Anticardiolipin IgG subclasses association of IgG2 with arterial and/or venous thrombosis

Abstract

Objective. To determine whether the presence of anticardiolipin antibodies (aCL) of a specific IgG subclass is associated with clinical complications of the antiphospholipid antibody syndrome (APS) and whether polymorphisms of Fc receptors for IgG (FcyR) with differential binding preferences contribute to an increased risk of thrombotic complications.Methods. In 60 patients with IgG aCL, we assessed clinical complications of the APS, measured the level of antibody activity, and determined the IgG subclass distribution of aCL by a modified enzymelinked immunosorbent assay (ELISA) with murine antihuman IgG subclass monoclonal antibodies. Selective IgG subclass adsorption studies were performed to determine the relative contribution of specific IgG subclasses to overall aCL activity. Fcy receptor IIA (FcyRIIA) genotypes of aCL patients with thrombosis and of non-systemic lupus erythematosus controls were determined by polymerase chain reaction amplification of genomic DNA and allele-specific probes.Results. IgG2 aCL, detected in 75% of the patients, was the major subclass of aCL. Selective adsorption studies demonstrated that IgG2, in contrast to IgGl, was the predominant subclass responsible for aCL reactivity. IgG2 aCL was the only subclass associated with clinical complications, specifically, arterial

FcγR expression on NK cells influences disease severity in rheumatoid arthritis

“…The polymorphism at amino acid 131, which changes the IgG binding specificity of FcgRIIA, has been implicated in both infectious and autoimmune diseases. 12,13,20,21 Shown in Table 2 are the results of the FcgRIIA-131 genotyping from RA patients and normal controls. No differences in the frequency of FcgRIIA-131R or FcgRIIA-131H genotypes were observed between the normal donors and the RA subjects, which is consistent with previous reports.…”

“…8 We have recently found that FcgRIIc is predominantly expressed on NK cells and that it is able to trigger NK cell lysis of antibody-coated target cells and cytokine production. [9][10][11] Allelic polymorphisms of FcgR genes have been described 9,[12][13][14][15] that affect the function of cells of the innate immune system including FcgRIIIA, 14,16 FcgRIIA, 17 FcgRIIC, 7,18 and FcgRIA. 19 In general, these polymorphisms have been shown to alter the ligand binding specificity of particular FcgR, such as FcgRIIa, 17 and FcgRIIIa.…”

“…19 In general, these polymorphisms have been shown to alter the ligand binding specificity of particular FcgR, such as FcgRIIa, 17 and FcgRIIIa. 14,16 These allelic polymorphisms have proved to be clinically significant in infectious 20,21 and autoimmune 12,13,[22][23][24] diseases.…”

Role of the Fcγ receptor IIA polymorphism in the antiphospholipid syndrome: An international meta‐analysis

“…SLE ϭ systemic lupus erythematosus. Three of the research teams used criteria (11,30,31) other than the preliminary criteria for the classification of APS. Apart from the essential clinical features of vascular thrombosis and complications of pregnancy (16), the alternative criteria allowed patients with thrombocytopenia (in 3 studies) or transient ischemic attacks (in 1 study) to be classified as having APS if they also had aCL or lupus anticoagulant.…”

“…Binding to the H131 variant can initiate more pronounced monocyte, platelet, and endothelial cell activation in the context of an IgG2 immune response, inducing a prothrombotic phenotype. Since autoimmune disease-associated aCL show IgG2 predominance (10,11), one might expect an enrichment of the H131 allele in APS patients (11). However, the data are not yet conclusive (12,13).…”