Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/18411
Type
ArticleCopyright
Open access
Collections
- IOC - Artigos de Periódicos [12507]
Metadata
Show full item record
NEW BIOMARKERS WITH RELEVANCE TO LEPROSY DIAGNOSIS APPLICABLE IN AREAS HYPERENDEMIC FOR LEPROSY
Author
Geluk, Annemieke
Bobosha, Kidist
van der Ploeg-van Schip, Jolien J.
Spencer, John S.
Banu, Sayera
Martins, Marcia V. S. B.
Cho, Sang-Nae
Franken, Kees L. M. C.
Kim, Hee Jin
Bekele, Yonas
Uddin, Mohammad K. M.
Hadi, Sheikh Abdul
Aseffa, Abraham
Pessolani, Maria C. V.
Pereira, Geraldo M. B.
Dockrell, Hazel M.
Ottenhoff, Tom H. M.
Bobosha, Kidist
van der Ploeg-van Schip, Jolien J.
Spencer, John S.
Banu, Sayera
Martins, Marcia V. S. B.
Cho, Sang-Nae
Franken, Kees L. M. C.
Kim, Hee Jin
Bekele, Yonas
Uddin, Mohammad K. M.
Hadi, Sheikh Abdul
Aseffa, Abraham
Pessolani, Maria C. V.
Pereira, Geraldo M. B.
Dockrell, Hazel M.
Ottenhoff, Tom H. M.
Affilliation
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands / Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Colorado State University. Department of Microbiology, Immunology, and Pathology. Fort Collins, CO, USA.
International Center for Diarrhoeal Disease Research Bangladesh. Dhaka 1000, Bangladesh.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil.
Yonsei University College of Medicine. Institute of Immunology and Immunological Diseases. Department of Microbiology. Seoul, LKorea.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Rio de Janeiro, RJ, Brasil.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
International Center for Diarrhoeal Disease Research Bangladesh. Dhaka 1000, Bangladesh.
International Center for Diarrhoeal Disease Research Bangladesh. Dhaka 1000, Bangladesh.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil.
Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Rio de Janeiro, RJ, Brasil.
London School of Hygiene and Tropical Medicine. London, United Kingdom.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands / Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Colorado State University. Department of Microbiology, Immunology, and Pathology. Fort Collins, CO, USA.
International Center for Diarrhoeal Disease Research Bangladesh. Dhaka 1000, Bangladesh.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil.
Yonsei University College of Medicine. Institute of Immunology and Immunological Diseases. Department of Microbiology. Seoul, LKorea.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Rio de Janeiro, RJ, Brasil.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
International Center for Diarrhoeal Disease Research Bangladesh. Dhaka 1000, Bangladesh.
International Center for Diarrhoeal Disease Research Bangladesh. Dhaka 1000, Bangladesh.
Armauer Hansen Research Institute. Addis Ababa, Ethiopia.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil.
Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Rio de Janeiro, RJ, Brasil.
London School of Hygiene and Tropical Medicine. London, United Kingdom.
Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands.
Abstract
Leprosy is not eradicable with currently available diagnostics or interventions, as evidenced by its stable incidence. Early diagnosis of Mycobacterium leprae infection should therefore be emphasized in leprosy research. It remains challenging to develop tests based on immunological biomarkers that distinguish individuals controlling bacterial replication from those developing disease. To identify biomarkers for field-applicable diagnostics, we determined cytokines/chemokines induced by M. leprae proteins in blood of leprosy patients and endemic controls (EC) from high leprosy-prevalence areas (Bangladesh, Brazil, Ethiopia) and from South Korea, where leprosy is not endemic anymore. M. leprae-sonicate-induced IFN-γ was similar for all groups, excluding M. leprae/IFN-γ as a diagnostic readout. By contrast, ML2478 and ML0840 induced high IFN-γ concentrations in Bangladeshi EC, which were completely absent for South Korean controls. Importantly, ML2478/IFN-γ could indicate distinct degrees of M. leprae exposure, and thereby the risk of infection and transmission, in different parts of Brazilian and Ethiopian cities. Notwithstanding these discriminatory responses, M. leprae proteins did not distinguish patients from EC in one leprosy-endemic area based on IFN-γ. Analyses of additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concentrations of MCP-1, MIP-1β, and IL-1β in patients compared with EC, whereas IFN-inducible protein-10, like IFN-γ, differed between EC from areas with dissimilar leprosy prevalence. This study identifies M. leprae-unique Ags, particularly ML2478, as biomarker tools to measure M. leprae exposure using IFN-γ or IFN-inducible protein-10, and also shows that MCP-1, MIP-1β, and IL-1β can potentially distinguish pathogenic immune responses from those induced during asymptomatic exposure to M. leprae.
Share