset of DNA-specific antibodies capable of DNA cleavage can be even more harmful after entering the living cells by destroying nuclear DNA. Origins of anti-DNA autoantibodies are not fully understood, and the mechanism of induction of DNA-cleaving activity remains speculative. The autoantibody BV04-01 derived from lupus-prone mouse is the only DNA-hydrolyzing immunoglobulin with known 3D structure. Identification and analysis of antibodies homologous to BV04-01 may help to understand molecular bases and origins of DNA-cleaving activity of autoantibodies. BLAST search identified murine anti-DNA autoantibody MRL-4 with sequences of variable region genes highly homologous to those of autoantibody BV04-01. Despite significant homology to BV04-01, not only MRL-4 had no DNA-cleaving activity, but also reversion of its unusual P23 mutation to the germline alanine resulted in a dramatic loss of affinity to DNA. Contrary to this effect, transfer of the P23 mutation to the BV04-01 has resulted in a significant drop in DNA binding and almost complete loss of catalytic activity. In the present paper we analyzed the properties of two homologous autoantibodies and mutants thereof and discussed the implications of unusual somatic mutations for the development of autoantibodies with DNA-binding and DNA-hydrolyzing activity.

  11. Non-muscle myosin as target antigen for human autoantibodies in patients with hepatitis C virus-associated chronic liver diseases.

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    von Mühlen, C A; Chan, E K; Peebles, C L; Imai, H; Kiyosawa, K; Tan, E M

    1995-04-01

    Three patients with hepatitis C virus (HCV)-related chronic liver disease were shown to have autoantibodies strongly reacting with cytoskeletal fibres of non-muscle cells. The heavy chain of non-muscle myosin microfilament was the main target for those autoantibodies, as determined by (i) cell and tissue immunofluorescence studies showing colocalization with an anti-myosin antibody prototype; (ii) primary reactivity in immunoblotting with a 200-kD protein, using either MOLT-4 cells, human platelets, or affinity-purified non-muscle myosin as antigen extract; and (iii) immunoblotting of similar immunoreactive fragments in papain-digested MOLT-4 cell extracts, by using those human sera and antibody prototype. Autoantibodies to non-muscle myosin heavy chain were not previously reported in patients with chronic liver diseases, especially in those associated with HCV infection.

  12. [Systemic lupus erythematosus between clinical practice and the laboratory: state of the art and new findings on anti-DNA autoantibodies].

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    Brusca, Ignazio; Corrao, Salvatore; Li Vigni, Piero; Sucato, Rosa; La Chiusa, Stella Maria

    2002-06-01

    Identification of autoantibodies directed against nuclear antigens is a very important finding in the assessment of autoimmune rheumatic diseases. In particular, the anti-DNA autoantibodies have assumed a fundamental importance, both speculative and clinical, in the study of the systemic lupus erythemathous. The aim of the present review is to focalize on anti-DNA the mechanisms of both induction and production of anti-DNA autoantibodies, pathophysiologic and diagnostic and clinical aspects. For this purpose, forty years of studies on this topic have been reviewed. Aspects on different conformational shapes of double-stranded DNA have been discussed such as related pathogenetic and diagnostic ones. Finally, the review has dealt with experimental therapies, focusing on both animal models and the most recent clinical trials according to Evidence Based Medicine.

  13. [Monoclonal autoantibodies to the epithelial basement membrane cells of human skin and thymus obtained through immunization with Rickettsia prowazekii antigens].

    Science.gov (United States)

    Drobyshevskaia, E I; Spitsyn, S V; Nedialkov, Iu A; Shchekotikhina, Iu A; Tarasevich, I V

    1989-05-01

    As the result of immunization of BALB/c mice with the commercial preparation of typhus vaccine and R. prowazekii corpuscular antigen, in 29.2% and 40.3% of cases (respectively) the appearance of hybridomas synthesizing monoclonal antibodies (McAb) to different autologous structures (skin and thymic epithelium, cell nuclei, conjunctive tissue structures and vascular endothelium) has been revealed. The McAb under test have proved to be IgM-autoantibodies. McAb M-6, active against the basal membrane of human skin and thymic epithelium, produce quite a definite picture of disturbances in the differentiation of epithelium and can be used for the diagnosis of dyskeratosis.

  14. Steroid-responsive thalamic lesions accompanying microbleeds in a case of Hashimoto's encephalopathy with autoantibodies against α-enolase.

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    Yamaguchi, Yoshitaka; Wada, Manabu; Tanji, Haruko; Kurokawa, Katsuro; Kawanami, Toru; Tanji, Kazuyo; Yoneda, Makoto; Kato, Takeo

    2013-01-01

    A 67-year-old man receiving antithrombotic therapy developed rapidly progressive amnesia. T2-weighted images of brain MRI revealed hyperintense lesions in the bilateral thalami accompanied by microbleeds. Antithyroglobulin antibodies and autoantibodies against the N-terminal of α-enolase (NAE) were identified in the patient's serum; therefore, Hashimoto's encephalopathy (HE) was suspected. Although the patient's radiological findings improved following steroid therapy, his symptoms did not improve, possibly due to increased thalamic microbleeds. Because anti-NAE antibodies are possibly associated with vasculitis, HE accompanied by anti-NAE antibodies may be exacerbated by microbleeds in patients receiving antithrombotic therapy.

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

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    Dong Jun

    2010-09-01

    Full Text Available 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 CDC25B-Abs in patients with ESCC. Methods CDC25B autoantibodies were measured in sera from both 134 patients with primary ESCC and 134 healthy controls using a reverse capture enzyme-linked immunosorbent assay (ELISA in which anti-CDC25B antibodies bound CDC25B antigen purified from Eca-109 ESCC tumor cells. The clinicopathologic significance of CDC25B serum autoantibodies was compared to that of the tumor markers carcinoembryonic antigen (CEA, squamous cell carcinoma antigen (SCC-Ag and cytokeratin 19 fragment antigen 21-1(CYFRA21-1. Results Higher levels of CDC25B autoantibodies were present in sera from patients with ESCC (A450 = 0.917, SD = 0.473 than in sera from healthy control subjects (A450 = 0.378, SD = 0.262, P 450 greater than the cut-off value of 0.725. Relatively few patients tested positive for the tumor markers CEA, SCC-Ag and CYFRA21-1 (13.4%, 17.2%, and 32.1%, respectively. A significantly higher number of patients with ESCC tested positive for a combination of CEA, SCC, CYFRA21-1 and CDC25B-Abs (64.2% than for a combination of CEA, SCC-Ag and CYFRA21-1 (41.0%, P P P = 0.001, log-rank. In the N1 subgroup, the cumulative five-year survival rate of CDC25B-seropositive patients was 13.6%, while that of CDC25B-seronegative patients was 54.5% (P = 0.040, log-rank. Conclusions Detection of serum CDC25B-Abs is superior to detection of the tumor markers CEA, SCC-Ag and CYFRA21-1 for diagnosis of ESCC, and CDC25B-Abs are a potential prognostic

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

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    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.

  17. A Case of Dermatomyositis and Anti-EJ Autoantibody with Chronic Intestinal Pseudoobstruction Successfully Treated with Octreotide

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    Chiho Yamada

    2016-01-01

    Full Text Available Chronic intestinal pseudoobstruction (CIPO is a serious complication in patients with connective tissue disease (CTD and is sometimes life-threatening or fatal despite intensive medical treatment. Here, we report a patient with dermatomyositis (DM and anti-EJ autoantibody who developed CIPO that was improved by octreotide. Because her abdominal pain and bloatedness were so severe and persistent, we introduced octreotide to relieve symptoms. In this case, continuous intravenous administration as well as long-acting subcutaneous injection of octreotide was effective for treating CIPO.

  18. Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro

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    Svegliati, Silvia; Amico, Donatella; Spadoni, Tatiana; Fischetti, Colomba; Finke, Doreen; Moroncini, Gianluca; Paolini, Chiara; Tonnini, Cecilia; Grieco, Antonella; Rovinelli, Marina; Gabrielli, Armando

    2017-01-01

    One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration, and type I collagen gene α1 chain expression) and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti-PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms, and mammalian target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen α1 chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smooth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species and expression of NOX4 and mTORC1. Our data indicate that agonistic anti-PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia. PMID:28228756

  19. Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

    Science.gov (United States)

    Savolainen, Markku J.

