دورية أكاديمية
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals.
| العنوان: | MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals. |
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| المؤلفون: | Castelli EC; Department of Pathology, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., de Castro MV; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Naslavsky MS; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil., Scliar MO; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Silva NSB; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Andrade HS; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Souza AS; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Pereira RN; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Castro CFB; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.; Centro Universitário Sudoeste Paulista, Avaré, Brazil., Mendes-Junior CT; Departamento de Química, Faculdade de Filosofa, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil., Meyer D; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil., Nunes K; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil., Matos LRB; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Silva MVR; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Wang JYT; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Esposito J; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Coria VR; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil., Bortolin RH; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Hirata MH; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Magawa JY; Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Cunha-Neto E; Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil., Coelho V; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil., Santos KS; Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil., Marin MLC; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil., Kalil J; Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil., Mitne-Neto M; Research and Development, Grupo Fleury, São Paulo, Brazil., Maciel RMB; Research and Development, Grupo Fleury, São Paulo, Brazil., Passos-Bueno MR; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil., Zatz M; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 Sep 28; Vol. 12, pp. 742881. Date of Electronic Publication: 2021 Sep 28 (Print Publication: 2021). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Asymptomatic Infections* , COVID-19*/genetics , COVID-19*/immunology , Histocompatibility Antigens*/genetics , Histocompatibility Antigens*/immunology , Major Histocompatibility Complex*/genetics , Major Histocompatibility Complex*/immunology , SARS-CoV-2*, Adult ; Aged ; Brazil ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Exome Sequencing |
| مستخلص: | Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as "discordant couples". We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Castelli, de Castro, Naslavsky, Scliar, Silva, Andrade, Souza, Pereira, Castro, Mendes-Junior, Meyer, Nunes, Matos, Silva, Wang, Esposito, Coria, Bortolin, Hirata, Magawa, Cunha-Neto, Coelho, Santos, Marin, Kalil, Mitne-Neto, Maciel, Passos-Bueno and Zatz.) |
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| فهرسة مساهمة: | Keywords: COVID-19; HLA; MHC; MICA; MICB; SARS-CoV-2; asymptomatic; resistance |
| المشرفين على المادة: | 0 (Histocompatibility Antigens) |
| تواريخ الأحداث: | Date Created: 20211015 Date Completed: 20211025 Latest Revision: 20240817 |
| رمز التحديث: | 20240817 |
| مُعرف محوري في PubMed: | PMC8506217 |
| DOI: | 10.3389/fimmu.2021.742881 |
| PMID: | 34650566 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.742881 |