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IDENTIFICATION OF SEROREACTIVE PROTEINS OF LEPTOSPIRA INTERROGANS SEROVAR COPENHAGENI USING A HIGH-DENSITY PROTEIN MICROARRAY APPROACH
Leptospira interrogans
Sorodiagnóstico
Diagnóstico
Antibiótico
Proteína
Transmissão
Humanos
Antígenos
Author
Aquino, Carolina Lessa
Rodrigues, Camila Borges
Pablo, Jozelyn
Sasaki, Rie
Jasinskas, Algis
Liang, Li
Wunder Junior, Elsio Augusto
Ribeiro, Guilherme de Sousa
Vigil, Adam
Galler, Ricardo
Molina, Douglas
Liang, Xiaowu
Reis, Mitermayer Galvão dos
Ko, Albert Icksang
Medeiros, Marco Alberto
Felgner, Philip L.
Rodrigues, Camila Borges
Pablo, Jozelyn
Sasaki, Rie
Jasinskas, Algis
Liang, Li
Wunder Junior, Elsio Augusto
Ribeiro, Guilherme de Sousa
Vigil, Adam
Galler, Ricardo
Molina, Douglas
Liang, Xiaowu
Reis, Mitermayer Galvão dos
Ko, Albert Icksang
Medeiros, Marco Alberto
Felgner, Philip L.
Affilliation
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil / University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil / University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA / Antigen Discovery Inc. Irvine, CA, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
United States of America. Department of Epidemiology of Microbial Diseases. Yale University, New Haven, Connecticut
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil / University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA / Antigen Discovery Inc. Irvine, CA, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
United States of America. Department of Epidemiology of Microbial Diseases. Yale University, New Haven, Connecticut
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Bio-Manguinhos. Brazilian Ministry of Health. Rio de Janeiro, RJ, Brasil
University of California Irvine. Department of Medicine. Division of Infectious Disease. Irvine, California, USA
Abstract
Leptospirosis is a widespread zoonotic disease worldwide. The lack of an adequate laboratory test is a major barrier for diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. METHODOLOGY: In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response from 274 individuals, including 80 acute-phase, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic, and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. PRINCIPAL FINDINGS: We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL, and Loa22 are already known to be recognized by sera from human patients, thus serving as proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. CONCLUSIONS: Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection, and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the utility of these antigens in more deployable diagnostic platforms.
Keywords in Portuguese
LeptospiroseLeptospira interrogans
Sorodiagnóstico
Diagnóstico
Antibiótico
Proteína
Transmissão
Humanos
Antígenos
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