Mohammad-Ebrahim H, Kamali-Sarvestani E, Mahmoudi M, Beigy M, Karami J, Ahmadzadeh N, Shahram F
a Department of Immunology, School of Medicine , Shiraz University of Medical Sciences , Shiraz , Iran.
b Autoimmune Disease Research Centre , Shiraz University of Medical Sciences , Shiraz , Iran.
Scand J Rheumatol. 2018 Mar;47(2):155-163. doi: 10.1080/03009742.2017.1340510. Epub 2017 Sep 1.
Behçet's disease (BD) is a systemic inflammatory disorder with remissions and exacerbations. It is thought that defects in the natural killer (NK) cell repertoire may be involved in BD through killer cell immunoglobulin-like receptors (KIRs). This study aimed to evaluate KIR and HLA genes, their interactions in BD patients, and their associations with clinical manifestations.
The presence or absence of KIR and HLA alleles and genotypes was analysed by polymerase chain reaction sequence-specific primer on genomic DNA of 397 BD patients and 300 healthy controls.
None of the KIR genes showed significant effects on BD susceptibility. HLA-C1 showed a protective effect against BD, whereas HLA-C2, HLA-B-Bw4, HLA-B5, and HLA-B51 were associated with a susceptibility risk for BD. In the combination of KIR and HLA genes, the frequencies of HLA genotypes no. 2, 3, 5, and 8, and inhibitory KIR no. 4 were significantly higher in patients than in controls. The frequencies of KIR genotype no. 3 and HLA genotypes no. 1, 4, 6, 7, and 9 were significantly lower in patients than in controls. There were many associations between KIR and HLA genes with clinical features of BD.
Differences in the frequency of HLA genes, KIR-HLA interactions, and genotypes between BD and healthy controls and their associations with clinical manifestations indicate that NK cells are involved in BD pathogenesis. The observed differences indicated an NK cell activity imbalance in BD patients, and suggest a role of the KIR-HLA repertoire in the development of BD.
白塞病（BD）是一种具有缓解期和加重期的全身性炎症性疾病。人们认为自然杀伤（NK）细胞库的缺陷可能通过杀伤细胞免疫球蛋白样受体（KIR）参与BD的发病过程。本研究旨在评估KIR和HLA基因、它们在BD患者中的相互作用以及它们与临床表现的关联。
采用聚合酶链反应序列特异性引物，对397例BD患者和300例健康对照者的基因组DNA进行KIR和HLA等位基因及基因型的检测。
没有KIR基因对BD易感性显示出显著影响。HLA-C1对BD有保护作用，而HLA-C2、HLA-B-Bw4、HLA-B5和HLA-B51与BD的易感性风险相关。在KIR和HLA基因的组合中，患者中HLA基因型2、3、5和8以及抑制性KIR 4的频率显著高于对照组。患者中KIR基因型3以及HLA基因型1、4、6、7和9的频率显著低于对照组。KIR和HLA基因与BD的临床特征之间存在许多关联。
BD患者与健康对照者在HLA基因频率、KIR-HLA相互作用及基因型方面的差异，以及它们与临床表现的关联表明NK细胞参与了BD的发病机制。观察到的差异表明BD患者存在NK细胞活性失衡，并提示KIR-HLA库在BD发生发展中起作用。
