Association of Killer Cell Immunoglobulin-like Receptor (KIR) Genes and  their HLA Ligands with Susceptibility to Takayasu Arteritis in the  Iranian Population

Fereshteh Beigmohammadi; Saeed Aslani; Hoda Kavosi; Ali Javinani; Shayan Mostafaei; Mehran Pournazari; Baharak Tasorian; Elham Farhadi; Asghar Hajiabbasi; Habib Zayeni; Alireza Khabbazi; Ahmadreza Jamshidi; Irandokht Shenavar Masooleh; Zahra Tamartash; Mahdi Vojdanian; Mahdi Mahmoudi

doi:10.18502/ijaai.v22i1.12003

Fereshteh Beigmohammadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Saeed Aslani Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Hoda Kavosi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Ali Javinani Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Shayan Mostafaei Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Mehran Pournazari Clinical Research Department Center, Imam Raza Hospital, Kermanshah University
Baharak Tasorian Division of Rheumatology, Department of Internal Medicine, Arak University of Medical Sciences, Arak, Iran
Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Asghar Hajiabbasi Department of Rheumatology, Guilan Rheumatology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
Habib Zayeni Department of Rheumatology, Guilan Rheumatology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
Alireza Khabbazi Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Ahmadreza Jamshidi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Irandokht Shenavar Masooleh Department of Rheumatology, Guilan Rheumatology Research Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
Zahra Tamartash Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Vojdanian Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v22i1.12003

Keywords: Genetic association; Killer cell immunoglobulin-like receptor; Natural killer cell; Takayasu arteritis

Abstract

Takayasu arteritis (TA) is a chronic inflammatory disorder characterized by vascular damage and fibrosis in the intima that commonly occurs in the aorta. In many damaged sites in TA patients, natural killer (NK) cells have been shown to be hyperactivated and produce inflammatory cytokines and toxic components. Killer cell immunoglobulin-like receptors (KIRs) are found on NK cells and interact with human leukocyte antigen (HLA) class I ligands to activate or suppress NK cells. The present study assessed the possible role of KIR and their HLA ligand genes in susceptibility to TA in Iranian patients.

This case-control study included 50 TA patients and 50 healthy subjects. DNA was extracted from whole peripheral blood samples, and polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed to recognize the presence or absence of polymorphism in 17 KIR genes and 5 HLA class I ligands in each participant.

Among the KIR and HLA genes, a significant decrease was detected in the frequency of
2DS4 (full allele) in TA patients (38%) compared with healthy controls (82%) (OR=0.13, 95%

CI=0.05–0.34). However, none of the KIR and HLA genotypes or the interactions between these genes were associated with susceptibility to TA.

The KIR2DS4 gene might be involved in the regulation of activation as well as the production of cytotoxic mediators of NK cells in patients with TA.