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Polymorphism of killer cell immunoglobulin-like receptors (KIR) and their HLA ligands in Graves’ disease

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Abstract

Killer immunoglobulin-like receptors (KIR) play a pivotal role in commencement of both innate and adaptive immunity. Dysregulation of KIRs is associated with an increased risk of autoimmune disorders. This study was designed to assess whether polymorphisms in KIR gene family and their respective HLA class I ligands confer protection or susceptibly to Graves’ disease (GD). Eighty patients with confirmed GD (cases) and 176 healthy unrelated subjects (controls) were recruited. Using a polymerase chain reaction sequence-specific primer directed method (PCR-SSP), presence or absence of KIR genes and their HLA ligands were determined. No significant differences were observed between case and control groups regarding individual KIR gene frequencies (p > 0.05 in all cases). The frequency of group A haplotype (the most common KIR haplotype, encompassing 2DL1/2DL3/3DL1/2DS4/2DP1/3DP1/2DL4/3DL2/3DL3), was not different between individuals with and without GD. Moreover, among all other haplotypes (group Bx), no significant differences regarding distribution of centromeric and telomeric gene clusters were identifiable. Inhibitory/activatory gene contents were also comparable between the two groups. Four models of KIR-HLA interaction (inhibition, activation, unrestrained inhibition, and unrestrained activation) were constructed. No combination proved to confer susceptibility to, or offer protection against GD. It seems that the contribution of KIR gene polymorphism to natural killer cell dysfunction and other autoimmune abnormalities observed in GD is limited.

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Acknowledgments

This study was financially supported by the research deputy of Tehran University of Medical Sciences (Grant number: 12087).

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The authors report no conflicts of interest

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish Island, Iran

    Romina Dastmalchi & Ali Farazmand

  2. Department of Cellular and Molecular Biology, Faculty of Science, University of Tehran, Tehran, Iran

    Ali Farazmand

  3. Molecular Immunology Research Center and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Keshavarz Boulevard, Poursina Street, 14161351, Tehran, Iran

    Sina Noshad, Mohamad Mozafari & Aliakbar Amirzargar

  4. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Sina Noshad, Mohamad Mozafari & Alireza Esteghamati

  5. Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Mahdi Mahmoudi

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  1. Romina Dastmalchi
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Correspondence to Aliakbar Amirzargar.

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Dastmalchi, R., Farazmand, A., Noshad, S. et al. Polymorphism of killer cell immunoglobulin-like receptors (KIR) and their HLA ligands in Graves’ disease. Mol Biol Rep 41, 5367–5374 (2014). https://doi.org/10.1007/s11033-014-3408-y

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  • DOI: https://doi.org/10.1007/s11033-014-3408-y

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