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在马德里居住的厄瓜多尔患者的 HLA/KIR 多态性与 2019 冠状病毒病风险和保护因素的相关性研究。

Coronavirus-19 disease risk and protective factors associated with HLA/KIR polymorphisms in Ecuadorian patients residing in Madrid.

机构信息

Histocompatibility Unit, Centro de Transfusion de la Comunidad de Madrid, Madrid, Spain.

National Referral Unit for Imported Tropical Diseases and Travel Medicine, Infectious Diseases Department, Hospital Universitario La Paz-Carlos III, IdiPAZ, CIBERINFEC, Madrid, Spain.

出版信息

Hum Immunol. 2023 Nov;84(11):571-577. doi: 10.1016/j.humimm.2023.09.004. Epub 2023 Sep 28.

Abstract

BACKGROUND

Immigrants represented 21.8% of cases in a Spanish cohort of hospitalised patients with COVID-19, a proportion exceeding the percentage of immigrants in that area's total population. Among the ethnic-related genetic risk factors for COVID-19, human leukocyte antigen (HLA) genotypes in diverse populations might bias the response to SARS-CoV-2 infection and/or progression. Similarly, genetic differences in natural killer-activating and inhibitory receptors could play a role in the immune system's response to the viral infection.

METHODS

We characterised HLA alleles and KIR genes in 52 Ecuadorian patients hospitalised for moderate and severe COVID-19 and 87 Ecuadorian controls from the general population living in the same area.

RESULTS

There was a significantly increased frequency of the HLA-B39 antigen and the activating KIR2DS4 receptor in the presence of its HLA-C04 ligand in the COVID-19 group when compared with the control group. In contrast, there was a significant reduction in the frequency of carriers of KIR2DL1 and of the KIR3DL1/Bw4 receptor/ligand combination among COVID-19 group. On the other hand, HLA-A24:02 and HLA-DRB109:01 alleles showed significantly lower frequencies specifically in the severe COVID-19 group.

CONCLUSION

HLA-B39 alleles might be genetic risk factors for developing COVID-19 in Ecuadorian individuals. In the presence of its ligand C04, the natural killer-activating receptor KIR2DS4 might also increase the risk of developing COVID-19, while, in the presence of HLA-Bw4 alleles, the inhibitory receptor KIR3DL1 might play a protective role. Patients with COVID-19 who carry HLA-A24:02 and HLA-DRB109:01 alleles might be protected against more severe forms of COVID-19.

摘要

背景

在西班牙因 COVID-19 住院的患者队列中,移民占 21.8%,这一比例超过了该地区移民在总人口中所占的比例。在与 COVID-19 相关的与种族有关的遗传风险因素中,人类白细胞抗原(HLA)在不同人群中的基因型可能会影响对 SARS-CoV-2 感染和/或进展的反应。同样,自然杀伤细胞激活和抑制受体的遗传差异可能在免疫系统对病毒感染的反应中发挥作用。

方法

我们在 52 名因 COVID-19 住院的厄瓜多尔患者和 87 名来自同一地区的普通人群中的厄瓜多尔对照中,对 HLA 等位基因和 KIR 基因进行了特征描述。

结果

与对照组相比,COVID-19 组中 HLA-B39 抗原和激活型 KIR2DS4 受体与其 HLA-C04 配体同时存在的频率显著增加。相比之下,COVID-19 组中 KIR2DL1 和 KIR3DL1/Bw4 受体/配体组合的携带者频率显著降低。另一方面,HLA-A24:02 和 HLA-DRB109:01 等位基因在重症 COVID-19 组中的频率明显较低。

结论

HLA-B39 等位基因可能是厄瓜多尔个体患 COVID-19 的遗传风险因素。在其配体 C04 存在的情况下,自然杀伤细胞激活受体 KIR2DS4 也可能增加患 COVID-19 的风险,而在 HLA-Bw4 等位基因存在的情况下,抑制性受体 KIR3DL1 可能发挥保护作用。携带 HLA-A24:02 和 HLA-DRB109:01 等位基因的 COVID-19 患者可能免受更严重形式的 COVID-19 的影响。

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