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      IgA Anti-β2-Glycoprotein I Autoantibodies Are Associated with an Increased Risk of Thromboembolic Events in Patients with Systemic Lupus Erythematosus

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          Abstract

          Background

          The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial.

          Methodology/Principal Findings

          To address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-β2-glycoprotein I (isolated IgA anti-β2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-β2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-β2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-β2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-β2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin).

          Conclusions/Significance

          The presence of isolated IgA anti-β2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-β2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity.

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          Most cited references17

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          Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.

          M Hochberg (1997)
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            The antiphospholipid syndrome.

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              Premature coronary-artery atherosclerosis in systemic lupus erythematosus.

              Premature coronary artery disease is a major cause of illness and death in patients with systemic lupus erythematosus, but little is known about the prevalence, extent, and causes of coronary-artery atherosclerosis. We used electron-beam computed tomography to screen for the presence of coronary-artery calcification in 65 patients with systemic lupus erythematosus (mean [+/-SD] age, 40.3+/-11.6 years) and 69 control subjects (mean age, 42.7+/-12.6 years) with no history of coronary artery disease. When calcification was detected, the extent was measured by means of the Agatston score. The frequency of risk factors for coronary artery disease was compared in patients and controls, and the relation between the patients' clinical characteristics and the presence or absence of coronary-artery calcification was examined. The two groups were similar with respect to age, race, and sex. Coronary-artery calcification was more frequent in patients with lupus (20 of 65 patients) than in control subjects (6 of 69 subjects) (P=0.002). The mean calcification score was 68.9+/-244.2 in the patients and 8.8+/-41.8 (P<0.001) in controls. Levels of total, high-density lipoprotein, and low-density lipoprotein cholesterol were not elevated in patients with lupus, but levels of triglycerides (P=0.02) and homocysteine (P<0.001) were. Among patients with lupus, measures of disease activity were similar in those with and those without coronary-artery calcification, but those with calcification were more likely to be older (P<0.001) and male (P=0.008). In patients with systemic lupus erythematosus, the prevalence of coronary-artery atherosclerosis is elevated and the age at onset is reduced. Early detection of atherosclerosis may provide an opportunity for therapeutic intervention. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                19 August 2010
                : 5
                : 8
                : e12280
                Affiliations
                [1 ]Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America
                [2 ]Section of Rheumatology, Department of Medicine, University of Southern California, Los Angeles, California, United States of America
                [3 ]Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America
                [4 ]Division of Pulmonary and Critical Care, University of Cincinnati Medical Center, Cincinnati, Ohio, United States of America
                [5 ]Section of Rheumatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America
                [6 ]Department of Pathology, University of Chicago, Chicago, Illinois, United States of America
                [7 ]Sections of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America
                [8 ]Section of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America
                [9 ]Section of Nephrology, Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, United States of America
                New York University, United States of America
                Author notes

                Conceived and designed the experiments: NJS JSL. Performed the experiments: NJS RB RK DM FM TA SV MB MS AC JB JSL. Analyzed the data: NJS RB RK DM FM TA SV MB MS AC JB JSL. Contributed reagents/materials/analysis tools: NJS RB RK DM FM TA SV MB MS AC JB JSL. Wrote the paper: NJS JSL.

                Article
                10-PONE-RA-16712R1
                10.1371/journal.pone.0012280
                2924386
                20808864
                bdd8f39e-4ab3-4e47-8726-31e64e2df03c
                Sweiss et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 25 February 2010
                : 26 July 2010
                Page count
                Pages: 6
                Categories
                Research Article
                Rheumatology/Autoimmunity, Autoimmune, and Inflammatory Diseases
                Rheumatology/Imaging and Biomarkers
                Rheumatology/Systemic Lupus Erythematosos

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                Uncategorized

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