1. Killer Cell Immunoglobulin-Like Receptor Genes and their HLA-C Ligands in Hashimoto Thyroiditis in a Chinese Population
- Author
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Yong-qing Wei, Gui-na Yu, Jin Xu, Yan-feng Hou, Hui Sun, Yulian Jiao, Ming-feng Cao, Yiqing Liu, Jiajun Zhao, Yueran Zhao, Jian-ting Li, Cheng Guo, Li Feng, Haiqing Zhang, Minglong Li, Bingchang Zhang, and Ling Gao
- Subjects
Adult ,Male ,0301 basic medicine ,China ,Endocrinology, Diabetes and Metabolism ,Killer-cell immunoglobulin-like receptor ,HLA-C Antigens ,Hashimoto Disease ,Human leukocyte antigen ,Ligands ,law.invention ,03 medical and health sciences ,HLA-C ,0302 clinical medicine ,Endocrinology ,Asian People ,Gene Frequency ,Receptors, KIR ,law ,Genotype ,Humans ,Medicine ,Genetic Predisposition to Disease ,Receptor ,Allele frequency ,Polymerase chain reaction ,business.industry ,General Medicine ,Middle Aged ,030104 developmental biology ,Case-Control Studies ,Immunology ,Female ,business ,030215 immunology - Abstract
Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis.The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels.Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001).Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases.HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.
- Published
- 2016