ROLE OF NK CELL RECEPTORS IN SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS.
DP Singal, J Li, G Zhang, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

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Human NK cells use molecules of the immunoglobulin superfamily called the killer cell inhibitory receptors (KIRs) as their HLA class I receptors. Since the KIRs have opposing effects on signal transduction pathways and effector function, it is likely that polymorphisms in KIR genes play an important role in development of autoimmune diseases, including rheumatoid arthritis (RA). We therefore compared the prevalence of KIRs responsible for inhibitory functions (2DL1, 2DL2, 2DL3, 3DL1 and 3DL2) and for activating signals (2DS1, 2DS2, 2DS3, 2DS4, 2DS5 and 3DS1) in patients with classical seropositive RA with those in normal healthy controls. The results show that the prevalence of inhibitory KIR 3DL1 was higher in RA patients as compared to normal controls in total and RA susceptibility DRB1 epitope-positive groups. In addition, the prevalence of noninhibitory 2DS2 was higher in RA susceptibility DRB1 epitope-negative patients than in the respective group of normal individuals. The data also demonstrate that significantly different proportions of patients carried 4and 5 inhibitory KIRs as well as 4 and 5 noninhibitory KIRs. It is likely that the higher prevalence of HLA-B- specific inhibitory K1R 3DL1 in total and RA susceptibility epitope-positive patients, and of HLA-C group I -specific K1R 2DS2 in RA susceptibility epitope-negative patients effect NK cell function and cause susceptibility to RA. Similarly, differences in the expression of number of inhibitory and noninhibitory KIRs may cause imbalance in immune response and result in development of RA.