Association between SLE nephritis and polymorphic variants of the CRP and Fc RIIIa genes

Abstract

To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding FcgammaRIIa, FcgammaRIIIa, FcgammaRIIIb, CRP and IL-1Ra. Genetic polymorphisms were analysed in 323 unrelated SLE patients and 200 healthy blood donors. The genotype frequencies were compared between clinical subsets of SLE patients, as well as with healthy controls. Clinical manifestations included the ACR classification criteria. Nephritis was further classified according to WHO class on renal biopsy. Presence of a CRP4 A-allele was associated with SLE nephritis (P < 0.01) and inversely correlated with arthritis (P < 0.01), when comparing within the SLE group. The FcgammaRIIIa F/F genotype was also associated with nephritis (WHO class III and IV, P = 0.04 for the SLE group) and in combination with the CRP4 A-allele a stronger association was noted (P < 0.001). Furthermore, the FcgammaRIIIb NA2/NA2 genotype was associated with butterfly rash (P < 0.01). An association was found between seizures and the presence of both the FcgammaRIIa R/R and the FcgammaRIIIa F/F genotypes (P < 0.01) and an inverse correlation between serositis and the CRP4 A-allele when present together with the IL-1Ra 2-allele (P = 0.01). Furthermore, a combination of the FcgammaRIIa R/R genotype and CRP4 A-allele was associated with lymphopenia (P = 0.02) and a similar result was found for the combination of FcgammaRIIIa F/F and FcgammaRIIIb NA2/NA2 (P = 0.04). Polymorphic variants of the CRP and Fcgamma-receptor genes are associated with the clinical phenotype in SLE. Our findings suggest an immune complex-mediated pathogenesis in nephritis and seizures, while development of arthritis may depend on other pathogenetic pathways.