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ANTIBODY PROFILING IN PATIENTS WITH MILD AND SEVERE LEPTOSPIROSIS: A GENOME-WIDE PROTEIN MICROARRAY APPROACH
Autor(es)
Afiliação
Fiocruz. Brazilian Ministry of Health. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA
Antigen Discovery Inc. Irvine, CA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
Fiocruz. Brazilian Ministry of Health. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA
Antigen Discovery Inc. Irvine, CA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA
University of California Irvine McGaugh Hall. Division of Infectious Disease. Department of Medicine. Irvine, California, USA
Fiocruz. Brazilian Ministry of Health. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil
Resumo em Inglês
Leptospirosis is zoonotic disease of global importance, with over a million cases
and nearly 60,000 deaths annually. Symptomatic disease presentation ranges
from a mild febrile disease with non-specific symptoms to severe forms,
characterized by multi-organ failure, lung hemorrhage, and death. Factors
governing severe outcomes remain unclear, but the host immune response likely
plays an important role. In the present study, we used protein microarray chip to
identify the antibody profiles of patients with severe and mild leptospirosis against
the complete Leptospira interrogans serovar Copenhageni predicted ORFeome.
We discovered a limited number of immunodominant antigens, with 36 antigens
specific to patients. Of these, 11 were identified during acute phase, which are
therefore potential serodiagnostic antigens while 33 were detected after recovery
and are potential subunit vaccine targets. Surprisingly, we found the antibody
repertoire varies in patients with different clinical outcomes: in the severe group,
overall IgM responses do not change and IgG responses increase over time, while
both IgM and IgG responses remain relatively the same in the mild patient group.
By analyzing antibody responses by individual patient, we observed that over 74%
of patients with severe symptoms compared to 29% of patients with mild
leptospirosis had significant IgG increases over time. Additionally, 90.0% of IgM
responses did not change over time in the mild group, compared to 51.6% in the
severe group. Thus, we hypothesized that patients with mild symptoms were
protected from severe disease due to pre-existing antibodies, while the profile of
patients with severe outcomes was representative of a first exposure. These
findings represent a substantial step forward in the knowledge of the humoral
immune response to Leptospira infection, and we have identified new targets for
vaccine and diagnostic test development
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