Journal
JOURNAL OF IMMUNOLOGY
Volume 188, Issue 10, Pages 4782-4791Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1103452
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Funding
- Netherlands Leprosy Relief Foundation [ILEP 7.01.02.48]
- Turing Foundation as part of the Initiative for Diagnostic and Epidemiological Assays for Leprosy Consortium
- Order of Malta Grants for Leprosy Research
- Q.M. Gastmann-Wichers Foundation
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [R01 AI-082575]
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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-gamma was similar for all groups, excluding M. leprae/IFN-gamma as a diagnostic readout. By contrast, ML2478 and ML0840 induced high IFN-gamma concentrations in Bangladeshi EC, which were completely absent for South Korean controls. Importantly, ML2478/IFN-gamma 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-gamma. Analyses of additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concentrations of MCP-1, MIP-1 beta, and IL-1 beta in patients compared with EC, whereas IFN-inducible protein-10, like IFN-gamma, 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-gamma or IFN-inducible protein-10, and also shows that MCP-1, MIP-1 beta, and IL-1 beta can potentially distinguish pathogenic immune responses from those induced during asymptomatic exposure to M. leprae. The Journal of Immunology, 2012, 188: 4782-4791.
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