    2016-01-01

    Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p = 0.001), and 76.1 (48.2) for NoDR (p = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p > 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.

  20. Vitamin D deficiency as a risk factor for the development of autoantibodies in patients with ASIA and silicone breast implants: a cohort study and review of the literature.

    Science.gov (United States)

    Colaris, Maartje J L; van der Hulst, Rene R; Tervaert, Jan Willem Cohen

    2017-03-17

    The development of autoimmunity and/or autoimmune diseases is multifactorial. Vitamin D is one of the factors that might play a role. We postulated that both the presence of adjuvants and insufficient levels of vitamin D may result in the development of autoimmunity in patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in relation to silicone implant incompatibility. We measured vitamin D levels in 135 patients with ASIA in relation to silicone implant incompatibility and related findings to the presence of autoantibodies that are commonly used to diagnose systemic autoimmune diseases. Furthermore, we systematically reviewed the literature regarding vitamin D deficiency as a risk factor for the development of autoantibodies. Vitamin D measurements were available for analysis in 131 of 135 patients with ASIA in relation to SIIS. Twenty-three patients (18%) tested positive for autoantibodies, from which 18 patients (78%) had either a vitamin D deficiency or insufficiency (median vitamin D level 60.5 mmol/L), whereas five patients (22%) had sufficient vitamin D levels. The risk to develop autoantibodies was significantly increased in vitamin D deficient and/or insufficient patients [RR 3.14; 95% CI, 1.24-7.95; p = 0.009]. Reviewed literature suggested an association between vitamin D levels and the presence and/or titer levels of autoantibodies in different autoimmune diseases. From our current study and from our review of the literature, we conclude that vitamin D deficiency is related to the presence of autoantibodies. Whether vitamin D supplementation results in a decrease of autoimmunity needs to be studied prospectively.

  1. Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells.

    Science.gov (United States)

    Weinstein, Jason S; Delano, Matthew J; Xu, Yuan; Kelly-Scumpia, Kindra M; Nacionales, Dina C; Li, Yi; Lee, Pui Y; Scumpia, Philip O; Yang, Lijun; Sobel, Eric; Moldawer, Lyle L; Reeves, Westley H

    2013-04-15

    Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (lipogranuloma) formation. A novel transplantation model was used to show that transplanted lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4(+) T cells were not required for autoantibody production from the transplanted lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell-dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.

  2. 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.

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

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    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.

  4. Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease.

    Science.gov (United States)

    Alexopoulos, Harry; Kampylafka, Eleni I; Fouka, Penelope; Tatouli, Ioanna; Akrivou, Sofia; Politis, Panagiotis K; Moutsopoulos, Haralampos M; Tzioufas, Athanasios G; Dalakas, Marinos C

    2015-12-15

    Anti-aquaporin-4 autoantibodies are specific for the neuromyelitis optica spectrum disorders (NMOSD) and they have also been described in patients with systemic lupus erythematosus (SLE) with neurological signs consistent with NMOSD. Our objective was to test for the presence and pathogenicity of anti-AQP4 antibodies in SLE patients without neurological disease. Sera from 89 non-CNS-SLE patients were screened for anti-AQP4 autoantibodies. Two of the 89 patients were positive. Archived samples dating back 11 years were also positive. A brain and spinal cord MRI did not reveal any NMOSD-compatible lesions. An in vitro cytotoxicity assay showed that either sera or purified IgG from these patients induced a complement-mediated damage in cultured astrocytes comparable to antibodies obtained from typical NMO patients. We conclude that AQP4-antibodies can be present in SLE patients and persist for many years, without concurrent clinical or radiological NMOSD signs. It is unclear why the anti-AQP4 antibodies did not induce CNS disease.

  5. Anti-Platelet and Anti-Endothelial Cell Autoantibodies in Vietnamese Infants and Children with Dengue Hemorrhagic Fever

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    Nguyen Thanh Hung

    2008-01-01

    Full Text Available Dengue hemorrhagic fever (DHF is a serious public health problem. Increased vascular permeaxbility and thrombocytopenia are the hallmarks of DHF. The mechanisms involved in DHF/Dengue shock syndrome (DSS pathogenesis is not fully understood. This study gives evidence of the presence of antibodies which cross-reacted with platelets, and endothelial cells in the sera of Vietnamese infants and children with DHF/DSS. The anti-platelet, anti-endothelial cell IgM levels were higher in the sera of DHF/DSS infants and children, compared with controls. However, the levels of these autoantibodies were not correlated with the severity of DHF (non-shock DHF vs DSS. The anti-platelet, and anti-endothelial cell autoantibodies may play a role in the pathogenesis of DHF/DSS in infants and children with predominantly primary, and secondary dengue infections, respectively. The epitopes shared by surface molecules of platelets and endothelial cells and dengue virus antigens need to be identified and avoided in designing the safe candidate vaccines.

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

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    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.

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

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    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.

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

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    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.

  9. 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.

  10. 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.

  11. [Islet autoantibody assays in type I diabetes: superiority of passage from use of ICA to traditional tests].

    Science.gov (United States)

    Lazar, D; Weintrob, N; Abramov, N; Assa, S; Bloch, K; Ofan, R; Ben-Zaken, H; Vardi, P

    1998-05-01

    Islet cell antibodies (ICA) continue to serve as the basis of the principal serological test for definition of active autoimmunity of beta-cells. Its disadvantages are the need for human pancreatic tissue and difficulty in obtaining quantitative results. In the past decade biochemically-defined beta-cell antigens were described, leading to the development of sensitive and specific autoantibody assays, to predict insulin-dependent diabetes mellitus (IDDM). We examined the value of combined biochemically-based serological assays, such as autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and ICA512 (ICA512A) to replace the traditional ICA assay. Blood samples of 114 newly diagnosed IDDM patients, aged 12 +/- 5 yrs (range 2 months-29 years) were tested for ICA (indirect immunofluorescence), IAA, GADA and ICA512A (radiobinding assay). The latter 2 assays were performed using recombinant human [35S]-labeled antigen produced by in vitro transcription/translation. We found that fewer sera scored positive for ICA and/or IAA (80.7%, 92/114) than for 1 or more of IAA, GAD, or ICA512 (88.6%, 101/114). We conclude that combined testing for IAA, GAD and ICA512 can replace the traditional ICA/IAA test to predict IDDM and is helpful in the differential diagnosis of insulin-dependent and noninsulin-dependent diabetes.

  12. Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

    Institute of Scientific and Technical Information of China (English)

    Theodoros A Zografos; Nikolaos Gatselis; Kalliopi Zachou; Christos Liaskos; Stella Gabeta; George K Koukoulis; George N Dalekos

    2012-01-01

    AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients.METHODS:The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays,dot-blot assays,and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients.In order to specify our results,the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asy.mptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely,autoimmune hepatitis-1 or primary sclerosing cholangitJs (AIH-1/PSC).RESULTS:AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls.The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%,95% confidence interval (CI):12%-28.1% vs 2.5%,95% CI:0.1%-14.7%,P =0.01; 18.8%,95% CI:12%-28.1% vs 0%,95% CI:0%-10.9%,P =0.003,respectively].PBC-specific ANA positivity was observed in only one FDR from a PSC patient.Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio:11.24,95% CI:1.27-25.34,P =0.03) whereas among the investigated comorbidities and risk factors,a positive past history for urinary tract infections (UTI)was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92,95% CI:1.25-12.35,P =0.02).CONCLUSION:In FDRs of Greek PBC patients,AMA prevalence is significantly increased and independently associated with past UTI.PBC-specific ANA were not detected in anyone of PBC FDRs.

