Polymorphisms of KIR Gene and HLA-C Alleles: Possible Association with Susceptibility to HLA-B27-Positive Patients with Ankylosing Spondylitis
Polymorphisms of KIR Gene and HLA-C Alleles: Possible Association with Susceptibility to HLA-B27-Positive Patients with Ankylosing Spondylitis
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DOI：
10.1007/s10875-010-9444-z
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发表时间：
2010-11-01
影响因子：
9.1
通讯作者：
Zhao, Yue-Ran
中科院分区：
文献类型：
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作者：
Jiao, Yu-Lian;Zhang, Bing-Chang;Zhao, Yue-Ran
越来越多的证据表明，杀伤细胞免疫球蛋白样受体（KIR）及其相应的特异性HLA-C配体通过调节自然杀伤（NK）细胞和T细胞的功能参与多种自身免疫性疾病的发病。本研究旨在探讨KIR基因和HLA配体多态性与强直性脊柱炎（AS）易感性的关系。已有研究表明HLA-B27基因与AS发病密切相关。在这项研究中，招募了115名无关的HLA-B27阳性AS患者和119名HLA-B27阳性健康对照。采用序列特异性引物聚合酶链反应检测KIR基因和HLA-C等位基因的基因型。结果显示，KIR 2DL 1和KIR 2DL 5在AS患者组中的频率显著高于对照组（分别为p=0.012和p=0.009）。同时，AS患者HLA-Cw*08频率较对照组增高（p=0.001，p（c）=0.008）。提示在HLA-B27的遗传背景下，KIR及其相应的特异性HLA-C配体的变异可能影响NK细胞和T细胞识别和裂解免疫应答中靶点的能力，从而参与AS的发病。
Accumulating evidences indicate that killer cell immunoglobulin-like receptors (KIRs) and their corresponding specific HLA-C ligands contribute to the pathogenesis of multiple autoimmune diseases via the modulation of natural killer (NK) cell and T cell functions. The present study was performed to investigate whether the polymorphism of KIR genes and HLA ligands associates with the susceptibility of ankylosing spondylitis (AS). Previous studies have demonstrated a strong association between HLA-B27 gene and the pathogenesis of AS. In this study, 115 unrelated HLA-B27-positive AS patients and 119 HLA-B27-positive healthy controls were recruited. Polymerase chain reaction using sequence-specific primers was used to determine the genotypes of KIR genes and HLA-C alleles. The results showed that the frequencies of KIR2DL1 and KIR2DL5 were significantly higher in the AS patient group than those in the control group (p=0.012 and p=0.009, respectively). Meanwhile, individuals with AS showed an increased frequency of HLA-Cw*08 (p=0.001, p(c)=0.008) compared with that in controls. Our findings indicate that with the genetic background of HLA-B27, variation at the KIRs and their corresponding specific HLA-C ligands may influence the ability of NK cells and T cells to recognize and lyse targets in immune responses, which thereby contributes to pathogenesis of AS.