FcγRIIa-131R allele and FcγRIIIa-176V/V genotype are risk factors for progression of IgA nephropathy

Abstract

Background. Fcγ receptors (FcγRs) may play an important role in positive and negative regulation of immune cell responses and immune complex (IC) clearance. Mesangial IgG deposition and circulating IgG/IgA-IC in sera are observed in patients with IgA nephropathy (IgAN). Therefore, the pathological roles of IgG-IC in IgAN have been discussed. On the other hand, several studies have identified FcγR polymorphisms (FcγRIIa, FcγRIIIa and FcγRIIIb) that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the present study was to clarify whether FcγR polymorphisms influence susceptibility to IgAN, clinical features or severity in patients with IgAN. Methods. Japanese patients with IgAN (n = 124) and healthy controls (n = 100) were genotyped for FcγR polymorphisms (FcγRIIa-131H or R, FcγRIIIa-176F or V and FcγRIIIb-NA1 or -NA2). The genotyping of these polymorphisms was performed using allele-specific polymerase chain reaction (PCR) methods. Associations among FcγR polymorphisms and susceptibility, age of onset, levels of serum immunoglobulins, intensity of glomerular IgG deposition and pathological severity were analysed. Results. These three FcγR polymorphisms showed no significant differences in genotype and allele frequencies between the IgAN patients and healthy controls. Each FcγR polymorphism had no influence on age of onset, serum levels of IgG and glomerular IgG deposition in IgAN. However, FcγRIIa-131R (R/R or H/R) or FcγRIIIa-176V homozygous carriers (V/V) showed significantly more severe injury than FcγRIIa-131H homozygous (H/H) P<0.03) or FcγRIIIa-176F carriers (F/F or F/V) (P<0.03), respectively. Conclusion. The present study shows that polymorphisms of FcγRIIa and FcγRIIIa influence the severity of IgAN in Japanese patients but not the incidence, suggesting that IgG-IC may play important roles in the progression and prognosis of this disease via FcγRs. © The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.