HLA Typing Laboratory, Blood Center of the Shaanxi Province, Institute of Xi'an Blood Bank, Xi'an, Shaanxi, 710061, China.
Immunogenetics. 2023 Oct;75(5):445-454. doi: 10.1007/s00251-023-01316-6. Epub 2023 Aug 17.
Regulating natural killer (NK) cell responses in hematological malignancies largely depend on molecular interactions between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I ligands. The goal of the current study was to examine the key functions of KIR genes, gene combinations of KIR-HLA, and KIR genotypes in genetic predisposition to aplastic anemia (AA). Herein, the genotyping of 16 KIR genes and HLA-A, -B, and -C ligands were performed in 72 AA patients and 150 healthy controls using PCR evaluations with sequence-specific primers using standard assays. According to the obtained results, AA patients had an increased incidence of activating KIR and KIR2DS4 (P = 0.465 × 10, Pc = 0.837 × 10, OR = 20.81, 95% CI = 2.786-155.5) compared to controls. KIR/HLA class I ligand profile KIR2DS4/C1 (P = 0.350 × 10, Pc = 0.630 × 10, OR = 8.944, 95% CI = 2.667-29.993) was significantly elevated in AA patients compared to healthy controls. Genotype AA1 (P = 0.003, OR = 2.351, 95% CI = 1.325-4.172) were increased, and AA195 (P = 0.006, OR = 0.060, 95% CI = 0.004-1.023) was decreased among AA cases compared to controls. Our findings indicated that KIR2DS4 may play a role in the pathogenesis of AA. This study revealed the contribution of KIR genes in the etiology of AA cases.
自然杀伤 (NK) 细胞反应在血液恶性肿瘤中的调节在很大程度上取决于杀伤细胞免疫球蛋白样受体 (KIR) 和人类白细胞抗原 (HLA) Ⅰ类配体之间的分子相互作用。本研究旨在研究 KIR 基因、KIR-HLA 基因组合和 KIR 基因型在再生障碍性贫血 (AA) 遗传易感性中的关键作用。在此,使用聚合酶链反应 (PCR) 评估技术和序列特异性引物,对 72 例 AA 患者和 150 例健康对照者的 16 个 KIR 基因和 HLA-A、-B 和 -C 配体进行基因分型,采用标准方法进行检测。根据研究结果,与对照组相比,AA 患者活化性 KIR 和 KIR2DS4 的发生率增加(P=0.465×10,Pc=0.837×10,OR=20.81,95%CI=2.786-155.5)。与健康对照组相比,AA 患者的 KIR/HLA Ⅰ类配体谱 KIR2DS4/C1 明显升高(P=0.350×10,Pc=0.630×10,OR=8.944,95%CI=2.667-29.993)。与对照组相比,AA 患者的 AA1 基因型(P=0.003,OR=2.351,95%CI=1.325-4.172)增加,AA195 基因型(P=0.006,OR=0.060,95%CI=0.004-1.023)减少。这些发现表明 KIR2DS4 可能在 AA 的发病机制中发挥作用。本研究揭示了 KIR 基因在 AA 病例发病机制中的作用。