Rheumatoid arthritis is associated with KIR2DS4-full among the KIR genes in Lur Population of Iran

Mehdi Birjandi,Ali Sheikhian,Seyyed Amir Yasin Ahmadi,Hamzeh Ali Torang,Nazanin Mousavi,Farhad Shahsavar,Ali Asghar Kiani,Bijan Ansari-Moghaddam

doi:10.52547/rbmb.10.1.84

Abstract

The pathophysiology underlying the progression and development of autoimmune conditions, such as Rheumatoid Arthritis (RA), is a result of dysregulations of the immune system. Research has explored the genetic alterations present in RA; however, limited studies have examined the role of Killer cell Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) molecules in RA. Therefore, the aim of this study was to examine KIR genes, their HLA ligands, and KIR-HLA compounds in patients with RA.In this case-control study, a total of 50 patients with RA and 100 healthy individuals were enrolled. DNA samples were evaluated using PCR with sequence specific Primers (PCR-SSP). Odds ratio (OR) with a 95% confidence interval (CI) were reported.Among the KIR genes examined, KIR2DLA (p= 0.0255, OR= 0.389, 95% CI= 0.210-0.722) and KIR2DS4-full (p< 0.0001, OR= 6.163, 95% CI= 3.174-11.968) were observed to have a statistically significant correlation with disease susceptibility to RA. As an inhibitory gene, KIR2DLA was observed to have a protective effect against RA while KIR2DS4-full as an activating gene, was found to increase risk for RA. No significant associations were found between any of the other KIR genotypes, HLA ligands, or KIR-HLA compounds examined in this study to RA susceptibility.In this study of RA in the Lur population of Iran, KIR2DS4-full was observed to increase susceptibility to RA, while KIR2DL5A was found to act as a protecting factor based on both the cross Table and regression analyses. Further research should focus on repeating this study in additional populations.

Highlights

Rheumatoid Arthritis (RA) is a common chronic autoimmune disorder characterized by synovitis, chronic hyperplasia, bone erosion, progressive joint damage, irreversible loss of bone shape and mobility problems (1, 2)
Our findings show that the inhibitor gene, KIR2DL5A (p= 0.0255, Odds ratio (OR)= 0.389, 95% confidence interval (CI)= 0.210-0.722), and the activating gene, KIR2DS4-full
Our findings show that KIR2DS4-full exhibited the strongest risk association with RA (p< 0.001, adjusted OR= 18.531, 95% CI= 5.453-62.972) followed by KIR2DS4-del (p= 0.034, adjusted OR= 3.894, 95% CI= 1.107-13.690)

Summary

Introduction

Rheumatoid Arthritis (RA) is a common chronic autoimmune disorder characterized by synovitis, chronic hyperplasia, bone erosion, progressive joint damage, irreversible loss of bone shape and mobility problems (1, 2). Human leukocyte antigen (HLA)-DR appears to hold the most significant role among the potential predisposing genetic factors for RA as the example of a gene cluster associated with ethnicities. Research has explored the genetic alterations present in RA; limited studies have examined the role of Killer cell Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) molecules in RA. Results: Among the KIR genes examined, KIR2DLA (p= 0.0255, OR= 0.389, 95% CI= 0.210-0.722) and KIR2DS4-full (p< 0.0001, OR= 6.163, 95% CI= 3.174-11.968) were observed to have a statistically significant correlation with disease susceptibility to RA. Conclusions: In this study of RA in the Lur population of Iran, KIR2DS4-full was observed to increase susceptibility to RA, while KIR2DL5A was found to act as a protecting factor based on both the cross Table and regression analyses. Further research should focus on repeating this study in additional populations

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