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Nephrology Dialysis Transplantation 2005 20(11):2439-2445; doi:10.1093/ndt/gfi043
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Article

Fc{gamma}RIIa-131R allele and Fc{gamma}RIIIa-176V/V genotype are risk factors for progression of IgA nephropathy

Yuichi Tanaka1, Yusuke Suzuki1, Toshinao Tsuge1,2, Yutaka Kanamaru1,2, Satoshi Horikoshi1, Renato C. Monteiro2 and Yasuhiko Tomino1

1 Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan and 2 Department of Immunopathology, Bicht Medical School, INSERM E0225, Paris, France

Correspondence and offprint requests to: Yasuhiko Tomino, MD, Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Email: yasu{at}med.juntendo.ac.jp

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.

Keywords: Fc{gamma} receptor; IgA nephropathy; IgG; polymorphism


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