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https://www.arca.fiocruz.br/handle/icict/20569
THE PRESENCE, PERSISTENCE AND FUNCTIONAL PROPERTIES OF PLASMODIUM VIVAX DUFFY BINDING PROTEIN II ANTIBODIES ARE INFLUENCED BY HLA CLASS II ALLELIC VARIANTS
Autor(es)
Kano, Flora Satiko
Silva, Flavia Alessandra de Souza
Torres, Leticia de Menezes
Lima, Barbara Andreza Soares
Sousa, Taís Nóbrega de
Alves, Jéssica Rafaella dos Santos
Rocha, Roberto Sena
Fontes, Cor Jésus Fernandes
Sanchez, Bruno Antonio Marinho
Adams, John H.
Brito, Cristiana Ferreira Alves de
Pires, Douglas Eduardo Valente
Ascher, David Benjamin
Sell, Ana Maria
Carvalho, Luzia Helena de
Silva, Flavia Alessandra de Souza
Torres, Leticia de Menezes
Lima, Barbara Andreza Soares
Sousa, Taís Nóbrega de
Alves, Jéssica Rafaella dos Santos
Rocha, Roberto Sena
Fontes, Cor Jésus Fernandes
Sanchez, Bruno Antonio Marinho
Adams, John H.
Brito, Cristiana Ferreira Alves de
Pires, Douglas Eduardo Valente
Ascher, David Benjamin
Sell, Ana Maria
Carvalho, Luzia Helena de
Afiliação
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas Leônidas e Maria Deane., Manaus, AM, Brazil
Universidade Federal de Mato Grosso. Faculdade de Medicina. Cuiabá, MS, Brazil
Universidade Federal de Mato Grosso. Instituto de Ciências da Saúde. Sinop, MS, Brazil
University of South Florida. College of Public Health. Department of Global Health. Tampa, FL, United States of America
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/University of Cambridge. Department of Biochemistry. Cambridge, United Kingdom/University of Melbourne. Department of Biochemistry. Victoria, Australia
Universidade Estadual de Maringá. Programa de Pós-graduação em Biociências e Fisiopatologia. Maringá, PR, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas Leônidas e Maria Deane., Manaus, AM, Brazil
Universidade Federal de Mato Grosso. Faculdade de Medicina. Cuiabá, MS, Brazil
Universidade Federal de Mato Grosso. Instituto de Ciências da Saúde. Sinop, MS, Brazil
University of South Florida. College of Public Health. Department of Global Health. Tampa, FL, United States of America
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/University of Cambridge. Department of Biochemistry. Cambridge, United Kingdom/University of Melbourne. Department of Biochemistry. Victoria, Australia
Universidade Estadual de Maringá. Programa de Pós-graduação em Biociências e Fisiopatologia. Maringá, PR, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Resumo em Inglês
Background: The human malaria parasite Plasmodium vivax infects red blood cells through a key pathway that requires interaction between Duffy binding protein II (DBPII) and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC). A high proportion of P. vivax-exposed individuals fail to develop antibodies that inhibit DBPII-DARC interaction, and genetic factors that modulate this humoral immune response are poorly characterized. Here, we investigate if DBPII responsiveness could be HLA class II-linked.
Methodology/Principal Findings: A community-based open cohort study was carried out in an agricultural settlement of the Brazilian Amazon, in which 336 unrelated volunteers were genotyped for HLA class II (DRB1, DQA1 and DQB1 loci), and their DBPII immune responses were monitored over time (baseline, 6 and 12 months) by conventional serology (DBPII IgG ELISA-detected) and functional assays (inhibition of DBPII–erythrocyte binding). The results demonstrated an increased susceptibility of the DRB1*13:01 carriers to develop and sustain an anti-DBPII IgG response, while individuals with the haplotype DRB1*14:02-DQA1*05:03-DQB1*03:01 were persistent non-responders. HLA class II gene polymorphisms also influenced the functional properties of DBPII antibodies (BIAbs, binding inhibitory antibodies), with three alleles (DRB1*07:01, DQA1*02:01 and DQB1*02:02) comprising a single haplotype linked with the presence and persistence of the BIAbs response. Modelling the structural effects of the HLA-DRB1 variants revealed a number of differences in the peptide-binding groove, which is likely to lead to altered antigen binding and presentation profiles, and hence may explain the differences in subject responses.
Conclusions/Significance:The current study confirms the heritability of the DBPII antibody response, with genetic variation in HLA class II genes influencing both the development and persistence of IgG antibody responses. Cellular studies to increase knowledge of the binding affinities of DBPII peptides for class II molecules linked with good or poor antibody responses might lead to the development of strategies for controlling the type of helper T cells activated in response to DBPII.
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