Antigen discovery

A postgenomic approach to leprosy diagnosis

Romulo Aráoz, Nadine Honoré, Sungae Cho, Jong Pill Kim, Sangnae Cho, Marc Monot, Caroline Demangel, Patrick J. Brennan, Stewart T. Cole

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Leprosy is an infectious, neurodegenerative disease of humans caused by Mycobacterium leprae. Despite effective control programs, the incidence of leprosy remains stubbornly high, suggesting that transmission may be more common than expected. The rationale of this work was to use bioinformatics and comparative genomics to identify potentially antigenic proteins for diagnostic purposes. This approach defined three classes of proteins: those restricted to M. leprae (class I), those present in M. leprae with orthologues in other organisms besides mycobacteria (class II), and exported or surface-exposed proteins (class III). Twelve genes (two class I, four class II, and six class III proteins) were cloned in Escherichia coli, and their protein products were purified. Six of these proteins were detected in cell extracts of M. leprae by immunoblotting. The immunogenicity of each recombinant protein was then investigated in leprosy patients by measuring the reactivity of circulating antibody and gamma interferon (IFN-γ) responses in T-cell restimulation assays. Several class II and class III proteins were recognized by circulating antibodies. Importantly, most class II proteins elicited IFN-γ responses that were significantly stronger than those produced by previously identified antigens. Among them, two class II proteins, ML0308 and ML2498, showed marked humoral and cellular immunogenicity, therefore providing promising candidates for the diagnosis of both tuberculoid and lepromatous forms of leprosy.

Original languageEnglish
Pages (from-to)175-182
Number of pages8
JournalInfection and Immunity
Volume74
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1

Fingerprint

Leprosy
Mycobacterium leprae
Antigens
Proteins
MHC Class I Genes
Lepromatous Leprosy
Antibodies
Escherichia coli Proteins
Mycobacterium
Genomics
Cell Extracts
Computational Biology
Recombinant Proteins
Immunoblotting
Neurodegenerative Diseases
Interferons
Interferon-gamma
Communicable Diseases
Membrane Proteins
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Aráoz, R., Honoré, N., Cho, S., Kim, J. P., Cho, S., Monot, M., ... Cole, S. T. (2006). Antigen discovery: A postgenomic approach to leprosy diagnosis. Infection and Immunity, 74(1), 175-182. https://doi.org/10.1128/IAI.74.1.175-182.2006
Aráoz, Romulo ; Honoré, Nadine ; Cho, Sungae ; Kim, Jong Pill ; Cho, Sangnae ; Monot, Marc ; Demangel, Caroline ; Brennan, Patrick J. ; Cole, Stewart T. / Antigen discovery : A postgenomic approach to leprosy diagnosis. In: Infection and Immunity. 2006 ; Vol. 74, No. 1. pp. 175-182.
@article{ab5a532de2cf439c8fd1526ba7120484,
title = "Antigen discovery: A postgenomic approach to leprosy diagnosis",
abstract = "Leprosy is an infectious, neurodegenerative disease of humans caused by Mycobacterium leprae. Despite effective control programs, the incidence of leprosy remains stubbornly high, suggesting that transmission may be more common than expected. The rationale of this work was to use bioinformatics and comparative genomics to identify potentially antigenic proteins for diagnostic purposes. This approach defined three classes of proteins: those restricted to M. leprae (class I), those present in M. leprae with orthologues in other organisms besides mycobacteria (class II), and exported or surface-exposed proteins (class III). Twelve genes (two class I, four class II, and six class III proteins) were cloned in Escherichia coli, and their protein products were purified. Six of these proteins were detected in cell extracts of M. leprae by immunoblotting. The immunogenicity of each recombinant protein was then investigated in leprosy patients by measuring the reactivity of circulating antibody and gamma interferon (IFN-γ) responses in T-cell restimulation assays. Several class II and class III proteins were recognized by circulating antibodies. Importantly, most class II proteins elicited IFN-γ responses that were significantly stronger than those produced by previously identified antigens. Among them, two class II proteins, ML0308 and ML2498, showed marked humoral and cellular immunogenicity, therefore providing promising candidates for the diagnosis of both tuberculoid and lepromatous forms of leprosy.",
author = "Romulo Ar{\'a}oz and Nadine Honor{\'e} and Sungae Cho and Kim, {Jong Pill} and Sangnae Cho and Marc Monot and Caroline Demangel and Brennan, {Patrick J.} and Cole, {Stewart T.}",
year = "2006",
month = "1",
day = "1",
doi = "10.1128/IAI.74.1.175-182.2006",
language = "English",
volume = "74",
pages = "175--182",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "1",

