Clinical Characterization of Antiphospholipid Syndrome by Detection of IgG Antibodies Against β2‐Glycoprotein I Domain 1 and Domain 4/5: Ratio of Anti–Domain 1 to Anti–Domain 4/5 As a Useful New Biomarker for Antiphospholipid Syndrome
Laura AndréoliCecilia Beatrice ChighizolaCecilia NalliMaria GerosaMaría Orietta BorghiFrancesca PregnolatoC. GrossiAlessandra ZanolaFlavio AllegriGary L. NormanMichael MählerPier Luigi MeroniAnǵela Tincani
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Objective It has been suggested that only antibodies against domain 1 (D1) of β 2 ‐glycoprotein I (β 2 GPI) are pathogenic and diagnostic. The role of antibodies against other β 2 GPI domains is still debated. This study was undertaken to evaluate the clinical relevance of domain specificity profiling of anti‐β 2 GPI IgG antibodies in antiphospholipid syndrome (APS) patients and in control groups of patients with systemic autoimmune rheumatic diseases and in asymptomatic antiphospholipid antibody (aPL) carriers. Methods We evaluated 159 subjects with persistently positive, medium or high‐titer anti‐β 2 GPI IgG, including 56 patients with thrombotic (obstetric or nonobstetric) primary APS, 31 women with obstetric primary APS, 42 aPL‐positive patients with systemic autoimmune rheumatic diseases, and 30 asymptomatic aPL carriers. One hundred healthy donors were included. Anti‐β 2 GPI D1 and D4/5 IgG were tested on research enzyme‐linked immunosorbent assays containing recombinant β 2 GPI domains. Results As compared to other groups, aPL carriers displayed higher frequency/titer of anti‐D4/5 IgG. Unlike anti‐D4/5, anti‐D1 IgG antibodies were more frequent and at higher titer in triple than in single or double aPL‐positive subjects. An anti‐D1 to anti‐D4/5 ratio of ≥1.5 was predictive of systemic autoimmunity (odds ratio 3.25 [95% confidence interval 1.45–7.49], P = 0.005). Neither anti‐D1 nor anti‐D4/5 antibodies were associated with APS clinical criteria. Conclusion Anti‐D1 IgG is the preferential specificity not only in vascular and obstetric primary APS, but also in patients with systemic autoimmune rheumatic disease with no clinical features of APS. Conversely, aPL carriers do not have a polarized profile toward D1. Combined testing for anti‐β 2 GPI IgG with different domain specificity allows a more accurate aPL profiling, with polarization toward anti‐D1 IgG as a possible fingerprint of systemic autoimmunity.Keywords:
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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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We compared the effect of plasmapheresis on antineuronal autoantibody titers in the serum and CSF of 3 patients with CNS paraneoplastic syndromes. Plasmapheresis reduced the serum autoantibody titer to 20% of the initial levels in the 3 patients, but the CSF autoantibody titer decreased only in the patient with severe damage of the blood-brain barrier.
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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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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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The PcrV cap structure of the type III secretory apparatus of Pseudomonas aeruginosa is a vaccine target. Human immunoglobulin G (IgG) molecules extracted from sera containing high or low anti-PcrV titers were tested for their effects against P. aeruginosa pneumonia in a mouse model. Among 198 volunteers, we selected the top 10 high anti-PcrV titer sera and the bottom 10 low anti-PcrV titer sera and extracted the IgG fraction from each serum sample. First, we examined the effects of the IgG against virulent P. aeruginosa. A lethal dose of P. aeruginosa premixed with saline, low titer human IgG, high titer human IgG, or rabbit-derived polyclonal anti-PcrV IgG was intratracheally administered into the lungs of mice, and their survival and lung inflammation were evaluated for 24 h. The high anti-PcrV titer human IgG had a prophylactic effect. Next, the prophylactic effects of intravenous administration of extracted and pooled high or low anti-PcrV titer human IgG were examined. Here, prophylactic intravenous administration of pooled high anti-PcrV titer human IgG, which showed binding capacity to P. aeruginosa PcrV, was more effective than the administration of its low titer pooled equivalent, and the measured physiological and inflammatory parameters correlated with the anti-PcrV titer levels. This result indirectly implies that high anti-PcrV titers in blood can help to protect against virulent P. aeruginosa infections. In addition, the IgG fractions from such high titer sera have potential to be a source of specific intravenous immunoglobulin products for passive vaccination against virulent P. aeruginosa infections.
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Results of the detection of autoantibodies in patients with chronic HCV-infection are presented. The comparison of importance of autoantibodies both organ specific (to liver specific protein) and organ non-specific (antinuclear and antimitochondrial) is done. The clinical significance of organ specific autoantibodies (to liver specific protein) is high.
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