دورية أكاديمية
أعرض في EDS

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

التفاصيل البيبلوغرافية
العنوان: MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.
المؤلفون: Castelli EC; Department of Pathology, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.; Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (Unipex), 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 (Unipex), School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Pereira RN; Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (Unipex), School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Ciriaco VAO; Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (Unipex), School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil., Castro CFB; Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (Unipex), 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., Silveira ES; Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., de Oliveira IM; Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Antonio EC; Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Vieira GF; Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Laboratório de Saúde Humana In Silico, Programa de Pós-Graduação em Saúde e Desenvolvimento Humano, Universidade La Salle, Canoas, 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., Cória VR; Human Genome and Stem Cell Research Center, 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.; 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., 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., 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., 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., Dell'Aquila LP; Prevent Senior Institute, São Paulo, Brazil., Razuk-Filho A; Prevent Senior Institute, São Paulo, Brazil., Batista-Júnior PB; Prevent Senior Institute, São Paulo, Brazil., Duarte-Neto AN; Department of Pathology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil., Dolhnikoff M; Department of Pathology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil., Saldiva PHN; Department of Pathology, School of Medicine, University of Sao Paulo, Sao 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] 2022 Oct 25; Vol. 13, pp. 975918. Date of Electronic Publication: 2022 Oct 25 (Print Publication: 2022).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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: COVID-19*/epidemiology , COVID-19*/genetics, Aged ; Humans ; Brazil/epidemiology ; Genes, MHC Class II ; HLA-A Antigens ; SARS-CoV-2/genetics
مستخلص: Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome.
Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started.
Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24).
Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.
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 © 2022 Castelli, de Castro, Naslavsky, Scliar, Silva, Pereira, Ciriaco, Castro, Mendes-Junior, Silveira, de Oliveira, Antonio, Vieira, Meyer, Nunes, Matos, Silva, Wang, Esposito, Cória, Magawa, Santos, Cunha-Neto, Kalil, Bortolin, Hirata, Dell’Aquila, Razuk-Filho, Batista-Júnior, Duarte-Neto, Dolhnikoff, Saldiva, Passos-Bueno and Zatz.)
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معلومات مُعتمدة: R01 GM075091 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: COVID-19; HLA; MUC22; SARS-CoV-2; human leukocyte antigens; immune response; major histocompatibility complex (MCH); resistant genetic variants
المشرفين على المادة: 0 (HLA-A Antigens)
0 (MUC22 protein, human)
تواريخ الأحداث: Date Created: 20221117 Date Completed: 20221122 Latest Revision: 20221222
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9641602
DOI: 10.3389/fimmu.2022.975918
PMID: 36389712
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-3224
DOI:10.3389/fimmu.2022.975918