Interferon signature in the development of SLE: molecular mechanisms, approaches to diagnosis and treatment
TO NakonechnayaIrina A. ShaginaM.Y. MyshkinZYu MutovinaE.V. RyazantsevaDmitriy M. ChudakovMaria A. TurchaninovaOV Britanova
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Abstract:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation of connective tissue and damage to various organs, including joints, skin, kidneys and heart. The disease has a significant gender predisposition and is more common in women. The pathogenesis of SLE is based on a violation of immunological tolerance, accompanied by activation of B lymphocytes and the production of autoantibodies. Recent advances in basic research have significantly deepened the understanding of the immunopathogenetic mechanisms of SLE, which justifies the use of new pharmacotherapeutic approaches. These approaches involve the use of biological drugs aimed at blocking the activity of type I interferon (IFN) or its receptors. The article discusses the molecular mechanisms of activation of the interferon response in SLE, modern methods for diagnosing the interferon signature, and new approaches to treatment aimed at blocking the interferon pathway. The possible role of the interferon signature in the stratification of SLE patients is also discussed. Such stratification will make it possible to more effective select treatment regimens taking into account the individual characteristics of the immune response of each patient. This may increase the effectiveness of treatment, reduce the likelihood of side effects and improve the prognosis for patients with SLE.Keywords:
Pathogenesis
Objective:To study the characteristics of autoantibodies in patients with primary hepatocellular carcinoma(HCC).Methods:83 patients with primary hepatocellular carcinoma(HCC)were studied.Different autoantibodies were detected by indirect immunofluorescent assay(IIF,Euroimmuno,Germany).Results:31 of 83 cases were found autoantibodies(37.3%),in whom 64 patients were in HBV infection,with 23 autoantibodies positive(35.9%).8 were autoantibody-positive in 16 patients with HCV infection(50.0%).There was no significant differences between the two groups(P0.05).24.1%(20/83)or 12.1%(10/83)or 1.2%(1/83)patients were positive for one,two or three kinds of autoantibodies respectively.Anti-nuclear antibody(ANA)was the most popular(24.1%)than others.Anti-cytoskeleton(CS)was 13.3%,whereas anti-smooth muscle antibody(SMA)was 9.6% and anti-mitochondria antibody(AMA)4.8% respectively.It was shown that anti-Ro-52 or anti-CENP-B was positive by ANA analysis.Comparing AFP normal with abnormal patients,antoantibody rate(22.2% vs 36.8%)had no significant difference.There were no remarkable difference between autoantibodies positive group and autoantibodies negative group for HBV-DNA.Conclusion:Non-organ-specific autoantibodies—ANA,CS,SMA and AMA can be detected in 37.3% patients with HCC.The highest detection rate is ANA,the next is CS and SMA,and the lowest is AMA.All of detected autoantibodies are shown with low titer(1∶100).Concentration of AFP and autoantibodies is not shown significant correlation.There is no remarkable difference in autoantibodies between HBV-DNA positive group and negative group.
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The goal of this study was to address whether antiislet autoantibodies appear sequentially or simultaneously before the onset of type I diabetes. We analyzed sequential serum samples from 155 siblings and offspring (aged < 7 yr) of patients with type I diabetes from the Denver Diabetes Autoimmunity Study in the Young study and from a separate group of first degree relatives (aged 2-40 yr) for autoantibodies reacting with three defined autoantigens: glutamic acid decarboxylase (GAD65), insulin, and ICA512/IA-2. The youngest age at which 1 of the 3 autoantibodies appeared was 1.1 yr, and the oldest was 60.9 yr. Of the total 26 autoantibody conversion events observed, in only 3 instances did more than 1 autoantibody appear simultaneously. Among individuals (n = 12) with sequential conversion to expression of multiple autoantibodies, anti-GAD65 autoantibodies or antiinsulin autoantibodies appeared first (4 expressed antiinsulin autoantibodies first, and 8 anti-GAD65 autoantibodies first). We conclude that antiislet autoantibodies usually appear sequentially and not simultaneously. This corroborates early suggestions that humoral autoimmunity to islets develops chronically in a process usually measured in months to years. As expression of multiple autoantibodies is associated with a high risk of progression to diabetes, and sequential appearance of autoantibodies can occur late in life, long term follow-up is necessary to fully delineate the relationship of diabetes risk to autoantibody expression.