  13. Cross-Reaction of SARS-CoV Antigen with Autoantibodies in Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Yunshan Wang; Nongjian Guo; Tanghong Jia; Shanhui Sun; Hong Shen; Lihua Jiang; Maoxiu Zhang; Dongjie Xiao; Yang Liu; Xiaoli Ma; Yong Zhang

    2004-01-01

    To investigate the significance of the SARS-associated coronavirus (SARS-CoV) antibody, detected by ELISA and indirect immunofluorescence assays (IFA) for the SARS-CoV Vero E6 cell lysates, in non-SARS subjects,114 serum samples from healthy controls and 104 serum specimens from autoimmune disease patients were collected. The results of ELISA showed that among 114 sera from healthy controls, 4 (3.5 %) were positive of SARS-CoV-IgG antibody and 114 (100%) were all negative of SARS-CoV-IgM antibody; the specificity of SARS-CoV-IgG antibody for SARS patients was 96.5%, but the specificity of both SARS-CoV-IgG and -IgM antibodies for SARS patients was 100%. In 58 cases with SLE, positive rates of SARS-CoV-IgG and -IgM antibodies were 32.8% (19/58) and 8.6% (5/58), respectively, in which 11 cases (19%) were positive of both SARS-CoV-IgG and -IgM antibodies; in 10 cases with SS, positive rate of both SARS-CoV-IgG and -IgM antibodies was 10% (1/10); in 16 cases with MCTD, positive rate of SARS-CoV-IgG was 37.5% (6/16), positive rate of both SARS-CoV-IgG and -IgM antibodies was 6.3% (1/16); in 20 cases with RA, one case was positive (5%) of SARS-CoV-IgG. However, of all samples with positive SARS-CoV-IgG and -IgM antibodies for autoimmune diseases and healthy controls, SARS-CoV RNA and antibodies were all negative by RT-PCR and IFA. All sera for negative or positive ELISA results were also negative or positive results using ELISA with Vero E6 cells lysates. These studies showed that SARS-CoV Vero E6 cell lysates for the ELISA to detect SARS-CoV antibodies could lead to the false-positive reactions or cross-reactions of SARS-CoV antibodies in non-SARS diseases and healthy controls, and the false-positive reactions or cross-reactions were related to Vero E6 cell lysates and autoantibodies in non-SARS population.

  14. Cross-Reaction of SARS-CoV Antigen with Autoantibodies in Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    YunshanWang; ShanhuiSun; HongShen; LihuaJiang; MaoxiuZhang; DongjieXiao; YangLiu; XiaoliMa; YongZhang; NongjianGuo; TanghongJia

    2004-01-01

    To investigate the significance of the SARS-associated coronavirus (SARS-CoV) antibody, detected by ELISA and indirect immunofluorescence assays (IFA) for the SARS-CoV Vero E6 cell lysates, in non-SARS subjects, 114 serum samples from healthy controls and 104 serum specimens from autoimmune disease patients were collected. The results of ELISA showed that among 114 sera from healthy controls, 4 (3.5%) were positive of SARS-CoV-IgG antibody and 114 (100%) were all negative of SARS-CoV-IgM antibody; the specificity of SARS-CoV-IgG antibody for SARS patients was 96.5%, but the specificity of both SARS-CoV-IgG and -IgM antibodies for SARS patients was 100%. In 58 cases with SLE, positive rates of SARS-CoV-IgG and -IgM antibodies were 32.8% (19/58) and 8.6% (5/58), respectively, in which 11 cases (19%) were positive of both SARS-CoV-IgG and -IgM antibodies; in 10 cases with SS, positive rate of both SARS-CoV-IgG and -IgM antibodies was 10% (1/10); in 16 cases with MCTD, positive rate of SARS-CoV-IgG was 37.5% (6/16), positive rate of both SARS-CoV-IgG and -IgM antibodies was 6.3% (1/16); in 20 cases with RA, one case was positive (5%) of SARS-CoV-IgC However, of all samples with positive SARS-CoV-IgG and -IgM antibodies for autoimmune diseases and healthy controls, SARS-CoV RNA and antibodies were all negative by RT-PCR and IFA. All sera for negative or positive ELISA results were also negative or positive results using ELISA with Vero E6 cells lysates. These studies showed that SARS-CoV Vero E6 cell lysates for the ELISA to detect SARS-CoV antibodies could lead to the false-positive reactions or cross-reactions of SARS-CoV antibodies in non-SARS diseases and healthy controls, and the false-positive reactions or cross-reactions were related to Vero E6 cell lysates and autoantibodies in non-SARS population. Cellular & Molecular Immunology.

  15. Auto-antibodies to double-stranded DNA as biomarker in systemic lupus erythematosus : comparison of different assays during quiescent and active disease

    NARCIS (Netherlands)

    de Leeuw, Karina; Bungener, Laura; Roozendaal, Caroline; Bootsma, Hendrika; Stegeman, Coen A

    2017-01-01

    OBJECTIVE: Auto-antibodies directed to dsDNA (anti-dsDNA) are used in diagnosis and follow-up for SLE. However, multiple assays are used. The objective of this study was to determine the best-performing assays, especially in prediction of exacerbations. METHODS: Seven assays were compared during LN

  16. No Contribution of GAD-65 and IA-2 Autoantibodies around Time of Diagnosis to the Increasing Incidence of Juvenile Type 1 Diabetes: A 9-Year Nationwide Danish Study

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    Steffen U. Thorsen

    2016-01-01

    Full Text Available Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65 (GADA and insulinoma associated antigen-2A (IA-2A mirrored the 3.4% annual increase in incidence of T1D. Methods. From the Danish Childhood Diabetes Register, we randomly selected 500 patients and 500 siblings for GADA and IA-2A analysis (1997 through 2005. Blood samples were taken within three months after onset. A robust log-normal regression model was used. Nine hundred children and adolescents had complete records and were included in the analysis. Cochran-Armitage test for trend was used to evaluate changes in prevalence of autoantibody positivity by period. Results. No significant changes in levels of GADA and IA-2A were found over our 9-year study period. No trends in autoantibody positivity—in either patients or siblings—were found. Levels of GADA and IA-2A were significantly associated with HLA risk groups and GADA with age. Conclusion. The prevalence of positivity and the levels of GADA and IA-2A have not changed between 1997 and 2005 in newly diagnosed patients with T1D and their siblings without T1D.

  17. Mimotopes for lupus-derived anti-DNA and nucleosome-specific autoantibodies selected from random peptide phage display libraries: facts and follies.

    NARCIS (Netherlands)

    Dieker, J.W.C.; Sun, Y.J.; Jacobs, C.W.M.; Putterman, C.; Monestier, M.; Muller, S.; Vlag, J. van der; Berden, J.H.M.

    2005-01-01

    Autoantibodies against chromatin are the most characteristic serological feature in SLE patients. Anti-dsDNA and nucleosome-specific antibodies are associated with glomerulonephritis, the most serious manifestation of SLE. Identification of peptides mimicking conformational epitopes (so-called mimot

  18. 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...

  19. 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

    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...

  20. Peptide-based ELISAs are not sensitive and specific enough to detect muscarinic receptor type 3 autoantibodies in serum from patients with Sjogren's syndrome

    NARCIS (Netherlands)

    Roescher, N.; Kingman, A.; Shirota, Y.; Chiorini, J.A.; Illei, G.G.

    2011-01-01

    Objectives The detection of autoantibodies to the muscarinic receptor type 3 (M3R) in the serum of patients with Sjogrens syndrome (SS) by ELISA is controversial. A study was undertaken to test whether modification of M3R peptides could enhance the antigenicity and increase the detection of specific

  1. 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.

  2. 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

  3. Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

    Science.gov (United States)

    Olivry, T; Chan, L S; Xu, L; Chace, P; Dunston, S M; Fahey, M; Marinkovich, M P

    1999-07-01

    In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

  4. Congenital heart block: identification of autoantibody binding site on the extracellular loop (domain I, S5-S6) of alpha(1D) L-type Ca channel.

    Science.gov (United States)

    Karnabi, Eddy; Qu, Yongxia; Wadgaonkar, Raj; Mancarella, Salvatore; Yue, Yuankun; Chahine, Mohamed; Clancy, Robert M; Buyon, Jill P; Boutjdir, Mohamed

    2010-03-01

    Congenital heart block (CHB) is an autoimmune disease associated with autoantibodies against intracellular ribonucleoproteins SSB/La and SSA/Ro. The hallmark of CHB is complete atrioventricular block. We have recently established that anti-SSA/Ro -SSB/La autoantibodies inhibit alpha(1D) L-type Ca current, I(Ca-L), and cross-react with the alpha(1D) Ca channel protein. This study aims at identifying the possible binding sites on alpha(1D) protein for autoantibodies from sera of mothers with CHB children. GST fusion proteins of the extracellular regions between the transmembrane segments (S5-S6) of each of the four alpha(1D) Ca channel protein domains I-IV were prepared and tested for reactivity with sera from mothers with CHB children and controls using ELISA. Sera containing anti-Ro/La autoantibodies from 118 mothers with CHB children and from 15 mothers with anti-Ro/La autoantibodies but have healthy children, and from 28 healthy mothers without anti-Ro/La autoantibodies and healthy children were evaluated. Seventeen of 118 (14.4%) sera from mothers with CHB children reacted with the extracellular loop of domain I S5-S6 region (E1). In contrast, only 2 of 28 (7%) of sera from healthy mothers (-anti-Ro/La) and healthy children reacted with E1 loop and none (0 of 15) of sera from healthy mothers (+anti-Ro/La) and healthy children reacted with the E1 loop. Preincubation of E1 loop with the positive sera decreased the O.D reading establishing the specificity of the response. Electrophysiological characterization of the ELISA positive sera and purified IgG showed inhibition (44.1% and 49.8%, respectively) of the alpha(1D) I(Ca-L) expressed in tsA201 cells. The inhibition was abolished when the sera were pre-incubated with E1 fusion protein. The results identified the extracellular loop of domain I S5-S6 of L-type Ca channel alpha(1D) subunit as a target for autoantibodies from a subset of mothers with CHB children. This novel finding provides insights into the

  5. Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A-induced hepatitis.

