KIR in type 1 diabetes: Disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects
KIR in type 1 diabetes: Disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects
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DOI：
10.2337/diabetes.52.10.2639
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发表时间：
2003-10-01
期刊：
影响因子：
7.7
通讯作者：
Giphart, MJ
中科院分区：
文献类型：
--
作者：
van der Slik, AR;Koeleman, BPC;Giphart, MJ
杀伤细胞免疫球蛋白样受体（KIR）通过与靶细胞上的HLA 1类配体相互作用来调节自然杀伤细胞和T细胞功能。KIR和HLA都是高度多态性的。本研究探讨了KIR和HLA 1类基因对1型糖尿病易感性的影响。结果显示，与对照组相比，患者中激活KIR基因的数量增加（P = 0.049）。与糖尿病高危HLA配体匹配的对照受试者相比，患者中激活的KIR 2DS 2基因与其假定的HLA配体的组合更常见（P = 0.030）。此外，我们的研究结果表明，激活KIR 2DS 2-HLA配体对的增加与抑制性KIR-HLA配体对的缺乏相结合，与糖尿病高危HLA等位基因个体发生1型糖尿病的额外风险相关（P = 0.035）。我们认为，KIR和他们的HLA I类配体之间的遗传失衡可能会增强对胰腺自身抗原亲和力低的T细胞的活化，从而促进1型糖尿病的发病机制。
Killer cell immunoglobulin-like receptors (KIRs) modulate natural killer cell and T-cell function by interacting with HLA class 1 ligands on target cells. Both KIR and HLA are highly polymorphic. We studied the influence of KIR and HLA class 1 genes on the susceptibility to develop type 1 diabetes. The results showed increased numbers of activating KIR genes in patients compared with control subjects (P = 0.049). The combination of the activating KIR2DS2 gene, together with its putative HLA ligand, was present more frequently in patients than in diabetes high-risk HLA-matched control subjects (P = 0.030). Moreover, our results imply that an increase in activating KIR2DS2-HLA ligand pairs combined with a lack of inhibitory KIR-HLA ligand pairs is associated with an additional risk to develop type 1 diabetes in individuals with diabetes high-risk HLA alleles (P = 0.035). We propose that the genetic imbalance between KIR and their HLA class I ligands may enhance the activation of T-cells with a low affinity for pancreatic self-antigens, thereby contributing to the pathogenesis of type 1 diabetes.