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Rapid Publication Fc g RIIA Alleles Are Heritable Risk Factors for Lupus Nephritis in African Americans
9 auth. J. Salmon, S. Millard, Leah A. Schachter, F. Arnett, E. Ginzler, M. Gourley, ...
Allelic variants of Fc g R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc g RIIa has two codomi-nantly expressed alleles, R131 and H131, which differ substantially in thei…
Allelic variants of Fc g R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc g RIIa has two codomi-nantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc g RIIa-H131 is the only human Fc g R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc g RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc g RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc g RIIA alleles, with only 9% of SLE patients homozygous for Fc g RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05–0.69, P 5 0.009). This was confirmed with a multi-center study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc g RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc g RIIA-H131 as the likelihood for lupus nephritis increased ( P 5 0.0004) consistent with a protective effect of the Fc g RIIA-H131 gene. The skewing in the distribution of Fc g RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans. ( J. Clin. Invest. 1996. 97:1348–1354.)
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6
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4 | 1996 |
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