FcγRIIa polymorphism:: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients

Background. FcgammaRIIa is a low affinity receptor that has two co-dominantly expressed alleles, 8131 and H131, which differ in their ability to bind immunoglobulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 and IgG3 than those expressing the 8131 variant. The FcgammaRIIa polymorphism has been shown to be associated with lupus nephritis. Here we evaluated the relevance of FcgammaRIIa gene polymorphism in the development of lupus immune complex (IC)-mediated nephritis by comparing the genotype and allelic distribution of this receptor in lupus nephritis to ethnically matched healthy controls in Brazilians. Methods. 119 systemic lupus erythematosus (SLE) patients and 48 healthy volunteers were recruited. FcgammaRIIa genotyping was performed by PCR with allele-specific primers to distinguish between the two allelic forms (H 131 and R131). Results. Comparison of FcgammaRIIa genotypes distribution in SLE patients with nephritis and in controls showed a significant increase in FcgammaRIIa-R131 homozygosity (P less than or equal to 0.02). The genotype distribution in lupus nephritis (45% with FcgammaRIIa-R/R131, 30% with H/R131 and 25% with H/H131) was distinct from that observed in controls (21% with FcgammaRIIa-R/R131, 52% with H/R131 and 27% with H/H131). In contrast, there was no difference in the distribution of FcgammaRIIa genotypes in lupus without nephritis and controls (P = 0.3). Reinforcing the relevance of FcgammaRIIa polymorphism in IC-mediated nephritis, patients with renal failure had an over-representation of the 8131 allele (70%) when compared with normal controls (47%) (P = 0.06). Conclusions. The skewed distribution of FcgammaRIIa genotypes with the predominance of homozygous R/R131 genotype observed in lupus nephritis emphasizes its importance as a heritable risk factor for IC-mediated renal injury in Brazilian lupus patients.