Fc gamma receptor polymorphisms in systemic lupus erythematosus - Association with disease and in vivo clearance of immune complexes

Objective, Fc receptors for IgG (Fc gammaR) play a prominent role in the cl earance of immune complexes in systemic lupus erythematosus (SLE). Polymorp hisms of Fc gammaR have been proposed as genetic factors that influence sus ceptibility to SLE, We analyzed 3 functional Fc gammaR polymorphisms in a s trictly 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 Fc gammaR-genomic regions in allotype-specif ic polymerase chain reactions was used to distinguish the genotypes, In add ition, we analyzed the Fc gammaR genotypes of 13 patients with SLE who part icipated in a study determining the half-life of IgG-coated erythrocytes in the blood. Results. We found a strong trend toward skewing of Fc gamma RIIa, with an e nrichment of the homozygous Fc gamma RIIa-R/R131 genotype in patients compa red with controls. We did not find a correlation between this genotype and the development of lupus nephritis, However, we established that the half-l ife of IgG-coated erythrocytes in the blood was prolonged in patients expre ssing the Fc gamma RIIa-R/R131 genotype, The homozygous Fc gamma RIIIa-F/F1 58 genotype was found more frequently in patients with arthritis and/or ser ositis, Conclusion, In Caucasian populations, the R/H polymorphism of Fc gamma RIIa is a minor determinant in susceptibility to SLE, whereas the V/F polymorph ism of Fc gamma RIIIa is associated with a set of disease manifestations, N otably, the R/H polymorphism of Fc gamma RIIa affects the clearance of immu ne complexes in vivo, which may influence the course of a disease such as S LE.