Erer B, Takeuchi M, Ustek D, Tugal-Tutkun I, Seyahi E, Özyazgan Y, Duymaz-Tozkir J, Gül A, Kastner D L, Remmers E F, Ombrello M J
Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA.
Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Genes Immun. 2016 Dec;17(7):396-399. doi: 10.1038/gene.2016.36. Epub 2016 Oct 6.
The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B51 (B51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, P=0.55; KIR3DS1: 42.7% vs 41.0%, P=0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B51. Our results suggest that pathogenic mechanisms associated with HLA-B51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.
与白塞病（BD）相关的人类白细胞抗原（HLA）等位基因HLA - B51（B51）编码一种配体，该配体可与细胞毒性细胞上存在的一对等位基因杀伤免疫球蛋白样受体（KIR）结合——KIR3DL1可抑制其细胞毒性，而KIR3DS1可激活其细胞毒性活性。我们通过检测1799名来自土耳其的BD患者和1710名健康对照中KIR3DL1/KIR3DS1基因型与疾病的关联性，以及在具有KIR3D受体HLA型定义配体的不同个体亚组中进行检测，来检验KIR调节机制是否对白塞病有影响。HLA类型是根据用免疫芯片测定的单核苷酸多态性基因型推算出来的。抑制性KIR3DL1或激活性KIR3DS1等位基因在病例组和对照组之间没有显著差异（KIR3DL1：92.9%对93.4%，P = 0.55；KIR3DS1：42.7%对41.0%，P = 0.29）。在携带具有Bw4基序的HLA - B、在第80位具有异亮氨酸的具有Bw4基序的HLA - B以及HLA - B51的病例和对照中，KIR3DL1/KIR3DS1等位基因的出现频率也相似。我们的结果表明，与HLA - B51相关的致病机制并不主要涉及与KIR3DL1和KIR3DS1受体的差异相互作用。然而，由于该基因座的复杂性（即序列变异和拷贝数变异），我们不能排除其他类型的KIR变异在白塞病发病机制中的作用。
