Department of Immunology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville, Spain.
Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain.
Front Immunol. 2019 Nov 29;10:2755. doi: 10.3389/fimmu.2019.02755. eCollection 2019.
Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the disease, although the bases of this association remain elusive. NK cells have also been implicated in the etiopathogenesis of BD. A family of NK receptors, Killer-cell Immunoglobulin-like Receptor (KIR), with a very complex organization, is very important in the education and control of the NK cells by the union to their ligands, most of them, HLA class I molecules. This study aimed to investigate the contribution of certain KIR functional polymorphisms to the susceptibility to BD. A total of 466 BD patients and 444 healthy individuals were genotyped in HLA class I (A, B, and C). The set of KIR genes and the functional variants of KIR3DL1/DS1 and KIR2DS4 were also determined. Frequency of KIR3DL1004 was lower in patients than in controls (0.15 vs. 0.20, = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1004, which encodes a misfolded protein, is included in a common telomeric haplotype with only one functional KIR gene, KIR3DL2. Both, KIR3DL1 and KIR3DL2 sense pathogen-associated molecular patterns but they have different capacities to eliminate them. The education of the NK cells depending on the HLA, the balance of KIR3DL1/KIR3DL2 licensed NK cells and the different capacities of these receptors to eliminate pathogens could be involved in the etiopathogenesis of BD.
贝赫切特病（BD）是一种免疫介导的血管炎，与先天和适应性免疫反应失衡有关。感染因子或环境因素可能在遗传易感性个体中引发疾病。HLA-B51 是与该疾病相关性更强的遗传因素，尽管其关联的基础仍不清楚。NK 细胞也与 BD 的发病机制有关。NK 细胞的一个家族，杀伤细胞免疫球蛋白样受体（KIR），具有非常复杂的组织，在 NK 细胞的教育和控制中非常重要，通过与它们的配体结合，其中大多数是 HLA Ⅰ类分子。本研究旨在探讨某些 KIR 功能多态性对 BD 易感性的贡献。共对 466 例 BD 患者和 444 例健康个体进行了 HLA Ⅰ类（A、B 和 C）基因分型。还确定了 KIR 基因组和 KIR3DL1/DS1 和 KIR2DS4 的功能变体。与对照组相比，患者中 KIR3DL1004 的频率较低（0.15 对 0.20， = 0.005，Pc = 0.015；OR = 0.70；95%CI 0.54-0.90），无论 B51 阳性还是阴性。KIR3DL1004 编码一种错误折叠的蛋白质，包含在一个只有一个功能 KIR 基因 KIR3DL2 的常见端粒单倍型中。KIR3DL1 和 KIR3DL2 都能感知病原体相关的分子模式，但它们消除它们的能力不同。NK 细胞的教育取决于 HLA，KIR3DL1/KIR3DL2 许可 NK 细胞的平衡以及这些受体消除病原体的不同能力可能与 BD 的发病机制有关。
