Abstract
ObjectivesRheumatoid 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 І genes as their corresponding ligands in RA patients and control subjects.MethodsIn 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 χ² 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.ConclusionIndividuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.
Highlights
KIR2DL2, 2DL5a, 2DL5b and activating Killer Cell Immunoglobulin- Like Receptors (KIR): KIR2DS5 and 3DS1 were all protective against Rheumatoid Arthritis (RA)
Rheumatoid Arthritis (RA) is a chronic auto-inflammatory disorder of the joints and articular surfaces characterized by persistent synovitis and synovial hyperplasia which leads to destruction of bone and cartilage deformity [1, 2]
We investigated the presence of 16 KIR genes and 3 pseudogenes and 6 of the confirmed HLA ligands as well as their interactions to provide the first information about possible associations between the KIR and HLA genotype profile with rheumatoid arthritis susceptibility in the Iranian population
Summary
Rheumatoid Arthritis (RA) is a chronic auto-inflammatory disorder of the joints and articular surfaces characterized by persistent synovitis and synovial hyperplasia which leads to destruction of bone and cartilage deformity [1, 2]. The prevalence of RA is higher in women compared to men [3]. RA shows different patterns of etiology among populations. The core of each pattern is the individual’s genetic predisposition to the disease and its interaction with environmental triggers. Genetic factors comprise about 60% of the disease etiology [4, 5]. Of all confirmed susceptibility loci for RA, HLA-DRB1, PTPN22, CD40, CTLA4 and genes coding elements of NFκB signaling pathway like TNFAIP3 and TRAF1 are the most important genetic risk factors for RA [6]
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