New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy

Annemieke Geluk, Kidist Bobosha, Jolien J. Van Der Ploeg-van Schip, John S. Spencer, Sayera Banu, Marcia V.S.B. Martins, Sangnae Cho, Kees L.M.C. Franken, Hee Jin Kim, Yonas Bekele, Mohammad K.M. Uddin, Sheikh Abdul Hadi, Abraham Aseffa, Maria C.V. Pessolani, Geraldo M.B. Pereira, Hazel M. Dockrell, Tom H.M. Ottenhoff

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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 languageEnglish
Pages (from-to)4782-4791
Number of pages10
JournalJournal of Immunology
Volume188
Issue number10
DOIs
Publication statusPublished - 2012 May 15

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Mycobacterium leprae
Leprosy
Biomarkers
Interleukin-1
Chemokines
Cytokines
Republic of Korea
Mycobacterium Infections
Proteins
Infectious Disease Transmission
Ethiopia
Bangladesh
Brazil
Blood Proteins
Early Diagnosis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Geluk, A., Bobosha, K., Van Der Ploeg-van Schip, J. J., Spencer, J. S., Banu, S., Martins, M. V. S. B., ... Ottenhoff, T. H. M. (2012). New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy. Journal of Immunology, 188(10), 4782-4791. https://doi.org/10.4049/jimmunol.1103452
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. / New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy. In: Journal of Immunology. 2012 ; Vol. 188, No. 10. pp. 4782-4791.
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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",
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Geluk, A, Bobosha, K, Van Der Ploeg-van Schip, JJ, Spencer, JS, Banu, S, Martins, MVSB, Cho, S, Franken, KLMC, Kim, HJ, Bekele, Y, Uddin, MKM, Hadi, SA, Aseffa, A, Pessolani, MCV, Pereira, GMB, Dockrell, HM & Ottenhoff, THM 2012, 'New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy', Journal of Immunology, vol. 188, no. 10, pp. 4782-4791. https://doi.org/10.4049/jimmunol.1103452

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 journalArticle

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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.

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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

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Geluk A, Bobosha K, Van Der Ploeg-van Schip JJ, Spencer JS, Banu S, Martins MVSB et al. New biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy. Journal of Immunology. 2012 May 15;188(10):4782-4791. https://doi.org/10.4049/jimmunol.1103452