    Science.gov (United States)

    Nakano, Toshiaki; Goto, Shigeru; Lai, Chia-Yun; Hsu, Li-Wen; Takaoka, Yuki; Kawamoto, Seiji; Chiang, Kuei-Chen; Shimada, Yayoi; Ohmori, Naoya; Goto, Takeshi; Sato, Shuji; Ono, Kazuhisa; Cheng, Yu-Fan; Chen, Chao-Long

    2010-04-01

    We previously demonstrated the immunosuppressive activity of anti-histone H1 autoantibody induced in experimental and clinical liver allograft tolerance. This study aimed to explore the immunological aspects of anti-histone H1 autoantibody in liver injury induced by concanavalin A (Con A). To establish a Con A-hepatitis model, 20 mg/kg Con A was intravenously injected into rats, after which liver function and histopathological analyses were performed. In this model, anti-histone H1 autoantibody was transiently induced in the sera during the natural recovery stage, 3-7 days after Con A injection. To evaluate the therapeutic significance of anti-histone H1 autoantibody, a polyclonal antibody against histone H1 was intraperitoneally injected immediately after Con A injection. We found that injection of anti-histone H1 antibody could reduce Con A-induced liver damage. Further mechanical analyses revealed that anti-histone H1 antibody altered the intracellular activation of mitogen-activated protein kinase, nuclear factor-kappaB and calcineurin via T-cell receptor signalling, suggesting that anti-histone H1 antibody may protect the liver from Con A-induced injury by inhibiting activation of effector T cells. These findings suggest that anti-histone H1 autoantibody may be a natural immune regulatory factor that protects inflamed livers suffering from autoimmune hepatitis and may lead to T-cell unresponsiveness through the selective regulation of mitogen-activated protein kinase/nuclear factor-kappaB and calcineurin signalling.

  6. Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes.

    Science.gov (United States)

    Zhao, Lue Ping; Alshiekh, Shehab; Zhao, Michael; Carlsson, Annelie; Larsson, Helena Elding; Forsander, Gun; Ivarsson, Sten A; Ludvigsson, Johnny; Kockum, Ingrid; Marcus, Claude; Persson, Martina; Samuelsson, Ulf; Örtqvist, Eva; Pyo, Chul-Woo; Nelson, Wyatt C; Geraghty, Daniel E; Lernmark, Åke

    2016-03-01

    The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next-generation sequencing (NGS) was used to determine all DRB alleles in consecutively diagnosed patients ages 1-18 years with islet autoantibody-positive type 1 diabetes (n = 970) and control subjects (n = 448). DRB3, DRB4, or DRB5 alleles were tested for an association with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A, and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (P = 10(-36)), yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk, but its association with DRB1*04:05:01 decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with NGS should prove useful to select participants for prevention or intervention trials.

  7. Identification and clinical significance of an elevated level of serum aminoacylase-1 autoantibody in patients with hepatitis B virus-related liver cirrhosis.

    Science.gov (United States)

    He, Xiaomin; Hong, Yu; Wang, Xiaomei; Zhang, Xiaohong; Long, Jiang; Li, Hai; Zhang, Bei; Chen, Suhong; Liu, Qiqi; Li, Hongyi; Wang, Xiaoming; Ou, Xiaojuan; Huang, Jian

    2016-11-01

    Chronic hepatitis B (CHB) is prevalent worldwide and can develop into liver cirrhosis and liver carcinoma. Early discrimination of liver cirrhosis from chronic hepatitis is critical for effective treatment and optimal prognosis. The aim of the present study was to assess the diagnostic value of a panel of cellular proteins that can be recognized by autoantibodies in patient serum for hepatitis B virus (HBV)‑related liver cirrhosis. Twenty‑two candidate autoantigens screened using a serum proteomics assay in our previous study were assessed retrospectively in 443 participants, comprising 89 patients with HBV‑related liver cirrhosis, 89 patients with CHB, and 265 healthy controls. The levels of autoantibodies against the candidate autoantigens were measured by protein microarrays containing the candidate antigen proteins. Receiver operating characteristic (ROC) curves were used to calculate the diagnostic accuracy. The present study determined that seven of the 22 candidate autoantibodies differed significantly in serum level between HBV‑related liver cirrhosis and CHB (P0.7. The seven autoantibodies recognized aminoacylase‑1 (ACY1), histidine triad nucleotide‑binding protein 1, insulin‑like growth factor 2 mRNA‑binding protein 2, heat shock 70 kDa protein 6, peroxiredoxin 3, apoptosis‑inducing factor and regucalcin. Among these, the ACY1 autoantibody had the highest value for discriminating HBV‑related liver cirrhosis from CHB, with an AUC value of 0.872 (95% confidence interval: 0.810‑0.934, PHBV‑related liver cirrhosis from CHB.

  8. Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice.

    Science.gov (United States)

    Kuroda, Yoshiki; Ono, Nobutaka; Akaogi, Jun; Nacionales, Dina C; Yamasaki, Yoshioki; Barker, Tolga T; Reeves, Westley H; Satoh, Minoru

    2006-02-01

    A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.

  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. 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...... and the enzyme's role as an autoantigen in celiac disease, we have addressed structural properties of TG2 in solution by using hydrogen/deuterium exchange monitored by mass spectrometry. We demonstrate that Ca(2+) binding, which is necessary for TG2 activity, induces structural changes in the catalytic core...... domain of the enzyme. Cysteine oxidation was found to abolish these changes, suggesting a mechanism whereby disulfide bond formation inactivates the enzyme. Further, by using TG2-specific human monoclonal antibodies generated from intestinal plasma cells of celiac disease patients, we observed...

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

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    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. A Prospective Investigation of Graves' Disease and Selenium: Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms

    DEFF Research Database (Denmark)

    Calissendorff, Jan; Mikulski, Emil; Larsen, Erik Huusfeldt

    2015-01-01

    Background: In Graves' thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added....... Objective: The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety. Methods: We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid......-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 µg Se...

  13. Autoantibody-mediated cytotoxicity in paediatric opsoclonus-myoclonus syndrome is dependent on ERK-1/2 phophorylation.

    Science.gov (United States)

    Fühlhuber, Verena; Bick, Sandra; Tschernatsch, Marlene; Dharmalingam, Backialakshmi; Kaps, Manfred; Preissner, Klaus T; Blaes, Franz

    2015-12-15

    Paediatric opsoclonus-myoclonus syndrome (OMS) is in 50% of the cases associated with a neuroblastoma as a paraneoplastic syndrome and is associated with surface-binding antibodies against cerebellar granular neurons (CGN). To evaluate possible pathogenic effects of these autoantibodies on CGN we examined their influence on the MAPKinase enzymes ERK-1/2 and p38 using flow cytometry and phospho-specific antibodies. OMS IgG but not IgG from neuroblastoma without OMS or healthy controls induced phosphorylation of ERK-1/2 in cerebellar granular neurons (pERK-1/2 was associated with an increased cytotoxicity of CGN, which could be blocked by ERK-1/2 pathway inhibitor U0126. We here show that IgG-mediated anti-neuronal cytotoxicity in OMS is mediated by ERK-1/2 phosphorylation in CGN.

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

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    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.

