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PMID: 8636449 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans.

The Journal of clinical investigation ·Vol. 97 ·No. 5 ·1996-03-01 ·Pages 1348-54

Salmon JE, Millard S, Schachter LA, Arnett FC, Ginzler EM, Gourley MF, Ramsey-Goldman R, Peterson MG, Kimberly RP

Abstract

Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma 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 gamma 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 gamma 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 gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene. The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans.

MeSH Terms
Alleles Blacks/genetics Humans Lupus Erythematosus, Systemic/genetics Lupus Nephritis/etiology,genetics Pilot Projects Receptors, IgG/genetics,physiology Risk Factors
Chemicals
Receptors, IgG
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Salmon J E
Department of Medicine, Graduate Program in Immunology, The Cornell University Medical College, New York 10021, USA.
Millard S
Schachter L A
Arnett F C
Ginzler E M
Gourley M F
Ramsey-Goldman R
Peterson M G
Kimberly R P
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118552
Published
1996-03-01
Pages
1348-54
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507190
Subset
IM
Grants
NIAMS NIH HHS · P50-AR42588 · United States
NIAMS NIH HHS · R01-AR333062 · United States
NIAMS NIH HHS · R01-AR38889 · United States
External Links
PubMed source DOI: 10.1172/JCI118552 PMC Full Text View journal details
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