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A paradigmatic feature of autoimmune rheumatic diseases (ARD) is the presence of multiple autoantibodies. The use of antibody profiles in the study of ARD therefore should be the best strategy for both diagnostic and classification purposes. To this end, systems using micronized components (protein chips or arrays), consisting of solid phase-linked autoantigens capable of simultaneously detecting many autoantibodies at the same time, are particularly suitable for testing autoantibody profiles. In the near future, extended disease-specific autoantibody profiles consisting of dozens, if not hundreds, of autoantibodies will be able to define each patient's autoantibody fingerprint and identify subclasses of patients with different prognostic characteristics and different therapeutic responses.
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The pathophysiology of glandular dysfunction in Sjögren's syndrome (SS) has not been fully elucidated. Previously, we reported the presence of autoantibodies to AQP-5 in patients with SS, which was associated with a low resting salivary flow. The purpose of this study was to investigate the presence of anti-AQP1 autoantibodies. To detect anti-AQP1 autoantibodies, cell-based indirect immunofluorescence assay was developed using MDCK cells that overexpressed human AQP1. By screening 112 SS and 52 control sera, anti-AQP1 autoantibodies were detected in 27.7% of the SS but in none of the control sera. Interestingly, the sera that were positive for anti-AQP1 autoantibodies also contained anti-AQP5 autoantibodies in the previous study. Different from anti-AQP5 autoantibodies, the presence of anti-AQP1 autoantibodies was not associated with the salivary flow rate. Although anti-AQP1 autoantibodies are not useful as a diagnostic marker, the presence of autoantibodies to AQP1 may be an obstacle to AQP1 gene therapy for SS.
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Autoimmune disease is the result of interplay between genetic and environmental factors, Immunoregulatory genes and thyroid specific genes play important roles in the pathogenesis of autoimmune thyroid diseases.
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Autoimmune thyroid diseases; Polymorphism, single nucleotide; Pathogenesis
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Objective:To understand autoantibody status by the serological analysis for difficult blood cross matching caused by autoantibody,and explore the test strategy for positive autoantibody patients.Method:Using saline method(room temperature,37℃,4℃),Polybrene method,Traditional antihumanglobulin test,microcolumn gel immuno-assay identified the antibody specificity for autoantibody patients.According to the characteristics of autoantibodies in patients,different experimental methods were used for blood cross matching in order to choose the right blood for clinical,and the effect of transfusion was observed.Result:In 119positive autoantibodies patients,88samples were warm autoantibodies(73.95%).Among them,12patients were with specific antibodies:Anti-cE 7,anti-E 2,anti-Jkb 1,anti-Lea1,anti-Leb 1.And 9patients were with specific anti autoantibodies:anti-Ce3,anti-E 2,anti-c 1,anti-cE 1,anti-M 1cases.Twenty samples were cold autoantibodies(16.81%),including 1cases with anti-E antibody.Four samples were warm and cold mixed autoantibodies(3.36%);7samples were hyperglobulinemia(5.88%).According to the characteristics of autoantibodies,using different treatment measures achieved satisfactory effect of transfusion.Conclusion:In patients with positive autoantibodies,different autoantibodies characteristic for blood test would be different.In order to ensure the clinical blood transfusion safety,reasonable and effective,we should master the indications for transfusion,to avoid unnecessary blood transfusion.For blood cross match test,we should select suitable experimental methods according to the antibody characteristic,to eliminate the autoantibodies effect in patients.
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Hypertension has complicated pathogenesis.Because of the complexity,in this article the hypertension pathogenesis was divided into several different levels to discuss,which were basic pathogenesis,syndrome pathogenesis,symptom manifestation pathogenesis,disease pathogenesis and micro pathogenesis.The relationship between the above levels and the theoretic and clinical values of each level were analyzed.The significance of syndrome pathogenesis in the study on hypertension pathogenesis was emphasized.
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