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


CONCLUSIONS
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.
Dijstelbloem
H M
HM
University Hospital Groningen, The Netherlands.
Bijl
M
M
Fijnheer
R
R
Scheepers
R H
RH
Oost
W W
WW
Jansen
M D
MD
Sluiter
W J
WJ
Limburg
P C
PC
Derksen
R H
RH
van de Winkel
J G
JG
Kallenberg
C G
CG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000378:metabolism; D002648:Child; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*
D000936:Antigen-Antibody Complex; D017452:Receptors, IgG