Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience.
Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience.
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人白细胞抗原复合物以及其他免疫遗传和临床因素会影响对SARS-COV-2感染和疾病病程严重程度的敏感性或保护。撒丁岛的经历。
DOI：
10.3389/fimmu.2020.605688
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发表时间：
2020
影响因子：
7.3
通讯作者：
Chessa L
中科院分区：
文献类型：
--
作者：
Littera R;Campagna M;Deidda S;Angioni G;Cipri S;Melis M;Firinu D;Santus S;Lai A;Porcella R;Lai S;Rassu S;Scioscia R;Meloni F;Schirru D;Cordeddu W;Kowalik MA;Serra M;Ragatzu P;Carta MG;Del Giacco S;Restivo A;Deidda S;Orrù S;Palimodde A;Perra R;Orrù G;Conti M;Balestrieri C;Serra G;Onali S;Marongiu F;Perra A;Chessa L
SARS-CoV-2感染是一个全球性的公共卫生问题。其发病机制和相关的临床后果的几个方面仍然需要阐明。在意大利，撒丁岛的感染人数非常低。利用撒丁岛人群的低遗传多态性，我们分析了临床，遗传和免疫遗传因素，特别是HLA I类和II类分子，以评估其对SARS-CoV-2感染的易感性和临床结果的影响。我们招募了619名健康的撒丁岛对照和182名SARS-CoV-2患者。39名患者需要住院治疗，143名患者没有症状，症状很少或病情轻微。对于所有参与者，我们收集了人口统计学和临床数据，并分析了HLA等位基因和单倍型频率。男性和老年人在住院患者中更常见，他们中没有人在以前的季节性流感疫苗接种期间接种过疫苗。与无症状或症状少的患者组相比，住院患者也有更高的自身免疫性疾病和葡萄糖-6-磷酸脱氢酶（G6 PDH）缺乏症的频率。这些患者都没有携带β地中海贫血性状，这是撒丁岛人口中相对常见的发现。所有182例患者中均不存在扩展单倍型HLA-A*02：05，B*58：01，C*07：01，DRB 1 *03：01 [OR 0.1（95%CI 0-0.6），Pc = 0.015]，而HLA-C*04：01等位基因和三位点单倍型HLA-A*30：02，B*14：02，C*08：02 [OR 3.8（95%CI 1.8-8.1），Pc = 0.025]在患者中的出现频率高于对照组。在住院患者和家庭护理患者之间的比较中，HLA-DRB 1 *08：01等位基因仅存在于住院患者中[OR > 2.5（95%CI 2.7-220.6），Pc = 0.024]。从我们的研究中出现的数据表明，扩展的单倍型HLA-A*02：05，B*58：01，C*07：01，DRB 1 *03：01在撒丁岛人群中对SARS-CoV-2感染具有保护作用。导致对疾病过程产生负面影响的遗传因素是HLA-DRB 1 *08：01等位基因和G6 PDH缺乏症的存在，但不是β-地中海贫血性状。缺乏流感疫苗接种可能是更严重疾病的诱发因素。
SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome. We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies. Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024]. The data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.
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