HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.
HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.
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SARS-CoV-2感染会导致不同的结果，从无症状的感染到轻微或严重的疾病和死亡。结果差异的原因包括挑战剂量、年龄、性别、合并症和宿主基因组变异的差异。人类白细胞抗原(人类白细胞抗原)基因多态性可能影响免疫反应和疾病转归。我们调查了HLAII等位基因与病例定义、症状性新冠肺炎、病毒特异性抗体和T细胞免疫的相关性。在英国SARS-CoV-2第一波期间，总共招募了1,364名英国医护人员(HCW)，并进行了纵向分析，包括定期的聚合酶链式反应(PCR)感染筛查、症状报告、HLAII基因归属以及抗体和T细胞对核蛋白(N)和尖峰蛋白(Spike)的反应分析(S)。在272例(20%)血清转换的HCW中，HLADRB1*13：02与病例定义为症状性新冠肺炎的危险性增加6.7倍相关，在免疫应答方面，HLADRB1*15：02与较低的核衣壳T细胞应答相关。在两次接种COVID疫苗后，DRB1等位基因与抗尖峰抗体滴度之间没有关联。然而，HLADRB1*15：01与第一次和第二次疫苗接种后尖峰T细胞反应增加相关。试验注册：NCT04318314和ISRCTN15677965。SARS-CoV-2感染会导致不同的结果，从无症状感染到轻微或严重的疾病和死亡。我们调查了HLAII等位基因与病例定义、症状性新冠肺炎、病毒特异性抗体和T细胞免疫的相关性。HLADRB1*13：02的存在与出现症状性新冠肺炎的风险增加相关，而在接种疫苗后，HLADRB1*15：01与尖峰T细胞应答增加相关。
SARS‐CoV‐2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID‐19, virus‐specific antibody and T‐cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS‐CoV‐2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T‐cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA‐DRB1*13:02 was associated with a 6·7‐fold increased risk of case definition symptomatic COVID‐19. In terms of immune responsiveness, HLA‐DRB1*15:02 was associated with lower nucleocapsid T‐cell responses. There was no association between DRB1 alleles and anti‐spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T‐cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965. SARS‐CoV‐2 infection results in different outcomes ranging from asymptomatic infection, to mild or severe disease and death. We investigated the association of HLAII alleles with case definition symptomatic COVID‐19, virus‐specific antibody and T cell immunity. Presence of HLA‐DRB1*13:02 was associated with increased risk of symptomatic COVID‐19, while, after vaccination, HLA DRB1*15:01 was associated with increased spike T cell responses.
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DOI：
10.1073/pnas.88.16.7343
发表时间：
1991-08-01
影响因子：
11.1
作者：
ONG, B;WILLCOX, N;NEWSOMDAVIS, J
通讯作者：
NEWSOMDAVIS, J
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
Casanova JL
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
3.1
作者：
Ovsyannikova, Inna G.;Pankratz, V. Shane;Poland, Gregory A.
通讯作者：
Poland, Gregory A.
DOI：
10.1073/pnas.92.14.6567
发表时间：
1995-07-03
影响因子：
11.1
作者：
DAVENPORT, MP;QUINN, CL;HILL, AVS
通讯作者：
HILL, AVS