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

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Objective To examine the relationship between allelic polymorphisms of IgG receptors (FcγR) and the development of lupus nephritis in a prospective study, and to determine the distribution of FcγR haplotypes (FcγRIIA and FcγRIIIA genotypes) in lupus patients and disease‐free control subjects. Methods We studied 67 Hispanic systemic lupus erythematosus (SLE) patients from a prospective study of outcome and 53 disease‐free control subjects. Patients were followed up longitudinally for 3 years. FcγRIIA and FcγRIIIA genotypes were determined using allele‐specific polymerase chain reaction. Results Nephritis was present in 28% of patients at entry into the study and in 69% at the end of 3 years. In the nephritis group (n = 46), as well as the entire SLE cohort, there was a predominance of genotypes with low‐binding alleles (FcγRIIa‐R131 and FcγRIIIa‐F176) at both loci (SLE nephritis patients 89% versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05–0.6] for risk of nephritis in individuals homozygous for either FcγRIIa‐H131 or FcγRIIIa‐V176). The frequency of individuals homozygous for high‐binding alleles at either locus decreased as the burden of disease increased (P < 0.002, by Mann‐Whitney test). There was no linkage disequilibrium between FcγRIIA and FcγRIIIA in Hispanics, yet in the SLE patients, there was a clear overrepresentation of the FcγRIIa‐R131;FcγRIIIa‐F176 haplotype (SLE patients 48% versus controls 30%) and a decrease in the frequency of the high‐binding haplotype (4% versus 23%) (P < 0.002). Conclusion We observed an increase in the frequency of low‐binding FcγR alleles in an SLE population with a high prevalence of renal disease. The apparent selection for the FcγRIIa‐R131;FcγRIIIa‐F176 haplotype in Hispanic patients suggests that low‐binding alleles of both FcγRIIa and FcγRIIIa confer risk for SLE and may act additively in the pathogenesis of disease, whereas the high‐binding haplotype FcγRIIa‐H131;FcγRIIIa‐V176 is protective, particularly in the homozygous state.