Overrepresentation of the Fc gamma receptor type IIA R131/R131 genotype inCaucasoid systemic lupus erythematosus patients with autoantibodies to C1qand glomerulonephritis

Objective. To test the hypothesis that there is an association between the Fc gamma receptor type IIA (Fc gamma RIIA)-H/R131 polymorphism and autoanti bodies to the collagenous region (CLR) of C1q in patients with systemic lup us erythematosus (SLE). Methods. One hundred ninety-five Caucasoid lupus patients were studied. Ant i-C1q(CLR) antibodies in serum were measured by enzyme-linked immunosorbent assay (ELISA) and Fc gamma RIIA genotype analysis was performed by polymer ase chain reaction. Immunoglobulin subclass of the autoantibodies was measu red by ELISA. Results. Fifty-six patients were anti-C1q antibody positive, and Ig subclas s analysis indicated a predominance of IgG2 anti-C1q antibodies. Analysis o f the SLE population as a whole revealed nea significant difference in the allele frequencies of R131 and H131 compared with controls. There was, howe ver, a significantly increased frequency of the R131 allele both in the ant i-C1q-positive subgroup of patients (chi(2) = 7.66, P < 0.01) and in the 71 patients with nephritis (chi(2) = 7.76, P < 0.01), compared with controls. Conclusion. Fc gamma RIIA-R131 constitutes a heritable susceptibility facto r for the development of SLE with manifestations in the kidney in Caucasoid patients. The close associations demonstrated between this Fc gamma RII va riant, antibodies to C1q(CLR), and glomerulonephritis may be due to a failu re of clearance of the potentially pathogenic IgG2 autoantibody.