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 fromareas 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. Copyright
| Original language | English |
|---|---|
| Pages (from-to) | 4782-4791 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 188 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2012 May 15 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
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New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy. / Geluk, Annemieke; Bobosha, Kidist; Van Der Ploeg-van Schip, Jolien J.; Spencer, John S.; Banu, Sayera; Martins, Marcia V.S.B.; Cho, Sangnae; 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.
In: Journal of Immunology, Vol. 188, No. 10, 15.05.2012, p. 4782-4791.Research output: Contribution to journal › Article
TY - JOUR
T1 - New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy
AU - Geluk, Annemieke
AU - Bobosha, Kidist
AU - Van Der Ploeg-van Schip, Jolien J.
AU - Spencer, John S.
AU - Banu, Sayera
AU - Martins, Marcia V.S.B.
AU - Cho, Sangnae
AU - Franken, Kees L.M.C.
AU - Kim, Hee Jin
AU - Bekele, Yonas
AU - Uddin, Mohammad K.M.
AU - Hadi, Sheikh Abdul
AU - Aseffa, Abraham
AU - Pessolani, Maria C.V.
AU - Pereira, Geraldo M.B.
AU - Dockrell, Hazel M.
AU - Ottenhoff, Tom H.M.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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 fromareas 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. Copyright
AB - 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 fromareas 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. Copyright
UR - http://www.scopus.com/inward/record.url?scp=84861122390&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861122390&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1103452
DO - 10.4049/jimmunol.1103452
M3 - Article
C2 - 22504648
AN - SCOPUS:84861122390
VL - 188
SP - 4782
EP - 4791
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -