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NDT Advance Access published online on March 5, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh121
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received August 21, 2003
Accepted December 17, 2003

Original Papers

Fc{gamma}RIIa polymorphism: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients

Ana Paula Bazilio 1, Vilma S. T. Viana 1, Rui Toledo 2, Viktoria Woronik 2, Eloisa Bonfá 1, Renato C. Monteiro 3*

1 Division of Rheumatology, University of São Paulo, São Paulo, Brazil
2 Division of Nephrology, University of São Paulo, São Paulo, Brazil
3 INSERM E-0225, Bichat Medical School, Paris, France

* To whom correspondence should be addressed. E-mail: monteiro{at}bichat.inserm.fr.



  Abstract

Background. Fc{gamma}RIIa is a low affinity receptor that has two co-dominantly expressed alleles, R131 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 R131 variant. The Fc{gamma}RIIa polymorphism has been shown to be associated with lupus nephritis. Here we evaluated the relevance of Fc{gamma}RIIa 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. Fc{gamma}RIIa genotyping was performed by PCR with allele-specific primers to distinguish between the two allelic forms (H131 and R131).

Results. Comparison of Fc{gamma}RIIa genotypes distribution in SLE patients with nephritis and in controls showed a significant increase in Fc{gamma}RIIa-R131 homozygosity (P <= 0.02). The genotype distribution in lupus nephritis (45% with Fc{gamma}RIIa-R/R131, 30% with H/R131 and 25% with H/H131) was distinct from that observed in controls (21% with Fc{gamma}RIIa-R/R131, 52% with H/R131 and 27% with H/H131). In contrast, there was no difference in the distribution of Fc{gamma}RIIa genotypes in lupus without nephritis and controls (P = 0.3). Reinforcing the relevance of Fc{gamma}RIIa polymorphism in IC-mediated nephritis, patients with renal failure had an over-representation of the R131 allele (70%) when compared with normal controls (47%) (P = 0.06).

Conclusions. The skewed distribution of Fc{gamma}RIIa 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.

Keywords: autoimmunity, Fc receptors, glomerulonephritis, immunoglobulin, systemic lupus erythematosus


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