  15. Association between polyclonal B cell activation and the presence of autoantibodies in mice infected with Yersinia enterocolitica O:3

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    B.M.M. Medeiros

    1997-03-01

    Full Text Available Eight-week old conventional female Swiss mice were inoculated intravenously with Yersinia enterocolitica O:3. A second group of normal mice was used as control. Five mice from each group were bled by heart puncture and their spleens were removed for spleen cell collection on the 3rd, 5th, 7th, 10th, 14th and 21st day after infection. Immunoglobulin-secreting spleen cells were detected by the isotype-specific protein A plaque assay. Total immunoglobulin levels were determined in mouse serum by single radial immunodiffusion and the presence of autoantibodies was determined by ELISA. We observed a marked increase in the total number of cells secreting immunoglobulins of all isotypes as early as on the 3rd day post-infection and the peak of secretion occurred on the 7th day. At the peak of the immunoglobulin response, the total number of secreting cells was 19 times higher than that of control mice and most immunoglobulin-secreting cells were of the IgG2a isotype. On the 10th day post-infection, total serum immunoglobulin values were 2 times higher in infected animals when compared to the control group, and continued at this level up to the 21st day post-infection. Serum absorption with viable Y. enterocolitica cells had little effect on antibody levels detected by single radial immunodiffusion. Analysis of serum autoantibody levels revealed that Y. enterocolitica infection induced an increase of anti-myosin and anti-myelin immunoglobulins. The sera did not react with collagen. The present study demonstrates that Y. enterocolitica O:3 infection induces polyclonal activation of murine B cells which is correlated with the activation of some autoreactive lymphocyte clones

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

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    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. Patients with systemic lupus erythematosus have higher prevalence of thyroid autoantibodies: a systematic review and meta-analysis.

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    Xi-Feng Pan

    Full Text Available Thyroid autoimmunity is considered the most common type of organ-specific autoimmune disorder and can be associated with other autoimmune endocrine disorders or non-endocrine diseases. Systemic lupus erythematosus is a prototypical autoimmune disorder with multifactorial etiology. The pathogenesis and development of the disease may result from a loss of immune tolerance and the resulting synthesis of autoantibodies against nuclear antigens. Autoimmune factors may be common features of both thyroid autoimmunity and systemic lupus erythematosus, making it likely that both conditions may coexist within some patients.A number of studies have investigated whether an association between thyroid autoimmunity and systemic lupus erythematosus exists. However, the results of these studies have been inconsistent. Furthermore, most of these studies have had relatively small sample sizes, which have rendered them insufficiently powerful to determine whether there is an association between systemic lupus erythematosus and thyroid autoimmunity. The main objective of this meta-analysis is to provide reliable estimates of the extent of any association between thyroid autoimmunity and systemic lupus erythematosus by combining the primary data from all relevant studies. Literature databases were searched, including the Medline, Embase, Web of Science, Chinese Wanfang and CBM databases, from January 1970 to May 2014. A total of 1076 systemic lupus erythematosus cases and 1661 healthy controls were included in this study. From these data, the odds ratio (OR and the corresponding 95% confidence interval (95% CI were calculated. The meta-analysis results showed that the prevalence of thyroid autoantibody positivity in patients with systemic lupus erythematosus was higher than in healthy controls (TgAb: OR = 2.99, 95% CI = 1.83-4.89; TPOAb: OR = 2.20, 95% CI = 1.27-3.82, respectively.The results of this meta-analysis suggest that thyroid autoimmunity is more prevalent

  18. Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus

    Science.gov (United States)

    Clavarino, Giovanna; Jourde-Chiche, Noémie; Ouili, Saber; Paul, Stéphane; Gout, Evelyne; Sarrot-Reynauld, Françoise; Bardin, Nathalie; Boëlle, Pierre -Yves; Chiche, Laurent; Bouillet, Laurence; Thielens, Nicole M.; Cesbron, Jean-Yves; Dumestre-Pérard, Chantal

    2016-01-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients. PMID:27631981

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

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    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.

  20. A desmoplakin point mutation with enhanced keratin association ameliorates pemphigus vulgaris autoantibody-mediated loss of cell cohesion.

    Science.gov (United States)

    Dehner, Carina; Rötzer, Vera; Waschke, Jens; Spindler, Volker

    2014-09-01

    Desmoplakin (DP) serves to anchor intermediate filaments in desmosomal complexes. Recent data suggest that a specific DP point mutation (S2849G) exhibits increased keratin filament association and fosters Ca(2+) insensitivity of desmosomes in keratinocytes, presumably by rendering DP inaccessible for protein kinase C (PKC) phosphorylation. Previously, we have reported that depletion of the desmosomal adhesion molecule desmoglein (Dsg)3 induced by autoantibodies from patients with the blistering skin disease pemphigus vulgaris (PV) IgG is reduced in maturated desmosomes and dependent on PKC signaling. We investigated the role of DP-S2849G for loss of cell cohesion mediated by PV-IgG. In cell dissociation assays, expression of green fluorescent protein-tagged DP-S2849G (DP-S2849G-GFP) increased cell cohesion in two different human keratinocyte cell lines and ameliorated loss of cell adhesion induced by pemphigus autoantibodies. Depletion of Dsg3 was inhibited by DP-S2849G-GFP in the cytoskeletal (Triton X-100 insoluble) fraction, and keratin filament retraction, a hallmark of PV, was efficiently blocked similar to treatment with the PKC inhibitor Bim-X. We found that DP is phosphorylated after incubation with PV-IgG in a PKC-dependent manner and that DP-S2849G-GFP expression prevents DP phosphorylation and increases association of PKC-α with PKC scaffold receptor for activated C-kinase 1. Taken together, our data indicate that DP phosphorylation at S2849 represents an important mechanism in pemphigus pathogenesis, which, by reversing Ca(2+) insensitivity, promotes Dsg3 depletion.

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

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    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

  2. 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...... plasma samples and pooled normal immunoglobulin preparations were used to validate the assay. Plasma samples from 98 transfusion recipients, half of whom presented with febrile reactions, were tested by the assay. RESULTS: The assay detected specific and saturable immunoglobulin G (IgG) binding to each...... cytokine autoantibodies quantities in the negative plasma samples ranged between 80% and 125%. The analytical intra- and inter-assay variations were 4% and 11%, respectively. Varying c-aAb levels were detectable in the transfusion recipients. There was no difference in c-aAb frequency between the patients...

  3. 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

  4. Anti-Aβ Autoantibodies in Amyloid Related Imaging Abnormalities (ARIA): Candidate Biomarker for Immunotherapy in Alzheimer’s Disease and Cerebral Amyloid Angiopathy

    Science.gov (United States)

    DiFrancesco, Jacopo C.; Longoni, Martina; Piazza, Fabrizio

    2015-01-01

    Amyloid-related imaging abnormalities (ARIA) represent the major severe side effect of amyloid-beta (Aβ) immunotherapy for Alzheimer’s disease (AD). Early biomarkers of ARIA represent an important challenge to ensure safe and beneficial effects of immunotherapies, given that different promising clinical trials in prodromal and subjects at risk for AD are underway. The recent demonstration that cerebrospinal fluid (CSF) anti-Aβ autoantibodies play a key role in the development of the ARIA-like events characterizing cerebral amyloid angiopathy-related inflammation generated great interest in the field of immunotherapy. Herein, we critically review the growing body of evidence supporting the monitoring of CSF anti-Aβ autoantibody as a promising candidate biomarker for ARIA in clinical trials. PMID:26441825

  5. 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

    of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where...... women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after recruitment and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2 and 13.4% sensitivity, respectively......, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity...

  6. 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

    deposition, indicating that formation of complement-activating immune complexes played a role in the binding process. Furthermore, MBP elicited tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 production by normal mononuclear cells in the presence of serum from both patients and controls....... Mononuclear cells from MS patients responded to MBP with the production of interferon (IFN)-gamma, IL-4 and IL-5, in addition to TNF-alpha and IL-10. The production of IFN-gamma and IL-5 was increased when MS serum was added rather than normal serum. Denaturation of MBP strongly inhibited MBP deposition...... 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...

  7. [Detection of anti-ENA autoantibodies in patients with systemic connective tissue diseases. Analytical variability and diagnostic sensitivity of 4 methods].

    Science.gov (United States)

    Villalta, D; Bizzaro, N; Tonutti, E; Visentin, D; Manoni, F; Piazza, A; Toffolo, L; Rizzotti, P; Clemen, P; Pradella, M; Bassetti, D; Tozzoli, R

    1999-11-01

    This study was designed to assess the analytical sensitivity and rate of agreement between commercial methods and reagents, among the most used in Italy for the detection of autoantibodies to extractable nuclear antigens (ENA). Sixty-eight serum samples from patients with clinically diagnosed systemic rheumatic diseases were aliquoted and distributed to 4 hospital laboratories; three ELISA (Elias, Shield, Inova) and 1 immunoblot method (Euroimmun) were used. Overall agreement between the test reagents, for each anti-ENA specificity, was 69.1% for Ro/SSA, 83.3% for La/SSB, 70.6% for RNP, 73.5% for Sm, 91.1% for Jo1, and 82.3% for Scl70. Lack of specificity (i.e., false positive reactions) was the most important cause of low concordance. When the data were analysed according to the clinical diagnosis, total agreement and specificity improved. However, a significant difference in terms of sensitivity was observed in the SLE group (30 sera) for RNP (positivity ranged from 20% to 43%) and for Sm (from 7% to 37%), and in the Sjögren's syndrome group (13 sera) for anti-La/SSB (from 8% to 38%). Comparable data were obtained for anti-Ro/SSA (from 70% to 77%) both in the SLE and the Sjögren's syndrome group. Sensitivity of all 4 reagents was good in detecting anti-Scl70 autoantibodies in the 8 patients with diffuse systemic sclerosis, as well as anti-Jo1 autoantibody in the 5 polymyositis patients, with a 100% and a 95% agreement, respectively. These data suggest the need of a better standardization of commercial reagents and analytical procedures, and the opportunity that every laboratory should perform anti-ENA determination by at least two different methods, since none of the methods tested was completely reliable in detecting all anti-ENA autoantibody specificities.

  8. Impact analysis of autoantibody level and NR2 antibody level in neuropsychiatric SLE treated by methylprednisolone combined with MTX and DXM intrathecal injection.

    Science.gov (United States)

    Wang, Jingyuan; Zhao, Yinhuan; Zhang, Jihui; Lei, Hongwei; Zhu, Guiqi; Fu, Bingbing

    2014-11-01

    The objective is to explore the clinical curative effects of methylprednisolone combined with MTX and DXM intrathecal injection in treating neuropsychiatric systemic lupus erythematosus (NPSLE) and its effects on autoantibody level and anti-N-methyl-D-aspartate receptor subtype NR2a/2b antibody (anti-NR2 antibody) level. Thirty six admitted NPSLE patients were treated by methylprednisolone combined with MTX and DXM intrathecal injection. Thirty six SLE patients without neuropsychiatric symptoms were selected as non-NPSLE group. Clinical indexes including SLE activity index, erythrocyte sedimentation rate (ESR), cerebrospinal fluid pressure (CSFP), cerebrospinal fluid protein were observed before and after treatment. Autoantibodies including anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA antibody), anti-extractable nuclear antigen antibody (ENA-Ab) were detected before and after treatment. Enzyme linked immunosorbent assay was used to detect NR2 antibody level before and after treatment in two groups. Upon treatment of methylprednisolone combined with MTX and DXM intrathecal injection, SLE activity index, ESR, CSFP, cerebrospinal fluid protein of 36 NPSLE patients were significantly decreased. Before treatment, positive rates of ANA, anti-dsDNA antibody, and anti-ENA antibody in both NPSLE group and non-NPSLE group had no significant difference. However, positive rate of anti-NR2 antibody in NPSLE group was significantly higher than that of non-NPSLE group. After treatment, positive rates of autoantibodies and anti-NR2 antibody in both NPSLE and non-NPSLE group were significantly decreased. Anti-NR2 antibody can be a screening index of NPSLE, and methylprednisolone combined with MTX and DXM intrathecal injection has significant curative effects and can effectively decrease autoantibody level and anti-NR2 antibody level.

  9. 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.

  10. Islet autoantibodies in Latvian subjects with non-insulin-dependent diabetes mellitus: slow-onset type 1 diabetes or polyendocrine autoimmunity?

    Science.gov (United States)

    Shtauvere-Brameus, A; Falorni, A; Rumba, I; Sanjeevi, C B

    2002-04-01

    In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria; assays for the detection of autoantibodies are not available, and hence slowly progressive autoimmune diabetes is likely to be missed. Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. The aim of this study was to estimate the risk of polyendocrine autoimmunity among clinically diagnosed NIDDM patients from Latvia. One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. Age at onset was >or= 30 years, and duration of disease less than 5 years. Of 100 patients, 85 were on oral hypoglycemic agents and 15 were on insulin. Body mass index (BMI) under 19 was recorded in 1% (1 of 100 cases), while overweight (BMI > 25.5 in females and 27 in males) was documented in 45% (45 of 100 cases). GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). None of the patients carried antibodies against 21-OH and only 1 of 100 (1%) carried antibodies against TTG. From the results obtained in our study we conclude that in Latvian adult NIDDM subjects, islet autoantibodies identify groups of slow-onset type 1 diabetes but not polyendocrine autoimmunity.

  11. The presence of non-organ-specific autoantibodies is associated with a negative response to combination therapy with interferon and ribavirin for chronic hepatitis C

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    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.

  12. In a SLE mouse model the production of IgG autoantibody requires expression of activation-induced deaminase in early developing B cells

    Science.gov (United States)

    Umiker, Benjamin R.; McDonald, Gabrielle; Larbi, Amma; Medina, Carlos O.; Reth, Michael; Imanishi-Kari, Thereza

    2014-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of pathogenic IgG anti-nuclear antibodies. Pathogenic IgG autoantibody production requires B-cell activation, leading to the production of activation-induced deaminase (AID) and class switching of IgM genes to IgG. To understand how and when B cells are activated to produce these IgG autoantibodies, we studied cells from 564Igi, a mouse model of SLE. 564Igi mice develop a disease profile closely resembling that found in human SLE patients, including the presence of IgG anti-nucleic acid antibodies. We have generated 564Igi mice that conditionally express an activation-induced cytidine deaminase transgene (Aicdatg), either in all B cells or only in mature B cells. Here we show that class-switched pathogenic IgG autoantibodies were produced only in 564Igi mice in which AID was functional in early developing B cells, resulting in loss of tolerance. Furthermore, we show that the absence of AID in early developing B cells also results in increased production of self-reactive IgM, indicating that AID, through somatic hypermutation (SHM), contributes to tolerance. Our results suggest that the pathophysiology of clinical SLE might also be dependent on AID expression in early developing B cells. PMID:25044405

  13. Role of early glycation Amadori products of lysine-rich proteins in the production of autoantibodies in diabetes type 2 patients.

    Science.gov (United States)

    Ansari, Nadeem Ahmad; Moinuddin; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif; Khan, Rizwan Hasan

    2014-11-01

    In diabetes, protein glycation mostly occurs at intrachain lysine residues resulting in the formation of early stage Amadori products which are finally converted to advance glycation end products (AGEs). Several studies have reported autoantibodies against AGEs in diabetes but not much data are found in respect of Amadori products. In this study, poly-L-lysine (PLL) was glycated with 50 mM glucose and the resultant Amadori products were estimated by fructosamine or nitroblue tetrazolium assay. We report high content of Amadori products in PLL upon glycation. Glycated PLL showed marked hyperchromicity in the UV spectrum, ellipticity changes in CD spectroscopy, and variations in ε-methylene protons shift in NMR. It was better recognized by autoantibodies in type 2 diabetics compared to the native PLL. Induced antibodies against glycated PLL were successfully used to probe early glycation in the IgG isolated from diabetes type 2 patients. Role of Amadori products of glycated proteins in the induction of autoantibodies in type 2 diabetes as well as in associated secondary complications has been discussed.

  14. Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

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    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.

  15. Induction of ssDNA-binding autoantibody secreting B cell immunity during murine malaria infection is a critical part of the protective immune responses.