}

Aráoz, R, Honoré, N, Cho, S, Kim, JP, Cho, S, Monot, M, Demangel, C, Brennan, PJ & Cole, ST 2006, 'Antigen discovery: A postgenomic approach to leprosy diagnosis', Infection and Immunity, vol. 74, no. 1, pp. 175-182. https://doi.org/10.1128/IAI.74.1.175-182.2006

Antigen discovery : A postgenomic approach to leprosy diagnosis. / Aráoz, Romulo; Honoré, Nadine; Cho, Sungae; Kim, Jong Pill; Cho, Sangnae; Monot, Marc; Demangel, Caroline; Brennan, Patrick J.; Cole, Stewart T.

In: Infection and Immunity, Vol. 74, No. 1, 01.01.2006, p. 175-182.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antigen discovery

T2 - A postgenomic approach to leprosy diagnosis

AU - Aráoz, Romulo

AU - Honoré, Nadine

AU - Cho, Sungae

AU - Kim, Jong Pill

AU - Cho, Sangnae

AU - Monot, Marc

AU - Demangel, Caroline

AU - Brennan, Patrick J.

AU - Cole, Stewart T.

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Leprosy is an infectious, neurodegenerative disease of humans caused by Mycobacterium leprae. Despite effective control programs, the incidence of leprosy remains stubbornly high, suggesting that transmission may be more common than expected. The rationale of this work was to use bioinformatics and comparative genomics to identify potentially antigenic proteins for diagnostic purposes. This approach defined three classes of proteins: those restricted to M. leprae (class I), those present in M. leprae with orthologues in other organisms besides mycobacteria (class II), and exported or surface-exposed proteins (class III). Twelve genes (two class I, four class II, and six class III proteins) were cloned in Escherichia coli, and their protein products were purified. Six of these proteins were detected in cell extracts of M. leprae by immunoblotting. The immunogenicity of each recombinant protein was then investigated in leprosy patients by measuring the reactivity of circulating antibody and gamma interferon (IFN-γ) responses in T-cell restimulation assays. Several class II and class III proteins were recognized by circulating antibodies. Importantly, most class II proteins elicited IFN-γ responses that were significantly stronger than those produced by previously identified antigens. Among them, two class II proteins, ML0308 and ML2498, showed marked humoral and cellular immunogenicity, therefore providing promising candidates for the diagnosis of both tuberculoid and lepromatous forms of leprosy.

AB - Leprosy is an infectious, neurodegenerative disease of humans caused by Mycobacterium leprae. Despite effective control programs, the incidence of leprosy remains stubbornly high, suggesting that transmission may be more common than expected. The rationale of this work was to use bioinformatics and comparative genomics to identify potentially antigenic proteins for diagnostic purposes. This approach defined three classes of proteins: those restricted to M. leprae (class I), those present in M. leprae with orthologues in other organisms besides mycobacteria (class II), and exported or surface-exposed proteins (class III). Twelve genes (two class I, four class II, and six class III proteins) were cloned in Escherichia coli, and their protein products were purified. Six of these proteins were detected in cell extracts of M. leprae by immunoblotting. The immunogenicity of each recombinant protein was then investigated in leprosy patients by measuring the reactivity of circulating antibody and gamma interferon (IFN-γ) responses in T-cell restimulation assays. Several class II and class III proteins were recognized by circulating antibodies. Importantly, most class II proteins elicited IFN-γ responses that were significantly stronger than those produced by previously identified antigens. Among them, two class II proteins, ML0308 and ML2498, showed marked humoral and cellular immunogenicity, therefore providing promising candidates for the diagnosis of both tuberculoid and lepromatous forms of leprosy.

UR - http://www.scopus.com/inward/record.url?scp=29644440605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29644440605&partnerID=8YFLogxK

U2 - 10.1128/IAI.74.1.175-182.2006

DO - 10.1128/IAI.74.1.175-182.2006

M3 - Article

VL - 74

SP - 175

EP - 182

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 1

ER -