Objectives Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by persistent synovitis, ultimately leading to cartilage and bone degeneration. Natural Killer cells and CD28 null T-cells are suspected as role players in RA pathogenesis. These cells are similar in feature and function, as they both exert their cytotoxic effect via Killer Cell Immunoglobulin- Like Receptors (KIR) on their surface. KIR genes have either an inhibitory or activating effect depending on their intracytoplasmic structure. Herein we genotyped 16 KIR genes, 3 pseudo genes and 6 HLA class † genes as their corresponding ligands in RA patients and control subjects. Methods In this case-control study, KIR and HLA genes were genotyped in 400 RA patients and 372 matched healthy controls using sequence-specific primers (SSP-PCR). Differences in the frequency of genes and haplotypes were determined by Ï‡Â test. Results KIR2DL2, 2DL5a, 2DL5b and activating KIR: KIR2DS5 and 3DS1 were all protective against RA. KIR2DL5 removal from a full Inhibitory KIR haplotype converted the mild protection (OR = 0.56) to a powerful predisposition to RA (OR = 16.47). Inhibitory haplotype No. 7 comprising KIR2DL5 in the absence of KIR2DL1 and KIR2DL3 confers a 14-fold protective effect against RA. Conclusion Individuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.
Nazari, M., Mahmoudi, M., Rahmani, F., Akhlaghi, M., Beigy, M., Azarian, M., … Mansouri, R. (2015). Association of killer cell immunoglobulin- like receptor genes in iranian patients with rheumatoid arthritis. PLoS ONE, 10(12). https://doi.org/10.1371/journal.pone.0143757