Frontiers in Immunology (Sep 2021)
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals
- Erick C. Castelli,
- Erick C. Castelli,
- Mateus V. de Castro,
- Michel S. Naslavsky,
- Michel S. Naslavsky,
- Marilia O. Scliar,
- Nayane S. B. Silva,
- Heloisa S. Andrade,
- Andreia S. Souza,
- Raphaela N. Pereira,
- Camila F. B. Castro,
- Camila F. B. Castro,
- Celso T. Mendes-Junior,
- Diogo Meyer,
- Kelly Nunes,
- Larissa R. B. Matos,
- Monize V. R. Silva,
- Jaqueline Y. T. Wang,
- Joyce Esposito,
- Vivian R. Coria,
- Raul H. Bortolin,
- Mario H. Hirata,
- Jhosiene Y. Magawa,
- Edecio Cunha-Neto,
- Edecio Cunha-Neto,
- Edecio Cunha-Neto,
- Verônica Coelho,
- Verônica Coelho,
- Keity S. Santos,
- Keity S. Santos,
- Keity S. Santos,
- Maria Lucia C. Marin,
- Maria Lucia C. Marin,
- Jorge Kalil,
- Jorge Kalil,
- Jorge Kalil,
- Miguel Mitne-Neto,
- Rui M. B. Maciel,
- Maria Rita Passos-Bueno,
- Maria Rita Passos-Bueno,
- Mayana Zatz,
- Mayana Zatz
Affiliations
- Erick C. Castelli
- Department of Pathology, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Erick C. Castelli
- Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Mateus V. de Castro
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Michel S. Naslavsky
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Michel S. Naslavsky
- Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil
- Marilia O. Scliar
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Nayane S. B. Silva
- Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Heloisa S. Andrade
- Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Andreia S. Souza
- Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Raphaela N. Pereira
- Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Camila F. B. Castro
- Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, Brazil
- Camila F. B. Castro
- Centro Universitário Sudoeste Paulista, Avaré, Brazil
- Celso T. Mendes-Junior
- Departamento de Química, Faculdade de Filosofa, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
- Diogo Meyer
- Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil
- Kelly Nunes
- Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil
- Larissa R. B. Matos
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Monize V. R. Silva
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Jaqueline Y. T. Wang
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Joyce Esposito
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Vivian R. Coria
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Raul H. Bortolin
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Mario H. Hirata
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Jhosiene Y. Magawa
- Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Edecio Cunha-Neto
- Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Edecio Cunha-Neto
- Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil
- Edecio Cunha-Neto
- 0Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil
- Verônica Coelho
- Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil
- Verônica Coelho
- 0Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil
- Keity S. Santos
- Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Keity S. Santos
- Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil
- Keity S. Santos
- 0Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil
- Maria Lucia C. Marin
- Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil
- Maria Lucia C. Marin
- 0Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil
- Jorge Kalil
- Departamento de Clínica Médica, Disciplina de Alergia e Imunologia Clínica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Jorge Kalil
- Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil
- Jorge Kalil
- 0Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil
- Miguel Mitne-Neto
- 1Research and Development, Grupo Fleury, São Paulo, Brazil
- Rui M. B. Maciel
- 1Research and Development, Grupo Fleury, São Paulo, Brazil
- Maria Rita Passos-Bueno
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Maria Rita Passos-Bueno
- Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil
- Mayana Zatz
- Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil
- Mayana Zatz
- Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, Brazil
- DOI
- https://doi.org/10.3389/fimmu.2021.742881
- Journal volume & issue
-
Vol. 12
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*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.
Keywords
