Killer cell immunoglobulin-like receptor genes in Spanish multiple sclerosis patients
Killer cell immunoglobulin-like receptor genes in Spanish multiple sclerosis patients
复制标题
DOI：
10.1016/j.molimm.2011.05.018
复制
发表时间：
2011-09-01
影响因子：
3.6
通讯作者：
Leyva-Fernandez, Laura
中科院分区：
文献类型：
--
作者：
Garcia-Leon, Juan A.;Pinto-Medel, Maria J.;Leyva-Fernandez, Laura
杀伤细胞免疫球蛋白样受体（KIR）是通过与人白细胞抗原（HLA）I类配体相互作用来调节自然杀伤细胞和某些T细胞的细胞溶解活性的调节剂。KIR已被证明有助于几种自身免疫性疾病的发病机制，但其在多发性硬化症（MS）中的作用仍不清楚。在这里，我们确定了KIR基因和他们的HLA I类配体对MS的易感性和对干扰素β治疗的西班牙人口的影响。对200例MS患者和200例对照者进行KIR和HLA基因分型。在MS患者中发现KIR 2DL 5和KIR 3DS 1基因的频率显著较高，并且KIR 2DL 1基因的携带与较高的进展指数相关。此外，MS患者中HL 4-Bw 4基序的频率显著降低。KIR 2DL 1和HLA-C2匹配在MS患者中更常见，而KIR 3DL 1和HLA-Bw 4匹配在健康对照中更常见。然而，所有KIR基因与干扰素β治疗反应之间无显著相关性。我们的研究结果证实，携带HL 4-Bw 4是MS的保护因子，并建议KIR 2DL 5和KIR 3DS 1可能在疾病中具有易感作用。(C)2011爱思唯尔有限公司保留所有权利。
Killer cell immunoglobulin-like receptors (KIRs) are regulators of cytolytic activity of natural killer and certain T cells through interactions with human leukocyte antigen (HLA) class I ligands. KIRs have been shown to contribute to the pathogenesis of several autoimmune diseases, but their role in multiple sclerosis (MS) is still unclear. Here we determined the influence of KIR genes and their HLA class I ligands on susceptibility to MS and on the response to interferon-beta treatment in a Spanish population. KIR and HLA genotyping were performed in 200 MS patients and 200 controls. Significantly higher frequencies were found for KIR2DL5 and KIR3DS1 genes in MS patients and the carriage of the KIR2DL1 gene was associated with a higher progression index. Moreover, the frequency of the HL4-Bw4 motif was significantly reduced in MS patients. The KIR2DL1 and HLA-C2 matches were more frequent in MS patients, whereas the KIR3DL1 and HLA-Bw4 matches were more frequent in healthy controls. Nevertheless, non significant associations were found between all the KIR genes and therapeutic response to interferon-beta. Our results confirm that the carriage of HL4-Bw4 is a protective factor in MS and suggest that KIR2DL5 and KIR3DS1 may have a predisposing role in the disease. (C) 2011 Elsevier Ltd. All rights reserved.