Division of Transplant Immunology and Immunogenetics, Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran.
Int J Immunogenet. 2011 Oct;38(5):403-9. doi: 10.1111/j.1744-313X.2011.01024.x. Epub 2011 Jul 29.
Contribution of killer cell immunoglobulin-like receptors (KIR) and their human leucocyte antigen (HLA) class I ligands in the pathogenesis of autoimmune diseases has been shown in several studies. In this study, the possible association of KIR genes, their known HLA ligands and compound KIR/HLA genotypes with ankylosing spondylitis (AS) was assessed. Combined KIR/HLA ligand genotyping was performed by a polymerase chain reaction-sequence-specific primers assay in 35 Iranian patients with AS, and genotypes were compared to those in 200 healthy individuals. The frequencies of telomeric cluster genes KIR2DL5A, KIR2DS1 and KIR3DS1 were significantly increased in AS patient group (P(c) = 0.0082, P(c) = 0.0195 and P(c) = 0.0328, respectively). Conversely, HLA-Bw4 ligand (the presence of one or more -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4 epitopes) (P(c) = 0.0004) and HLA-B Bw4(Ile80) (P(c) = 0.053) were less frequent in these patients. Meanwhile, compound KIR/HLA genotype analyses revealed lower frequency of KIR3DL1+HLA-B Bw4(Ile80) (P(c) = 0.0343) and higher frequency of KIR2DS1+HLA-C2 (P(c) = 0.0308) combinations in patients with AS than in controls. In addition, the genotypes iKIR+HLA > aKIR+HLA (P(c) = .0308) and iKIR+HLA > aKIR (P(c) = 0.0258) were statistically less common, and genotypes iKIR+HLA = aKIR+HLA (P(c) = 0.0081) and iKIR+HLA < aKIR (P(c) = 0.077) were more common in patient group. Our findings suggest a role for excessive or inappropriate NK cell activation through 'KIR/HLA' system in AS disease.
已有多项研究表明，杀伤细胞免疫球蛋白样受体（KIR）及其人类白细胞抗原（HLA）I 类配体在自身免疫性疾病的发病机制中发挥作用。本研究评估了 KIR 基因及其已知的 HLA 配体和复合 KIR/HLA 基因型与强直性脊柱炎（AS）的可能相关性。采用聚合酶链反应-序列特异性引物法对 35 例伊朗 AS 患者进行联合 KIR/HLA 配体基因分型，并与 200 例健康对照者的基因型进行比较。AS 患者组 KIR2DL5A、KIR2DS1 和 KIR3DS1 端粒簇基因的频率显著增加（P(c)=0.0082、P(c)=0.0195 和 P(c)=0.0328）。相反，这些患者 HLA-Bw4 配体（存在一个或多个-B Bw4(Ile80)、-B Bw4(Thr80)和-A Bw4 表位）（P(c)=0.0004）和 HLA-B Bw4(Ile80)（P(c)=0.053）的频率较低。同时，复合 KIR/HLA 基因型分析显示，AS 患者中 KIR3DL1+HLA-B Bw4(Ile80)（P(c)=0.0343）的频率较低，KIR2DS1+HLA-C2（P(c)=0.0308）的频率较高。此外，iKIR+HLA > aKIR+HLA（P(c)=0.0308）和 iKIR+HLA > aKIR（P(c)=0.0258）的基因型较少，而 iKIR+HLA = aKIR+HLA（P(c)=0.0081）和 iKIR+HLA < aKIR（P(c)=0.077）的基因型更为常见。我们的研究结果表明，通过“KIR/HLA”系统，NK 细胞过度或不适当的激活在 AS 疾病中起作用。