    Science.gov (United States)

    Mannoor, Kaiissar; Li, Changchun; Inafuku, Masashi; Taniguchi, Tomoyo; Abo, Toru; Sato, Yoshiya; Watanabe, Hisami

    2013-01-01

    Although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. In this study we demonstrate that the majority of anti-single stranded (ss) DNA autoantibody secreting B cells were confined to B220(+)CD21(+)CD23(-) cells and that these cells expanded significantly in the spleen of C57BL/6 mice infected with Plasmodium yoelii 17X non-lethal (PyNL). To determine the role of ssDNA-binding autoantibody secreting B cell responses in murine malaria, we conjugated generation 6 (poly) amidoamine dendrimer nanoparticles with ssDNA to deplete ssDNA-binding autoreactive B cells in vivo. Our data revealed that 55.5% of mice died after DNA-coated nanoparticle-mediated in vivo depletion of ssDNA-specific autoreactive B cells and subsequent challenge using PyNL. Adoptive transfer of B cells with ssDNA specificity to mice, followed by PyNL infection, caused a later appearance and inhibition of parasitemia. The possible mechanism by which the ssDNA-binding autoantibody secreting B cells is involved in the protection against murine malaria has also been demonstrated.

  16. In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway.

    Science.gov (United States)

    Lin, Yu-Ling; Tsai, Nu-Man; Hsieh, Cheng-Hao; Ho, Shu-Yi; Chang, Jung; Wu, Hsin-Yi; Hsu, Ming-Hua; Chang, Chia-Ching; Liao, Kuang-Wen; Jackson, Tiffany L B; Mold, David E; Huang, Ru Chih C

    2016-11-29

    Cancer progression is associated with the development of antitumor autoantibodies in patients' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan nordihydroguaiaretic acid (NDGA), enhanced the production of EAAs and inhibited tumor growth at low noncytotoxic concentrations via its immunoregulatory activity. Intratumoral injection of P4N improved the quantity and quality of EAAs, and passive transfer of P4N-induced EAAs dramatically suppressed lung metastasis formation and prolonged the survival of mice inoculated with metastatic CT26 tumor cells. P4N-induced EAAs specifically recognized two surface antigens, 78-kDa glucose-regulated protein (GRP78) and F1F0 ATP synthase, on the plasma membrane of cancer cells. Additionally, P4N treatment led to B-cell proliferation, differentiation to plasma cells, and high titers of autoantibody production. By serial induction of autocrine and paracrine signals in monocytes, P4N increased B-cell proliferation and antibody production via the leukotriene A4 hydrolase (LTA4H)/activin A/B-cell activating factor (BAFF) pathway. This mechanism provides a useful platform for studying and seeking a novel immunomodulator that can be applied in targeting therapy by improving the quantity and quality of the EAAs.

  17. [Laboratory-based evaluation of "INOVA/QUANTA Lite" to determine antinuclear antibodies (ANA) and autoantibodies to double-stranded DNA, SS-A and SS-B].

    Science.gov (United States)

    Yamauchi, Megumi S; Shingaki, Naohiko; Yamane, Nobuhisa

    2012-05-01

    We evaluated QUANTA Lite reagent series (INOVA Diagnostics, CA, USA) to determine antinuclear antibodies (ANA) and autoantibodies to double-stranded (ds) DNA, SS-A and SS-B, in parallel with MESACUP (Medical & Biological Laboratories, Nagoya). Overall agreements between two reagents for qualitative interpretation ranged from 77.5% (ANA) to 99.0%(anti-SS-B antibodies). When we compared to the results by indirect fluorescent antibody (IFA) test on HEp-2 cells, QUANTA Lite ANA demonstrated better sensitivity and specificity; 92.2% versus 76.5% in sensitivity and 92.1% versus 86.8% in specificity. Also, determining anti-chromatin antibodies and IFA test onto Chrithidia luciliae demonstrated greater interpretive correlation to detect anti-ds DNA by QUANTA Lite than by MESACUP. All the discrepant sera to which QUANTA Lite SS-A gave positive interpretations were confirmed to contain the antibodies specific to SS-A 52kDa antigen, which is supplemented to QUANTA Lite capture-probes. With these results, we can conclude that QUANTA Lite has superiorities over MESACUP; (1) to detect a variety of autoantibodies consisting of ANA, (2) to have a better correlation with confirmatory tests to detect anti-ds DNA antibodies, (3)to detect additional autoantibodies specific to SS-A 52kDa antigen, and (4) to have an enough compatibility in determining anti-SS-B antibodies.

  18. The development of a quantitative assay for the detection of anti-Ro/SS-A and anti-LA/SS-B autoantibodies using purified recombinant proteins.

    Science.gov (United States)

    Veldhoven, C H; Meilof, J F; Huisman, J G; Smeenk, R J

    1992-07-01

    A characteristic of patients with autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus is the presence of anti-Ro/SS-A and anti-La/SS-B autoantibodies in their circulation. In order to investigate specific autoantibody levels in the sera of these patients quantitative assays for the detection of both anti-Ro/SS-A and anti-La/SS-B reactivity were developed. Ro/SS-A (60 kDa) and La-SS-B (50 kDa) cDNAs were cloned and expressed in E. coli as non-fusion proteins. These were purified to homogeneity using two different purification protocols. With these recombinant antigens, specific enzyme-linked immunosorbent assays (ELISAs) were developed. 40 sera positive for anti-Ro/SS-A autoantibodies in counterimmunoelectrophoresis (CIE) were tested in both the Ro/SS-A and La/SS-B ELISA. Activity values reproducibly ranged from 1536 to 120,000 U in the Ro/SS-A ELISA and from 763 to 2,500,000 U in the La/SS-B ELISA. The suitability of these ELISAs as screening assays was further investigated by testing 200 sera sent to our laboratory for routine detection of autoantibodies to extractable nuclear antigen (ENA: anti-Sm, anti-RNP, anti-Ro/SS-A and anti-La/SS-B). Both ELISAs showed a high sensitivity and specificity (Ro/SS-A ELISA 85% and 94%, La/SS-B ELISA 100% and 98% respectively), when compared to the standard assays, the RNA-precipitation assay and the HeLa immunoblotting test. From these data we conclude that a quantitative analysis of both anti-Ro/SS-A and anti-La/SS-B autoantibodies is now possible using purified recombinant non-fusion proteins. For screening purposes the La/SS-B ELISA showed a great improvement in sensitivity for the detection of anti-La/SS-B activity in comparison to the La/SS-B CIE, while the Ro/SS-A ELISA almost equalled the performance of the Ro/SS-A CIE.

  19. Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

    Science.gov (United States)

    Lokant, M T; Naz, R K

    2015-04-01

    Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P prostatitis. All others were nonsignificant (P prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis.

  20. 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.

  1. The discrepancy between clinical and ultrasonographic remission in rheumatoid arthritis is not related to therapy or autoantibody status.

    Science.gov (United States)

    Spinella, Amelia; Sandri, Gilda; Carpenito, Giacomo; Belletti, Lorenza; Mascia, Maria Teresa

    2012-12-01

    To evaluate the clinical remission by means of power Doppler ultrasonographic (PDUS) monitoring in a group of patients with rheumatoid arthritis (RA) in clinical remission (DAS28 therapy with DMARDS, anti-TNF, or no therapy in clinical remission according to ACR criteria and DAS 28 inflammation in the past. US examination evaluated the presence of active synovitis, power Doppler signal, and synovial hypertrophy on the following bilateral joints: metacarpophalangeal-proximal interphalangeal joints-flexor tendons (on 2°-3° fingers) and wrist (radiocarpal and midcarpal joints). In 19 patients, there was an agreement between clinical and US parameters. However, 35 patients with clinical remission showed a positive ultrasonographic assessment and at least an active parameter. No statistic correlation was found between US examination and antibody assessment (anti-CCP and/or RF). Patients in therapy with anti-TNF or other therapies showed similar US assessment without significant statistical differences. Among eleven patients that presented swollen and tender joints at the latest physical examination, which preceded US exam, just 5 patients had an US confirmation too. In the other patients, the PDUS did not confirm the presence of inflammation in the corresponding swollen and tender joints or showed a positive ultrasonographic assessment in other locations. The remission state is a great therapy target and not only through the biological therapy. Synovial inflammation could persist independently from type of therapy or autoantibody status.

  2. Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis.

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    Arundhati Ray

    Full Text Available Inclusion body myositis (IBM belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG. These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens.

