Immunoglobulin G fc-receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms related to disease severity in rheumatoid arthritis.
OBJECTIVE
Fc receptors for IgG (FcyR) modulate immune responses. FcyR are expressed on various leukocytes and contain allelic polymorphisms with different capacity for IgG binding and phagocytosis. We investigated the distribution of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB polymorphisms in rheumatoid arthritis (RA) and whether they were related to disease expression and severity.


METHODS
Ninety-six controls and 114 patients fulfilling American College of Rheumatology (ACR) criteria for RA were genotyped for FcgammaRIIA, IIIA, and IIIB using polymerase chain reaction. Physician's global assessment of RA type estimated RA disease expression. In addition, usual measures of disease activity were recorded.


RESULTS
The genotype and allele frequencies did not differ significantly between the RA patients and the controls. Patients homo or heterozygous for the FcgammaRIIA arginine (R) allele had significantly more aggressive RA and swollen joints than patients homozygous for the FcgammaRIIA histidine (H) allele. Although there was a tendency of more severe disease among patients homo or heterozygous for the FcgammaRIIIA valine allele, there were no significant findings with the disease activity for the FcgammaRIIIA and FcgammaRIIIB genotypes.


CONCLUSIONS
FcgammaRIIA is implicated as a possible disease modifying gene in RA. Individuals homozygous for the FcgammaRIIA R allele have less efficient binding of IgG2 subclasses than individuals homozygous for the H allele. Less effective processing of circulating immune complexes in RA patients homozygous for the FcgammaRIIA R allele may therefore contribute to a more unfavorable course.
Brun
Johan G
JG
Department of Rheumatology, Haukeland University Hospital, Bergen, Norway. jgbr@haukeland.no
Madland
Tor M
TM
Vedeler
Christian A
CA
D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D011961:Receptors, Fc / Q000235:genetics* / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D005819:Genetic Markers; D011961:Receptors, Fc; D017452:Receptors, IgG