Fcγ receptor polymorphisms in systemic lupus erythematosus: Association with disease and in vivo clearance of immune complexes

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Abstract
Objective Fc receptors for IgG (FcγR) play a prominent role in the clearance of immune complexes in systemic lupus erythematosus (SLE). Polymorphisms of FcγR have been proposed as genetic factors that influence susceptibility to SLE. We analyzed 3 functional FcγR polymorphisms in a strictly Caucasian population of SLE patients, and determined the influence of these polymorphisms on the clearance of immune complexes in vivo. Methods Genomic DNA was isolated from 230 Caucasian patients with SLE and 154 controls. Amplification of FcγR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. In addition, we analyzed the FcγR genotypes of 13 patients with SLE who participated in a study determining the half-life of IgG-coated erythrocytes in the blood. Results We found a strong trend toward skewing of FcγRIIa, with an enrichment of the homozygous FcγRIIa-R/R131 genotype in patients compared with controls. We did not find a correlation between this genotype and the development of lupus nephritis. However, we established that the half-life of IgG-coated erythrocytes in the blood was prolonged in patients expressing the FcγRIIa-R/R131 genotype. The homozygous FcγRIIIa-F/F158 genotype was found more frequently in patients with arthritis and/or serositis. Conclusion In Caucasian populations, the R/H polymorphism of FcγRIIa is a minor determinant in susceptibility to SLE, whereas the V/F polymorphism of FcγRIIIa is associated with a set of disease manifestations. Notably, the R/H polymorphism of FcγRIIa affects the clearance of immune complexes in vivo, which may influence the course of a disease such as SLE.