Dataset Information

Principal contribution of HLA-DQ alleles, DQB106:04 and DQB103:01, to disease resistance against primary biliary cholangitis in a Japanese population.

ABSTRACT: Identification of the primary allele(s) in HLA class II associated diseases remains challenging because of a tight linkage between alleles of HLA-DR and -DQ loci. In the present study, we determined the genotypes of seven HLA loci (HLA-A, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) for 1200 Japanese patients with primary biliary cholangitis and 1196 controls. Observation of recombination derivatives facilitated an evaluation of the effects of individual HLA alleles consisting of disease-prone/disease-resistant HLA haplotypes. Consequently, a primary contribution of DQB1*06:04 (odds ratio: 0.19, p?=?1.91?×?10-22), DQB1*03:01 (odds ratio: 0.50, p?=?6.76?×?10-10), DRB1*08:03 (odds ratio: 1.75, p?=?1.01?×?10-7) and DQB1*04:01 (odds ratio: 1.50, p?=?9.20?×?10-6) was suggested. Epistasis of the protective DQB1*06:04 to risk conferred by DRB1*08:03 was demonstrated by subpopulation analysis, implicating the presence of an active immunological mechanism that alleviates pathogenic autoimmune reactions. Further, the contribution of the aforementioned HLA alleles as well as an HLA-DP allele, DPB1*02:01 to the association signals of 304 loci among 4103 SNPs in the HLA region at the genome-wide level of significance (p values less than 5?×?10-8) was demonstrated by the stepwise exclusion of the individuals possessing these HLA alleles from the comparison.

SUBMITTER: Yasunami M

PROVIDER: S-EPMC5593890 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Principal contribution of HLA-DQ alleles, DQB106:04 and DQB103:01, to disease resistance against primary biliary cholangitis in a Japanese population.

Yasunami Michio M Nakamura Hitomi H Tokunaga Katsushi K Kawashima Minae M Nishida Nao N Hitomi Yuki Y Nakamura Minoru M

Scientific reports 20170911 1

Identification of the primary allele(s) in HLA class II associated diseases remains challenging because of a tight linkage between alleles of HLA-DR and -DQ loci. In the present study, we determined the genotypes of seven HLA loci (HLA-A, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) for 1200 Japanese patients with primary biliary cholangitis and 1196 controls. Observation of recombination derivatives facilitated an evaluation of the effects of individual HLA alleles consisting of disease-prone/dise ...[more]

PMID: 28894202

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Project description:BackgroundHLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8+ T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have different levels of expression and affinity for MHC Ia-derived peptide raises the question of whether HLA-E polymorphisms affect susceptibility to COVID-19 or its severity.Methods104 COVID-19 convalescent plasma donors with/without history of hospitalization and 18 blood donors with asymptomatic COVID-19, all were positive for anti-SARS-CoV-2 IgG antibody as well as a group of healthy control including 68 blood donors with negative antibody were subjected to HLA-E genotyping. As a privilege, individuals hadn't been vaccinated against COVID-19 and therefore naturally exposed to the SARS-CoV-2.ResultsThe absence of HLA-E*01:03 allele significantly decreases the odds of susceptibility to SARS-CoV-2 infection [p = 0.044; OR (95 %CI) = 0.530 (0.286 - 0.983)], suggesting that HLA-E*01:01 + HLA-E*01:01 genotype favors more protection against SARS-CoV-2 infection. HLA-E*01:03 + HLA-E*01:03 genotype was also significantly associated with more severe COVID-19 [p = 0.020; 2.606 (1.163 - 5.844) CONCLUSION: Here, our observation about lower susceptibility of HLA-E*01:01 + HLA-E*01:01 genotype to COVID-19 could be clinical evidence in support of some previous studies suggesting that the lower affinity of HLA-E*01:01 to peptides derived from the leader sequence of MHC class Ia may instead shift its binding to virus-derived peptides, which then facilitates target recognition by restricted conventional CD8+ T cells and leads to efficient cytolysis. On the other hand, according to other studies, less reactivity of HLA-E*01:01 with NKG2A abrogates NK cells or T cells inhibition, which may also lead to a greater cytotoxicity against SARS-CoV-2 infected cells compared to HLA-E*01:03. Taken together given HLA-E polymorphisms, the data presented here may be useful in identifying more vulnerable individuals to COVID-19 for better care and management. Especially since along with other risk factors in patients, having HLA-E*01:03 + HLA-E*01:03 genotype may also be associated with the possibility of severe cases of the disease.

Dataset Information

Principal contribution of HLA-DQ alleles, DQB106:04 and DQB103:01, to disease resistance against primary biliary cholangitis in a Japanese population.

Publications

Principal contribution of HLA-DQ alleles, DQB106:04 and DQB103:01, to disease resistance against primary biliary cholangitis in a Japanese population.

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Dataset Information

Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population.

Publications

Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Principal contribution of HLA-DQ alleles, DQB106:04 and DQB103:01, to disease resistance against primary biliary cholangitis in a Japanese population.

Principal contribution of HLA-DQ alleles, DQB106:04 and DQB103:01, to disease resistance against primary biliary cholangitis in a Japanese population.