Fcgamma receptor polymorphisms in systemic lupus erythematosus: association with disease and in vivo clearance of immune complexes.

Abstract

OBJECTIVE:

Fc receptors for IgG (FcgammaR) play a prominent role in the clearance of immune complexes in systemic lupus erythematosus (SLE). Polymorphisms of FcgammaR have been proposed as genetic factors that influence susceptibility to SLE. We analyzed 3 functional FcgammaR polymorphisms in a strictly Caucasian population of SLE patients, and determined the influence of these polymorphisms on the clearance of immune complexes in vivo.

METHODS:

Genomic DNA was isolated from 230 Caucasian patients with SLE and 154 controls. Amplification of FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. In addition, we analyzed the FcgammaR genotypes of 13 patients with SLE who participated in a study determining the half-life of IgG-coated erythrocytes in the blood.

RESULTS:

We found a strong trend toward skewing of FcgammaRIIa, with an enrichment of the homozygous FcgammaRIIa-R/R131 genotype in patients compared with controls. We did not find a correlation between this genotype and the development of lupus nephritis. However, we established that the half-life of IgG-coated erythrocytes in the blood was prolonged in patients expressing the FcgammaRIIa-R/R131 genotype. The homozygous FcgammaRIIIa-F/F158 genotype was found more frequently in patients with arthritis and/or serositis.

CONCLUSION:

In Caucasian populations, the R/H polymorphism of FcgammaRIIa is a minor determinant in susceptibility to SLE, whereas the V/F polymorphism of FcgammaRIIIa is associated with a set of disease manifestations. Notably, the R/H polymorphism of FcgammaRIIa affects the clearance of immune complexes in vivo, which may influence the course of a disease such as SLE.

• Authors: H M Dijstelbloem, M Bijl, R Fijnheer, R H Scheepers, W W Oost, M D Jansen, W J Sluiter, P C Limburg, R H Derksen, J G van de Winkel, C G Kallenberg
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 43 Issue 12 Pg. 2793-800 (Dec 2000) ISSN: 0004-3591 [Print] United States
• PMID: 11145038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigen-Antibody Complex
• Receptors, IgG

Topics

• Adolescent
• Adult
• Aged
• Antigen-Antibody Complex (metabolism)
• Child
• Female
• Genotype
• Half-Life
• Humans
• Lupus Erythematosus, Systemic (blood, genetics)
• Lupus Nephritis (genetics)
• Male
• Middle Aged
• Polymorphism, Genetic
• Receptors, IgG (genetics)