Fc gamma R expression on NK cells influences disease severity in rheumatoid arthritis.
Rheumatoid arthritis (RA) is associated with autoantibodies, the best known of which is rheumatoid factor (RF). RF/IgG complexes interact with FcgammaR on the surface of neutrophils, NK cells and monocyte/macrophages. We have analyzed the expression pattern and allelic polymorphisms of three FcgammaR genes (FcgammaRIIA, FcgammaRIIC and FcgammaRIIIA) in a large sample of RA patients and normal donors. We have found that the level of FcgammaR (CD16 and CD32) expression on NK cells is lower in RA patients than in normal individuals. Genotypic analysis demonstrated that the CD32 isoform expressed by the majority of RA patients was not the activating FcgammaRIIc1 isoform, commonly seen in normal individuals, but rather the inhibitory FcgammaRIIb isoform. The combination of the FcgammaRIIIA-176F allele with a lack of CD32 expression in NK cells appeared to be characteristic of RA subjects with aggressive disease. Since FcgammaRII and FcgammaRIIIA are predominantly expressed by NK cells, these data further suggest that FcgammaR-mediated activation of NK cells could be a disease-determining factor in RA patients.
Stewart-Akers
A M
AM
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Cunningham
A
A
Wasko
M C
MC
Morel
P A
PA
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics; D012720:Severity of Illness Index
D015703:Antigens, CD; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG