HLA-DQA101:03 和 DQB106:01 是 COVID-19 重症肺炎的危险因素。

IF 5.9 4区医学 Q2 CELL BIOLOGY HLA Pub Date : 2024-07-23 DOI:10.1111/tan.15609

Katsushi Tanaka, Akira Meguro, Yu Hara, Lisa Endo, Ami Izawa, Suguru Muraoka, Ayami Kaneko, Kohei Somekawa, Momo Hirata, Yukiko Otsu, Hiromi Matsumoto, Ryo Nagasawa, Sosuke Kubo, Kota Murohashi, Ayako Aoki, Hiroaki Fujii, Keisuke Watanabe, Nobuyuki Horita, Hideaki Kato, Nobuaki Kobayashi, Ichiro Takeuchi, Atsushi Nakajima, Hidetoshi Inoko, Nobuhisa Mizuki, Takeshi Kaneko

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引用次数: 0

摘要

COVID-19 的临床表现范围很广，从轻微症状到严重肺炎都有。HLA 系统在感染性疾病的免疫反应中起着关键作用。我们的研究旨在调查日本人群中 HLA 与 COVID-19 严重程度之间的关系。研究包括 209 名年龄≥20 岁的日本 COVID-19 患者。研究人员采集了患者的唾液样本，并通过全基因组关联分析的 HLA 估算方法确定了患者的 HLA 基因型。然后评估了 HLA 基因型与 COVID-19 严重程度之间的关联。对呼吸衰竭患者（严重组：91 例）和非呼吸衰竭患者（非严重组：118 例）的等位基因频率进行比较，将数据分为三个时间段：欧米克隆流行前、欧米克隆流行期和本研究的总时间段（2021 年 1 月至 2023 年 5 月）。在比较重症组和非重症组时，重症组的 HLA-DQA1*01:03 等位基因频率（35.1% vs. 10.5%，比值比 [OR] = 4.57，校正 p [pc] = 0.041）和 -DQB1*06:01 等位基因频率（32.4% vs. 7.9%，比值比 [OR] = 5.54，校正 p [pc] = 0.030）明显高于前欧米克龙流行期。在奥米克隆疫情期间，重症组中的 HLA-DQB1*06 （32.4% vs. 7.9%，OR = 5.54，pc = 0.030）明显较高。在整个研究期间，HLA-DQA1*01:03（30.2% vs. 14.4%，OR = 2.57，校正 pc = 0.0013）和-DQB1*06:01（44.5% vs. 26.7%，OR = 2.20，pc = 0.013）等位基因在重症组中明显较高。在整个研究期间，HLA-DQB1*06:01 和 -DQA1*01:03处于强连锁不平衡状态（r2 = 0.91），表明这两个等位基因形成了一个单倍型。在欧米茄流行前（32.4% vs. 7.9%，OR = 5.59，pc = 0.00072）和整个研究期间（28.6% vs. 13.1%，OR = 2.63，pc = 0.0013），重症组的 HLA-DQA1*01:03-DQB1*06:01 频率明显高于非重症组。在 Omicron 流行期间，单倍型没有显示出统计学意义，尽管几率比大于 1。在重症 COVID-19 患者中，HLA-DQA1*01:03 和 -DQB1*06:01 等位基因的频率明显较高，这表明这些等位基因是日本人群中重症 COVID-19 肺炎的风险因素。

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HLA-DQA1*01:03 and DQB1*06:01 are risk factors for severe COVID-19 pneumonia

The clinical spectrum of COVID-19 includes a wide range of manifestations, from mild symptoms to severe pneumonia. HLA system plays a pivotal role in immune responses to infectious diseases. The purpose of our study was to investigate the association between HLA and COVID-19 severity in a Japanese population. The study included 209 Japanese COVID-19 patients aged ≥20 years. Saliva samples were collected and used to determine the HLA genotype by HLA imputation through genome-wide association analyses. The association between HLA genotype and COVID-19 severity was then evaluated. The allele frequency was compared between patients with respiratory failure (severe group: 91 cases) and those without respiratory failure (non-severe group: 118 cases), categorising the data into three time periods: pre-Omicron epidemic period, Omicron epidemic period, and total period of this study (from January 2021 to May 2023). In comparing the severe and non-severe groups, the frequencies of the HLA-DQA1*01:03 (35.1% vs. 10.5%, odds ratio [OR] = 4.57, corrected p [p_c] = 0.041) and -DQB1*06:01 (32.4% vs. 7.9%, OR = 5.54, p_c = 0.030) alleles were significantly higher in the severe group during the pre-Omicron epidemic period. During the Omicron epidemic period, HLA-DQB1*06 (32.4% vs. 7.9%, OR = 5.54, p_c = 0.030) was significantly higher in the severe group. During total period of this study, HLA-DQA1*01:03 (30.2% vs. 14.4%, OR = 2.57, corrected p_c = 0.0013) and -DQB1*06:01 (44.5% vs. 26.7%, OR = 2.20, p_c = 0.013) alleles were significantly higher in the severe group. HLA-DQB1*06:01 and -DQA1*01:03 were in strong linkage disequilibrium with each other (r² = 0.91) during total period of this study, indicating that these two alleles form a haplotype. The frequency of the HLA-DQA1*01:03–DQB1*06:01 in the severe group was significantly higher than in the non-severe group during pre-Omicron epidemic period (32.4% vs. 7.9%, OR = 5.59, p_c = 0.00072), and total period of this study (28.6% vs. 13.1%, OR = 2.63, p_c = 0.0013). During Omicron epidemic period, the haplotype did not demonstrate statistical significance, although the odds ratio indicated a value greater 1. Frequencies of the HLA-DQA1*01:03 and -DQB1*06:01 alleles were significantly higher in severe COVID-19 patients, suggesting that these alleles are risk factors for severe COVID-19 pneumonia in the Japanese population.

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来源期刊

HLA Immunology and Microbiology-Immunology

CiteScore

3.00

自引率

28.80%

发文量

368

期刊介绍： HLA, the journal, publishes articles on various aspects of immunogenetics. These include the immunogenetics of cell surface antigens, the ontogeny and phylogeny of the immune system, the immunogenetics of cell interactions, the functional aspects of cell surface molecules and their natural ligands, and the role of tissue antigens in immune reactions. Additionally, the journal covers experimental and clinical transplantation, the relationships between normal tissue antigens and tumor-associated antigens, the genetic control of immune response and disease susceptibility, and the biochemistry and molecular biology of alloantigens and leukocyte differentiation. Manuscripts on molecules expressed on lymphoid cells, myeloid cells, platelets, and non-lineage-restricted antigens are welcomed. Lastly, the journal focuses on the immunogenetics of histocompatibility antigens in both humans and experimental animals, including their tissue distribution, regulation, and expression in normal and malignant cells, as well as the use of antigens as markers for disease.