Association of Killer Cell Immunoglobulin- Like Receptor Genes in Iranian Patients With Rheumatoid Arthritis Publisher Pubmed



Nazari M^{1, 2} ; Mahmoudi M² ; Rahmani F^{2, 3, 4} ; Akhlaghi M² ; Beigy M^{2, 3, 4} ; Azarian M² ; Shamsian E² ; Akhtari M² ; Mansouri R^{1, 5} Show Affiliations
Source: PLoS ONE Published:2015

Abstract

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 I‡A 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. © 2015 Nazari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.