  3. Mini-Array of Multiple Tumor-Associated Antigens to Enhance Autoantibody Detection for Immunodiagnosis of Hepatocellular Carcinoma

    Science.gov (United States)

    Zhang, Jian-Ying

    2009-01-01

    Liver cancer, especially hepatocellular carcinoma (HCC), is particularly prevalent in Africa and Asia. HCC affects the Hispanic population of the United States at a rate double that of the white population. The majority of people with HCC will die within 1 year of its detection. This high case-fatality rate can in part be attributed to lack of diagnostic methods that allow early detection. How to establish a methodology to identify the high-risk individuals for HCC remains to be investigated. The multi-factorial and multi-step nature in the molecular pathogenesis of human cancers must be taken into account in both the design and interpretation of studies to identify markers which will be useful for early detection of cancer. Our recent studies demonstrated that a mini-array of multiple tumor-associated antigens (TAAs) might enhance autoantibody detection for diagnosis of HCC, especially for the alpha fetoprotein (AFP)-negative cases. It also suggested that different types of cancer might require different panels of TAAs to achieve the sensitivity and specificity required to make immunodiagnosis a feasible adjunct to tumor diagnosis. PMID:17289549

  4. Pro-inflammatory role of Anti-Ro/SSA autoantibodies through the activation of Furin-TACE-amphiregulin axis.

    Science.gov (United States)

    Lisi, Sabrina; Sisto, Margherita; Lofrumento, Dario Domenico; Cucci, Liana; Frassanito, Maria Antonia; Mitolo, Vincenzo; D'Amore, Massimo

    2010-09-01

    Prolonged inflammation can be detrimental because it may cause host toxicity and tissue damage. Indeed, excessive production of inflammatory cytokines is often associated with many autoimmune diseases. In this study we demonstrate that the anti-Ro/SSA autoantibodies (Abs) stimulate the production of pro-inflammatory cytokines IL-6 and IL-8 by human healthy salivary gland epithelial cells (healthy SGEC). The secretion of these cytokines is due to amphiregulin (AREG) that is overexpressed in healthy SGEC treated with anti-Ro/SSA Abs and in Sjögren's syndrome. We have discovered that the up-regulation of AREG occurs through TNF-alpha produced following anti-Ro/SSA Abs treatment. The gene silencing technique was used to study the AREG-TNF-alpha-IL-6/IL-8 secretion pathway, demonstrating that: (i) TNF-alpha gene silencing provokes a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated healthy SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-alpha-induced IL-6 and IL-8 secretion in healthy SGEC treated with anti-Ro/SSA Abs. These findings indicate that TACE-mediated AREG shedding plays a critical role in TNF-alpha-induced IL-6 and IL-8 secretion by the human healthy salivary gland epithelial cells, suggesting that this may be one of the possible intracellular mechanisms involved in the salivary glands inflammatory response in Sjögren's syndrome.

  5. Anti-asialoglycoprotein receptor autoantibodies, detected by a capture-immunoassay, are associated with autoimmune liver diseases.

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    Yoshioka M

    2002-04-01

    Full Text Available In autoimmune chronic active hepatitis (AIH and primary biliary cirrhosis (PBC, various autoantibodies including anti-asialoglycoprotein receptor (ASGPR antibodies have been found in patients' sera. We have previously developed a mouse monoclonal antibody against rat and human ASGPR. In this study, we developed a capture enzyme-linked immunosorbent assay (ELISA for detection of anti-ASGPR antibodies using this monoclonal antibody and investigated the occurrence of anti-ASGPR antibodies in the sera of patients with various liver diseases. Serum samples were obtained from 123 patients with various liver diseases, including 21 patients with AIH and 40 patients with PBC. In this capture ELISA, the target antigen in the crude rat liver membrane extracts was captured on the ELISA wells by the ASGPR-specific mouse monoclonal antibody. Thus, the cumbersome process of antigen purification was rendered unnecessary. Using this capture ELISA, we detected the anti-ASGPR antibody in 67% of the patients with AIH, in 100% of the patients with PBC, and in 57% of the patients with acute hepatitis type A. However, the anti-ASGPR antibody was rarely detected in patients with other liver diseases such as primary sclerosing cholangitis and obstructive jaundice. Our findings suggest that this capture ELISA would be useful for the detection of anti-ASGPR antibodies in autoimmune liver diseases.

  6. Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset.

    Science.gov (United States)

    Metz, Thomas O; Qian, Wei-Jun; Jacobs, Jon M; Gritsenko, Marina A; Moore, Ronald J; Polpitiya, Ashoka D; Monroe, Matthew E; Camp, David G; Mueller, Patricia W; Smith, Richard D

    2008-02-01

    Novel biomarkers of type 1 diabetes must be identified and validated in initial, exploratory studies before they can be assessed in proficiency evaluations. Currently, untargeted "-omics" approaches are underutilized in profiling studies of clinical samples. This report describes the evaluation of capillary liquid chromatography (LC) coupled with mass spectrometry (MS) in a pilot proteomic analysis of human plasma and serum from a subset of control and type 1 diabetic individuals enrolled in the Diabetes Autoantibody Standardization Program, with the goal of identifying candidate biomarkers of type 1 diabetes. Initial high-resolution capillary LC-MS/MS experiments were performed to augment an existing plasma peptide database, while subsequent LC-FTICR studies identified quantitative differences in the abundance of plasma proteins. Analysis of LC-FTICR proteomic data identified five candidate protein biomarkers of type 1 diabetes. alpha-2-Glycoprotein 1 (zinc), corticosteroid-binding globulin, and lumican were 2-fold up-regulated in type 1 diabetic samples relative to control samples, whereas clusterin and serotransferrin were 2-fold up-regulated in control samples relative to type 1 diabetic samples. Observed perturbations in the levels of all five proteins are consistent with the metabolic aberrations found in type 1 diabetes. While the discovery of these candidate protein biomarkers of type 1 diabetes is encouraging, follow up studies are required for validation in a larger population of individuals and for determination of laboratory-defined sensitivity and specificity values using blinded samples.

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

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    E. Kampmann

    2015-01-01

    Full Text Available 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.

  8. Comparable autoantibody serum levels against amyloid- and inflammation-associated proteins in Parkinson's disease patients and controls.

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    Walter Maetzler

    Full Text Available Naturally occurring autoantibodies (NAbs against a number of potentially disease-associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42, Alpha-synuclein (Asyn, myelin basic protein (MBP, myelin oligodendrocyte glycoprotein (MOG, and S100 calcium binding protein B (S100B have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer's (AD and Parkinson's disease (PD. Whereas the (reduced occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings. We therefore aimed, in a cross-sectional approach, to determine serum titres of the above NAbs in a cohort of 93 PD patients (31 of them demented and 194 controls. Levels were correlated with demographic and clinical variables, cerebrospinal fluid Abeta1-42, total tau and phospho-tau levels, as well as with single nucleotide polymorphisms (SNPs of genes which either have been reported to influence the immune system, the amyloid cascade or the occurrence of PD (ApoE, GSK3B, HLA-DRA, HSPA5, SNCA, and STK39. The investigated NAb titres were neither significantly associated with the occurrence of PD, nor with demographic and clinical parameters, neurodegenerative markers or genetic variables. These results argue against a major potential of blood-borne parameters of the adaptive immune system to serve as trait or state markers in PD.

  9. 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.

  10. Antiphospholipase A2 Receptor Autoantibodies: A Comparison of Three Different Immunoassays for the Diagnosis of Idiopathic Membranous Nephropathy

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    Astrid Behnert

    2014-01-01

    Full Text Available Background. The recent identification of circulating autoantibodies directed towards the M-type phospholipase A2 receptor (PLA2R has been a major advancement in the serological diagnosis of idiopathic membranous nephropathy (IMN, a common cause of nephrotic syndrome in adults. The goal of this study was to compare the performance characteristics of two commercial assays as well as the first addressable laser bead immunoassay (ALBIA developed for the detection of anti-PLA2R antibodies. Methods. Serum samples of 157 IMN patients and 142 controls were studied. Samples were tested by a cell based immunofluorescence assay (CBA-IFA, Euroimmun, Germany, by ELISA (Euroimmun, and by a novel ALBIA employing an in vivo expressed recombinant human PLA2R. Results. Overall, the three assays showed significant qualitative and quantitative correlation. As revealed by receiver operating characteristic analysis, the ALBIA correlated better with the CBA-IFA than the ELISA (P=0.0003. The clinical sensitivities/specificities for IMN were 60.0% (51.0–68.5%/98.6% (95.0–99.8% and 56.2% (47.2–64.8%/100.0% (97.4–100.0% for ALBIA and CBA-IFA, respectively. Conclusion. The ALBIA represents a promising assay for the detection of anti-PLA2R antibodies showing similar performance to the CBA-IFA and the advantage of ease of use and suitability for high throughput, rapid turnaround times, and multiplexing.