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Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis

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Abstract

Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: “KIR3DL1; HLA-BW4-Thr80” and “KIR3DL1 -HLA-BW4-A1.” None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition.

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Acknowledgements

This survey was supported by grants from the research deputy of Tehran university of Medical Sciences (92-01-41-2150) and Qom university of Medical Sciences. This study was approved by the ethics committee of Tehran University of Medical Sciences, The approval number of the ethics committee is IR.TUMS.REC.1395.2804.

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Authors and Affiliations

  1. Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave,, P.o. box: 1411713137, Tehran, Iran

    Mahdi Mahmoudi, Soheila Sobhani, Shima Ghoroghi, Ahmadreza Jamshidi, Shiva Poursani, Zahra Hosseinpour & Farhad Gharibdoost

  2. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

    Faranak Fallahian & Masoumeh Dolati

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  1. Mahdi Mahmoudi
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  2. Faranak Fallahian
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  4. Shima Ghoroghi
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Correspondence to Mahdi Mahmoudi or Farhad Gharibdoost.

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Faranak Fallahian is co-first author.

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Mahmoudi, M., Fallahian, F., Sobhani, S. et al. Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis. Clin Rheumatol 36, 853–862 (2017). https://doi.org/10.1007/s10067-016-3526-0

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