Analysis of autoantibody repertoires in small- and medium-sized vessels vasculitides. Evidence for specific perturbations in polyarteritis nodosa, microscopic polyangiitis, Churg–Strauss syndrome and Wegener's granulomatosis (original) (raw)
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Individual and stable autoantibody repertoires in healthy individuals
Autoimmunity
In the era towards precision medicine, we here present the individual specific autoantibody signatures of 193 healthy individuals. The self-reactive IgG signatures are stable over time in a way that each individual profile is recognized in longitudinal sampling. The IgG autoantibody reactivity towards an antigen array comprising 335 protein fragments, representing 204 human proteins with potential relevance to autoimmune disorders, was measured in longitudinal plasma samples from 193 healthy individuals. This analysis resulted in unique autoantibody barcodes for each individual that were maintained over one year's time. The reactivity profiles, or signatures, are person specific in regards to the number of reactivities and antigen specificity. Two independent data sets were consistent in that each healthy individual displayed reactivity towards 0-16 antigens, with a median of six. Subsequently, four selected individuals were profiled on in-house produced high-density protein arrays containing 23,000 protein fragments representing 14,000 unique protein coding genes. Based on a unique, broad and deep longitudinal profiling of autoantibody reactivities, our results demonstrate a unique autoreactive profile in each analyzed healthy individual. The need and interest for broad-ranged and high-resolution molecular profiling of healthy individuals is rising. We have here generated and assessed an initial perspective on the global distribution of the self-reactive IgG repertoire in healthy individuals, by investigating 193 well-characterized healthy individuals. HIGHLIGHTS A unique longitudinal profiling of autoantibody repertoires in healthy individuals Autoantibody profiles are highly individual and stable over time All individuals display IgG binding to human protein fragments The specificity of disease associated autoantigens needs to be thoroughly characterized The identification of a small set of highly reactive autoantigens Importance of stringent antigen and sample specific cutoffs for defining reactivity ARTICLE HISTORY
Autoantibody diagnostics in clinical practice
Autoimmunity Reviews, 2012
Disease associated autoantibodies (AAB) are important biomarkers not only to confirm the diagnosis of the respective systemic autoimmune disease but also to diagnose the disease at very early stages (mono-or oligosymptomatic manifestations) or to diagnose the respective disease without the typical clinical manifestations (atypical forms). A confirmation of the diagnosis in early stages is required, if patients should benefit from early therapeutic intervention. Furthermore, AAB determinations are used for prognostic purposes and for monitoring of disease activity or response to therapy. For the advancement of autoantibody diagnostics in clinical practice the following aspects have to be considered: (i) The search for novel clinically relevant AAB and the identification of autoantigenic targets of AAB broadened the spectrum of autoimmune diagnostics and permit the diagnosis of former idiopathic diseases. (ii) To obtain steady diagnostic variables of clinically relevant AAB, the evaluation studies have to be standardized. (iii) Several special features and novel developments of autoantibody diagnostics make correct interpretation of antibody test results increasingly difficult. (iv) Beside standardization of AAB detection methods and quality management efforts the improvement of autoantibody diagnostics depends on further development of diagnostic algorithms including cost-effective multiparametric analyses.
The Frequency of Non-Organ-Specific Autoantibodies in Patients with
Archives of Clinical Infectious Diseases, 2006
Background: Increased levels of non-organ-specific autoantibodies are frequently seen in patients suffering from chronic hepatitis C (CHC); however, the etiology and its effects on the course of the disease and response to therapy are largely undetermined. Particularly, it seems of utmost importance to define whether this increase is solely an insignificant coincidence or a major finding which have an impact on the course of the disease. Materials and methods: Fifty-two patients with CHC (case group) and 52 aged-and sex-matched IBS patients (controls) were enrolled. The sera of all subjects were checked for non-organ-specific autoantibodies, including antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-mitochondrial antibody (AMA), and antiliver/kidney microsomal antibody (ALKM). All cases underwent a liver biopsy and treated with a 12-month course of combination therapy with interferon and ribavirin. Results: The mean age of cases and controls was 32.8±12.7 and 31.6±14.1 years, respectively. The overall frequency of non-organ-specific antibodies was significantly higher in anti-HCV positive patients in comparison with controls (36.5% vs 7.7%, p<0.001). Seropositivity of ANA and ASMA was significantly higher in patients with CHC than in controls (11.5% vs. 1.9%, p<0.05 and 13.5% vs. 1.9%, p<0.027, respectively). There was no significant relationship between seropositivity of different autoantibodies and patients' age and sex, duration of disease and serum aminotransferases levels. Nor this seropositivity had significant relationship with grade and stage of the liver disease and response to treatment, while serum globulin level was significantly higher in ANA positive patients. Conclusion: Seroprevalence of ANA and ASMA seems to be higher in patients with CHC but its impact on the severity of disease and response to therapy is the subject for further investigations.
Frontiers in immunology, 2018
Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epi...
Autoantibodies in systemic vasculitis
Australian and New Zealand Journal of Medicine, 1991
We have studied 495 sera that were referred to us from patients suspected on clinical andlor histological grounds to have a small vessel vasculitis. These sera were tested for antibodies against neutrophil cytoplasm antigens (anti-neutrophil cytoplasm antibodies, ANCA) using assays based on neutrophil acid extract, myeloperoxidase and elastase. Such antibodies are commonly found in Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA), and sometimes in other small vessel vasculitides. One hundred and twenty-six of these sera (25%) were positive in the acid extract ELISA, 68 (14%) in the assay for anti-myeloperoxidase antibodies and 35 (16%) in the assay for antielastase antibodies. A total of 166 sera (34%) were positive for antibodies against neutrophil cytoplasm constituents. No ANCA, anti-myeloperoxidase or anti-elastase antibodies were detected in 26 convalescent sera from patients either with W G or MPA, or who had previously been positive. The mean time between positive and negative sera was eight weeks (range three weeks to six months) and three out of three who relapsed again developed ANCA of the same specificity as the original sera. Of the 228 sera also tested for anti-GBM antibodies, 13 (5.7%) were positive. All these contained antibodies against neutrophil cytoplasm constituents (three against the acid extract, eight against myeloperoxidase and two against elastase). Forty-nine of the 74 sera (66%) tested for ANA were positive. Twenty-nine (39%) had a speckled and 20 (27%) had a homogeneous pattern. Twenty of these were positive for ANCA or antimyeloperoxidase or anti-elastase antibodies and 29 were negative. ANCA, anti-myeloperoxidase and anti-elastase antibodies are common in patients in whom a vasculitis is suspected on clinical and/or histological grounds. The presence of these antibodies correlates with disease activity. Anti-GBM antibodies and ANA are not uncommon in this group. A single ELISA for ANCA is insufficient to detect all antibodies directed against neutrophil cytoplasm constituents.
Autoantibody Profiling in a Cohort of Pediatric and Adult Patients With Autoimmune Hepatitis
Journal of Clinical Laboratory Analysis, 2014
Background: Autoimmune hepatitis (AIH) is a rare condition characterized by the presence of autoantibodies distinctive of type 1 AIH (AIH-1) and type 2 AIH (AIH-2). The aim of this study was to evaluate the autoantibody profile in a cohort of pediatric and adult AIH patients, using both indirect immunofluorescence (IIF) and a new multiplexed line-blot assay. Methods: Sera from 63 pediatric and 53 adult AIH patients were tested for antinuclear (ANA), antismooth muscle (SMA), anti-liver kidney microsome 1 (anti-LKM1), anti-liver cytosol 1 (anti-LC1) autoantibodies using IIF methods; for anti-LKM1, anti-LC1, and soluble liver antigen/liver-pancreas (anti-SLA/LP) autoantibodies using the line-blot; for anti-F-actin autoantibodies using IIF both on VSM47 cell-line and on rat intestinal epithelial cells. Results: AIH-1 was the most common type of AIH in the adult cohort (73.6%), while AIH-2 was the most com-mon AIH in the pediatric cohort (61.9%). Both in adult and pediatric AIH-2 anti-LKM1 were the prevalent autoantibodies. In pediatric AIH-2 anti-LC1 autoantibodies were more frequent than in adult AIH-2 (59 vs. 28.6%), and in 35.9% of cases they were present alone. In 17 patients anti-LC1 autoantibodies were detected only with the line-blot assay. The levels of anti-LKM1 and of anti-LC1 were not different between adult and pediatric AIH, and the overall agreement between the results obtained with the two IIF methods for F-actin detection was 98.8% (CI 95%: 94.4-99.7%). Conclusions: The line-blot assay showed a higher sensitivity than IIF for anti-LC1 detection. Anti-LKM1 and anti-LC1 autoantibody levels are not different in adults and children. An almost perfect agreement between the two IIF methods for anti-F-actin detection has been observed.
Autoantibody profile in systemic sclerosis
Acta medica Iranica
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 assa...