From genome-based in silico predictions to ex vivo verification of leprosy diagnosis

Annemieke Geluk, John S. Spencer, Kidist Bobosha, Maria C.V. Pessolani, Geraldo M.B. Pereira, Sayera Banu, Nadine Honoré, Stephen T. Reece, Murdo MacDonald, Bishwa Raj Sapkota, Chaman Ranjit, Kees L.M.C. Franken, Martha Zewdie, Abraham Aseffa, Rabia Hussain, Mariane M. Stefani, Sangnae Cho, Linda Oskam, Patrick J. Brennan, Hazel M. Dockrell

Research output: Contribution to journalArticle

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Abstract

The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking. The recent identification of M. leprae-unique genes has allowed the analysis of human T-cell responses to novel M. leprae antigens. Antigens with the most-promising diagnostic potential were tested for their ability to induce cytokine secretion by using peripheral blood mononuclear cells from leprosy patients and controls in five different areas where leprosy is endemic; 246 individuals from Brazil, Nepal, Bangladesh, Pakistan, and Ethiopia were analyzed for gamma interferon responses to five recombinant proteins (ML1989, ML1990, ML2283, ML2346, and ML2567) and 22 synthetic peptides. Of these, the M. leprae-unique protein ML1989 was the most frequently recognized and ML2283 the most specific for M. leprae infection/exposure, as only a limited number of tuberculosis patients responded to this antigen. However, all proteins were recognized by a significant number of controls in areas of endemicity. T-cell responses correlated with in vitro response to M. leprae, suggesting that healthy controls in areas where leprosy is endemic are exposed to M. leprae. Importantly, 50% of the healthy household contacts and 59% of the controls in areas of endemicity had no detectable immunoglobulin M antibodies to M. leprae-specific PGL-I but responded in T-cell assays to ≥1 M. leprae protein. T-cell responses specific for leprosy patients and healthy household contacts were observed for ML2283- and ML0126-derived peptides, indicating that M. leprae peptides hold potential as diagnostic tools. Future work should concentrate on the development of a sensitive and field-friendly assay and identification of additional peptides and proteins that can induce M. leprae-specific T-cell responses.

Original languageEnglish
Pages (from-to)352-359
Number of pages8
JournalClinical and Vaccine Immunology
Volume16
Issue number3
DOIs
Publication statusPublished - 2009 Mar 1

Fingerprint

Mycobacterium leprae
T-cells
Leprosy
Computer Simulation
Genes
Genome
Peptides
Antigens
Assays
Mycobacterium Infections
Proteins
T-Lymphocytes
Recombinant Proteins
Interferon-gamma
Immunoglobulin M
Blood
Cytokines
Asymptomatic Diseases
Antibodies
Nepal

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Geluk, A., Spencer, J. S., Bobosha, K., Pessolani, M. C. V., Pereira, G. M. B., Banu, S., ... Dockrell, H. M. (2009). From genome-based in silico predictions to ex vivo verification of leprosy diagnosis. Clinical and Vaccine Immunology, 16(3), 352-359. https://doi.org/10.1128/CVI.00414-08
Geluk, Annemieke ; Spencer, John S. ; Bobosha, Kidist ; Pessolani, Maria C.V. ; Pereira, Geraldo M.B. ; Banu, Sayera ; Honoré, Nadine ; Reece, Stephen T. ; MacDonald, Murdo ; Sapkota, Bishwa Raj ; Ranjit, Chaman ; Franken, Kees L.M.C. ; Zewdie, Martha ; Aseffa, Abraham ; Hussain, Rabia ; Stefani, Mariane M. ; Cho, Sangnae ; Oskam, Linda ; Brennan, Patrick J. ; Dockrell, Hazel M. / From genome-based in silico predictions to ex vivo verification of leprosy diagnosis. In: Clinical and Vaccine Immunology. 2009 ; Vol. 16, No. 3. pp. 352-359.
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abstract = "The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking. The recent identification of M. leprae-unique genes has allowed the analysis of human T-cell responses to novel M. leprae antigens. Antigens with the most-promising diagnostic potential were tested for their ability to induce cytokine secretion by using peripheral blood mononuclear cells from leprosy patients and controls in five different areas where leprosy is endemic; 246 individuals from Brazil, Nepal, Bangladesh, Pakistan, and Ethiopia were analyzed for gamma interferon responses to five recombinant proteins (ML1989, ML1990, ML2283, ML2346, and ML2567) and 22 synthetic peptides. Of these, the M. leprae-unique protein ML1989 was the most frequently recognized and ML2283 the most specific for M. leprae infection/exposure, as only a limited number of tuberculosis patients responded to this antigen. However, all proteins were recognized by a significant number of controls in areas of endemicity. T-cell responses correlated with in vitro response to M. leprae, suggesting that healthy controls in areas where leprosy is endemic are exposed to M. leprae. Importantly, 50{\%} of the healthy household contacts and 59{\%} of the controls in areas of endemicity had no detectable immunoglobulin M antibodies to M. leprae-specific PGL-I but responded in T-cell assays to ≥1 M. leprae protein. T-cell responses specific for leprosy patients and healthy household contacts were observed for ML2283- and ML0126-derived peptides, indicating that M. leprae peptides hold potential as diagnostic tools. Future work should concentrate on the development of a sensitive and field-friendly assay and identification of additional peptides and proteins that can induce M. leprae-specific T-cell responses.",
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Geluk, A, Spencer, JS, Bobosha, K, Pessolani, MCV, Pereira, GMB, Banu, S, Honoré, N, Reece, ST, MacDonald, M, Sapkota, BR, Ranjit, C, Franken, KLMC, Zewdie, M, Aseffa, A, Hussain, R, Stefani, MM, Cho, S, Oskam, L, Brennan, PJ & Dockrell, HM 2009, 'From genome-based in silico predictions to ex vivo verification of leprosy diagnosis', Clinical and Vaccine Immunology, vol. 16, no. 3, pp. 352-359. https://doi.org/10.1128/CVI.00414-08

From genome-based in silico predictions to ex vivo verification of leprosy diagnosis. / Geluk, Annemieke; Spencer, John S.; Bobosha, Kidist; Pessolani, Maria C.V.; Pereira, Geraldo M.B.; Banu, Sayera; Honoré, Nadine; Reece, Stephen T.; MacDonald, Murdo; Sapkota, Bishwa Raj; Ranjit, Chaman; Franken, Kees L.M.C.; Zewdie, Martha; Aseffa, Abraham; Hussain, Rabia; Stefani, Mariane M.; Cho, Sangnae; Oskam, Linda; Brennan, Patrick J.; Dockrell, Hazel M.

In: Clinical and Vaccine Immunology, Vol. 16, No. 3, 01.03.2009, p. 352-359.

Research output: Contribution to journalArticle

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AU - Zewdie, Martha

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Geluk A, Spencer JS, Bobosha K, Pessolani MCV, Pereira GMB, Banu S et al. From genome-based in silico predictions to ex vivo verification of leprosy diagnosis. Clinical and Vaccine Immunology. 2009 Mar 1;16(3):352-359. https://doi.org/10.1128/CVI.00414-08