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MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals.
Castelli, Erick C; de Castro, Mateus V; Naslavsky, Michel S; Scliar, Marilia O; Silva, Nayane S B; Andrade, Heloisa S; Souza, Andreia S; Pereira, Raphaela N; Castro, Camila F B; Mendes-Junior, Celso T; Meyer, Diogo; Nunes, Kelly; Matos, Larissa R B; Silva, Monize V R; Wang, Jaqueline Y T; Esposito, Joyce; Coria, Vivian R; Bortolin, Raul H; Hirata, Mario H; Magawa, Jhosiene Y; Cunha-Neto, Edecio; Coelho, Verônica; Santos, Keity S; Marin, Maria Lucia C; Kalil, Jorge; Mitne-Neto, Miguel; Maciel, Rui M B; Passos-Bueno, Maria Rita; Zatz, Mayana.
  • Castelli EC; Department of Pathology, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.
  • de Castro MV; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.
  • Naslavsky MS; Human Genome and Stem Cell Research Center, 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; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
  • Andrade HS; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, 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.
  • Mendes-Junior CT; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.
  • Meyer D; Molecular Genetics and Bioinformatics Laboratory-Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil.
  • Nunes K; Centro Universitário Sudoeste Paulista, Avaré, Brazil.
  • Matos LRB; Departamento de Química, Faculdade de Filosofa, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Silva MVR; Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
  • Wang JYT; Department of Genetics and Evolutionary Biology, Biosciences Institute, 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; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.
  • Hirata MH; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.
  • Magawa JY; Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil.
  • Cunha-Neto E; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
  • Coelho V; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, 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.
  • Marin MLC; Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
  • Kalil J; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.
  • Mitne-Neto M; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil.
  • Maciel RMB; Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.
  • Passos-Bueno MR; Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil.
  • Zatz M; Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Front Immunol ; 12: 742881, 2021.
Article in English | MEDLINE | ID: covidwho-1470759
ABSTRACT
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*0301 and DRB1*0401) and DOB*0102 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Asymptomatic Infections / SARS-CoV-2 / COVID-19 / Histocompatibility Antigens / Major Histocompatibility Complex Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: South America / Brazil Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.742881

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Asymptomatic Infections / SARS-CoV-2 / COVID-19 / Histocompatibility Antigens / Major Histocompatibility Complex Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: South America / Brazil Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.742881