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

Background. Fc gamma receptors (Fc gamma Rs) 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 Fc gamma R polymorphisms (Fc gamma RIIa, Fc gamma RIIIa and Fc gamma RIIIb) that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the present study was to clarify whether Fc gamma R 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 Fc gamma R polymorphisms (Fc gamma RIIa-131H or R, Fc gamma RIIIa-176F or V and Fc gamma RIIIb-NA1 or -NA2). The genotyping of these polymorphisms was performed using allele-specific polymerase chain reaction (PCR) methods. Associations among Fc gamma R polymorphisms and susceptibility, age of onset, levels of serum immunoglobulins, intensity of glomerular IgG deposition and pathological severity were analysed. Results. These three Fc gamma R polymorphisms showed no significant differences in genotype and allele frequencies between the IgAN patients and healthy controls. Each Fc gamma R polymorphism had no influence on age of onset, serum levels of IgG and glomerular IgG deposition in IgAN. However, Fc gamma RIIa-131R (R/R or H/R) or Fc gamma RIIIa-176V homozygous carriers (V/V) showed significantly more severe injury than Fc gamma RIIa-131H homozygous (H/H) (P < 0.03) or Fc gamma RIIIa-176F carriers (F/F or F/V) (P < 0.03), respectively. Conclusion. The present study shows that polymorphisms of Fc gamma RIIa and Fc gamma RIIIa 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 Fc gamma Rs.