Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.
Hepatic Disease Institute, Hubei Key Laboratory of Theoretical and Applied Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.
Front Immunol. 2022 Jul 7;13:919110. doi: 10.3389/fimmu.2022.919110. eCollection 2022.
SARS-CoV-2 is the causative agent for the global COVID-19 pandemic; however, the interaction between virus and host is not well characterized. Natural killer cells play a key role in the early phase of the antiviral response, and their primary functions are dependent on signaling through the killer cell immunoglobulin-like receptor (KIR). This study measured the association between KIR/HLA class I ligand pairings and the occurrence and development of COVID-19. DNA of blood samples from 257 COVID-19 patients were extracted and used to detect KIR and HLA-C gene frequencies using single strain sequence-specific primer (SSP) PCR. The frequency of these genes was compared among 158 individuals with mild COVID-19, 99 with severe disease, and 98 healthy controls. The frequencies of KIR2DL2 (P=0.04, OR=1.707), KIR2DS3 (P=0.047, OR=1.679), HLA-C1C1 (P<0.001, OR=3.074) and the KIR2DL2/HLA-C1C1 pairing (P=0.038, OR=2.126) were significantly higher in the COVID-19 patients than the healthy controls. At the same time, the frequency of KIR2DL3+KIR2DL2-/HLA-C1+Others+ was lower in COVID-19 patients than in healthy individuals (P=0.004, OR=0.477). These results suggest that the protective effect of KIR2DL3 against SARS-CoV-2 infection is related to the absence of the KIR2DL2 gene. This study found no correlation between the frequencies of these genes and COVID-19 pathogenesis. Global statistical analysis revealed that the incidence of COVID-19 infection was higher in geographic regions with a high frequency of KIR2DL2. Together these results suggest that the KIR2DL2/HLA-C1C1 gene pairing may be a risk factor for SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒 2 是导致全球 COVID-19 大流行的病原体；然而，病毒与宿主之间的相互作用尚未得到充分描述。自然杀伤细胞在抗病毒反应的早期阶段发挥关键作用，其主要功能依赖于通过杀伤细胞免疫球蛋白样受体（KIR）进行信号传递。本研究测量了 KIR/HLA I 类配体对 COVID-19 的发生和发展的关联。从 257 例 COVID-19 患者的血液样本中提取 DNA，使用单株序列特异性引物（SSP）PCR 检测 KIR 和 HLA-C 基因频率。将这些基因的频率在 158 例轻度 COVID-19 患者、99 例重症患者和 98 例健康对照者中进行比较。KIR2DL2（P=0.04，OR=1.707）、KIR2DS3（P=0.047，OR=1.679）、HLA-C1C1（P<0.001，OR=3.074）和 KIR2DL2/HLA-C1C1 配对（P=0.038，OR=2.126）的频率在 COVID-19 患者中明显高于健康对照组。与此同时，COVID-19 患者中 KIR2DL3+KIR2DL2-/HLA-C1+Others+的频率低于健康个体（P=0.004，OR=0.477）。这些结果表明，KIR2DL3 对 SARS-CoV-2 感染的保护作用与缺乏 KIR2DL2 基因有关。本研究未发现这些基因的频率与 COVID-19 发病机制之间存在相关性。全球统计分析显示，在 KIR2DL2 频率较高的地理区域，COVID-19 感染的发病率较高。这些结果表明，KIR2DL2/HLA-C1C1 基因配对可能是 SARS-CoV-2 感染的危险因素。
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