Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy

John S. Spencer, Hazel M. Dockrell, Hee Jin Kim, Maria A.M. Marques, Diana L. Williams, Marcia V.S.B. Martins, Marcio L.F. Martins, Monica C.B.S. Lima, Euzenir N. Sarno, Geraldo M.B. Pereira, Haroldo Matos, Leila S. Fonseca, Elisabeth P. Sampaio, Thomas H.M. Ottenhoff, Annemieke Geluk, Sangnae Cho, Neil G. Stoker, Stewart T. Cole, Patrick J. Brennan, Maria C.V. Pessolani

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Abstract

Diagnosis of leprosy is a major obstacle to disease control and has been compromised in the past due to the lack of specific reagents. We have used comparative genome analysis to identify genes that are specific to Mycobacterium leprae and tested both recombinant proteins and synthetic peptides from a subset of these for immunological reactivity. Four unique recombinant proteins (ML0008, ML0126, ML1057, and ML2567) and a panel of 58 peptides (15 and 9 mer) were tested for IFN-γ responses in PBMC from leprosy patients and contacts, tuberculosis patients, and endemic and nonendemic controls. The responses to the four recombinant proteins gave higher levels of IFN-γ production, but less specificity, than the peptides. Thirty-five peptides showed IFN-γ responses only in the paucibacillary leprosy and household contact groups, with no responses in the tuberculosis or endemic control groups. High frequencies of IFN-γ-producing CD4+ and CD8+ T cells specific for the 15- and 9-mer peptides were observed in the blood of a paucibacillary leprosy patient. 9-mer peptides preferentially activated CD8 + T cells, while the 15-mer peptides were efficient in inducing responses in both the CD4+ and CD8+ T cell subsets. Four of the six 9-mer peptides tested showed promising specificity, indicating that CD8+ T cell epitopes may also have diagnostic potential. Those peptides that provide specific responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known.

Original languageEnglish
Pages (from-to)7930-7938
Number of pages9
JournalJournal of Immunology
Volume175
Issue number12
DOIs
Publication statusPublished - 2005 Dec 15

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Mycobacterium leprae
Leprosy
Peptides
Proteins
Paucibacillary Leprosy
Recombinant Proteins
Tuberculosis
T-Lymphocytes
Mycobacterium Infections
T-Lymphocyte Epitopes
T-Lymphocyte Subsets
Routine Diagnostic Tests
Genome
Control Groups

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Spencer, J. S., Dockrell, H. M., Kim, H. J., Marques, M. A. M., Williams, D. L., Martins, M. V. S. B., ... Pessolani, M. C. V. (2005). Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy. Journal of Immunology, 175(12), 7930-7938. https://doi.org/10.4049/jimmunol.175.12.7930
Spencer, John S. ; Dockrell, Hazel M. ; Kim, Hee Jin ; Marques, Maria A.M. ; Williams, Diana L. ; Martins, Marcia V.S.B. ; Martins, Marcio L.F. ; Lima, Monica C.B.S. ; Sarno, Euzenir N. ; Pereira, Geraldo M.B. ; Matos, Haroldo ; Fonseca, Leila S. ; Sampaio, Elisabeth P. ; Ottenhoff, Thomas H.M. ; Geluk, Annemieke ; Cho, Sangnae ; Stoker, Neil G. ; Cole, Stewart T. ; Brennan, Patrick J. ; Pessolani, Maria C.V. / Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy. In: Journal of Immunology. 2005 ; Vol. 175, No. 12. pp. 7930-7938.
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abstract = "Diagnosis of leprosy is a major obstacle to disease control and has been compromised in the past due to the lack of specific reagents. We have used comparative genome analysis to identify genes that are specific to Mycobacterium leprae and tested both recombinant proteins and synthetic peptides from a subset of these for immunological reactivity. Four unique recombinant proteins (ML0008, ML0126, ML1057, and ML2567) and a panel of 58 peptides (15 and 9 mer) were tested for IFN-γ responses in PBMC from leprosy patients and contacts, tuberculosis patients, and endemic and nonendemic controls. The responses to the four recombinant proteins gave higher levels of IFN-γ production, but less specificity, than the peptides. Thirty-five peptides showed IFN-γ responses only in the paucibacillary leprosy and household contact groups, with no responses in the tuberculosis or endemic control groups. High frequencies of IFN-γ-producing CD4+ and CD8+ T cells specific for the 15- and 9-mer peptides were observed in the blood of a paucibacillary leprosy patient. 9-mer peptides preferentially activated CD8 + T cells, while the 15-mer peptides were efficient in inducing responses in both the CD4+ and CD8+ T cell subsets. Four of the six 9-mer peptides tested showed promising specificity, indicating that CD8+ T cell epitopes may also have diagnostic potential. Those peptides that provide specific responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known.",
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Spencer, JS, Dockrell, HM, Kim, HJ, Marques, MAM, Williams, DL, Martins, MVSB, Martins, MLF, Lima, MCBS, Sarno, EN, Pereira, GMB, Matos, H, Fonseca, LS, Sampaio, EP, Ottenhoff, THM, Geluk, A, Cho, S, Stoker, NG, Cole, ST, Brennan, PJ & Pessolani, MCV 2005, 'Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy', Journal of Immunology, vol. 175, no. 12, pp. 7930-7938. https://doi.org/10.4049/jimmunol.175.12.7930

Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy. / Spencer, John S.; Dockrell, Hazel M.; Kim, Hee Jin; Marques, Maria A.M.; Williams, Diana L.; Martins, Marcia V.S.B.; Martins, Marcio L.F.; Lima, Monica C.B.S.; Sarno, Euzenir N.; Pereira, Geraldo M.B.; Matos, Haroldo; Fonseca, Leila S.; Sampaio, Elisabeth P.; Ottenhoff, Thomas H.M.; Geluk, Annemieke; Cho, Sangnae; Stoker, Neil G.; Cole, Stewart T.; Brennan, Patrick J.; Pessolani, Maria C.V.

In: Journal of Immunology, Vol. 175, No. 12, 15.12.2005, p. 7930-7938.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy

AU - Spencer, John S.

AU - Dockrell, Hazel M.

AU - Kim, Hee Jin

AU - Marques, Maria A.M.

AU - Williams, Diana L.

AU - Martins, Marcia V.S.B.

AU - Martins, Marcio L.F.

AU - Lima, Monica C.B.S.

AU - Sarno, Euzenir N.

AU - Pereira, Geraldo M.B.

AU - Matos, Haroldo

AU - Fonseca, Leila S.

AU - Sampaio, Elisabeth P.

AU - Ottenhoff, Thomas H.M.

AU - Geluk, Annemieke

AU - Cho, Sangnae

AU - Stoker, Neil G.

AU - Cole, Stewart T.

AU - Brennan, Patrick J.

AU - Pessolani, Maria C.V.

PY - 2005/12/15

Y1 - 2005/12/15

N2 - Diagnosis of leprosy is a major obstacle to disease control and has been compromised in the past due to the lack of specific reagents. We have used comparative genome analysis to identify genes that are specific to Mycobacterium leprae and tested both recombinant proteins and synthetic peptides from a subset of these for immunological reactivity. Four unique recombinant proteins (ML0008, ML0126, ML1057, and ML2567) and a panel of 58 peptides (15 and 9 mer) were tested for IFN-γ responses in PBMC from leprosy patients and contacts, tuberculosis patients, and endemic and nonendemic controls. The responses to the four recombinant proteins gave higher levels of IFN-γ production, but less specificity, than the peptides. Thirty-five peptides showed IFN-γ responses only in the paucibacillary leprosy and household contact groups, with no responses in the tuberculosis or endemic control groups. High frequencies of IFN-γ-producing CD4+ and CD8+ T cells specific for the 15- and 9-mer peptides were observed in the blood of a paucibacillary leprosy patient. 9-mer peptides preferentially activated CD8 + T cells, while the 15-mer peptides were efficient in inducing responses in both the CD4+ and CD8+ T cell subsets. Four of the six 9-mer peptides tested showed promising specificity, indicating that CD8+ T cell epitopes may also have diagnostic potential. Those peptides that provide specific responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known.

AB - Diagnosis of leprosy is a major obstacle to disease control and has been compromised in the past due to the lack of specific reagents. We have used comparative genome analysis to identify genes that are specific to Mycobacterium leprae and tested both recombinant proteins and synthetic peptides from a subset of these for immunological reactivity. Four unique recombinant proteins (ML0008, ML0126, ML1057, and ML2567) and a panel of 58 peptides (15 and 9 mer) were tested for IFN-γ responses in PBMC from leprosy patients and contacts, tuberculosis patients, and endemic and nonendemic controls. The responses to the four recombinant proteins gave higher levels of IFN-γ production, but less specificity, than the peptides. Thirty-five peptides showed IFN-γ responses only in the paucibacillary leprosy and household contact groups, with no responses in the tuberculosis or endemic control groups. High frequencies of IFN-γ-producing CD4+ and CD8+ T cells specific for the 15- and 9-mer peptides were observed in the blood of a paucibacillary leprosy patient. 9-mer peptides preferentially activated CD8 + T cells, while the 15-mer peptides were efficient in inducing responses in both the CD4+ and CD8+ T cell subsets. Four of the six 9-mer peptides tested showed promising specificity, indicating that CD8+ T cell epitopes may also have diagnostic potential. Those peptides that provide specific responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known.

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