Association of killer cell immunoglobulin-like receptor genotypes with microscopic polyangiitis.
Association of killer cell immunoglobulin-like receptor genotypes with microscopic polyangiitis.
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DOI：
10.1002/art.21653
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发表时间：
2006-03
影响因子：
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通讯作者：
R. Miyashita;N. Tsuchiya;T. Yabe;Shigeto Kobayashi;H. Hashimoto;S. Ozaki;K. Tokunaga
中科院分区：
文献类型：
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作者：
R. Miyashita;N. Tsuchiya;T. Yabe;Shigeto Kobayashi;H. Hashimoto;S. Ozaki;K. Tokunaga
目的：遗传背景和感染与显微镜下多血管炎（MPA）的病因有关。杀伤细胞免疫球蛋白样受体（KIRs）是一类表达于自然杀伤细胞（NK）和T细胞上的激活和抑制受体，其基因具有极端的多态性。一些KIR与HLA I类亚群结合，KIR基因与其配体HLA之间的遗传相互作用已被证明与几种自身免疫性和病毒性疾病有关。在这项研究中，我们研究了KIR位点的存在或缺失与MPA遗传易感性的可能关联。方法对57例骨髓过氧化物酶抗中性粒细胞胞浆抗体阳性的日本受试者（43例MPA患者和239例健康对照）进行14个KIR位点的检测。结果与健康对照组相比，MPA患者KIR2DS3的携带者激活频率显著降低（4.7% vs . 16.7%; P = 0.038，优势比[OR] 0.24, 95%可信区间[95% CI] 0.06-0.94）。当将KIRs与其HLA配体联合分析时，与对照组相比，MPA组携带抑制性KIR3DL1和HLA- bw4但不激活受体KIR3DS1的个体比例显著增加（46.5%比27.0%;P = 0.014, OR 2.35, 95% CI 1.18-4.70）。此外，当受试者根据KIR3DL1/3DS1/HLA-B和KIR2DL1/ HLA-C组合进行分类时，观察到随着组合的抑制作用越来越强，敏感性呈增加趋势。结论KIR/HLA基因型相关的NK和/或T细胞活化电位降低可能导致MPA易感，可能是由于抗感染能力不足所致。
OBJECTIVE Genetic background and infection have been implicated in the etiology of microscopic polyangiitis (MPA). Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to HLA class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune and viral diseases. In this study, we examined possible associations of the presence or absence of KIR loci with a genetic predisposition to MPA. METHODS The presence or absence of 14 KIR loci was determined in 57 myeloperoxidase antineutrophil cytoplasmic antibody-positive Japanese subjects (43 patients with MPA and 239 healthy controls). RESULTS The carrier frequency of activating KIR2DS3 was significantly decreased among patients with MPA compared with healthy controls (4.7% versus 16.7%; P = 0.038, odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.06-0.94). When KIRs were analyzed in combination with their HLA ligands, the proportion of individuals carrying inhibitory KIR3DL1 and HLA-Bw4 but not activating receptor KIR3DS1, a combination presumed to be the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in the MPA group compared with the control group (46.5% versus 27.0%; P = 0.014, OR 2.35, 95% CI 1.18-4.70). Furthermore, when subjects were classified according to KIR3DL1/3DS1/HLA-B and KIR2DL1/ HLA-C combinations, an increasing trend toward susceptibility was observed as combinations became more inhibitory. CONCLUSION The decreased activation potential of NK and/or T cells associated with KIR/HLA genotypes may predispose to MPA, possibly through insufficient resistance against infections.