title: Postgenomic approach to identify novel Mycobacterium leprae antigens with potential to improve immunodiagnosis of infection.
abstract: Early detection of Mycobacterium leprae infection is considered an important component of strategies aiming at reducing transmission of infection, but currently available diagnostic tools often lack sufficient sensitivity and specificity to reach this goal. Recent comparative genomics have revealed the presence of 165 M. leprae genes with no homologue in M. tuberculosis. We selected 17 of these genes for further study. All 17 genes were found to be expressed at the mRNA level in M. leprae from infected mice and from a multibacillary leprosy patient. Additional comparative genomic analyses of all currently available mycobacterial genome databases confirmed 12 candidate genes to be unique to M. leprae, whereas 5 genes had homologues in mycobacteria other than M. tuberculosis. Evaluation of the immunogenicity of all 17 recombinant proteins in PBMC from 127 Brazilians showed that five antigens (ML0576, ML1989, ML1990, ML2283, and ML2567) induced significant gamma interferon levels in paucibacillary leprosy patients, reactional leprosy patients, and exposed healthy controls but not in most multibacillary leprosy patients, tuberculosis patients, or endemic controls. Importantly, among exposed healthy controls 71% had no detectable immunoglobulin M antibodies to the M. leprae-specific PGL-I but responded to one or more M. leprae antigen(s). Collectively, the M. leprae proteins identified are expressed at the transcriptome level and can efficiently activate T cells of M. leprae-exposed individuals. These proteins may provide new tools to develop tests for specific diagnosis of M. leprae infection and may enhance our understanding of leprosy and its transmission.
authors.affiliation: Department of Immunohematology and Blood Transfusion, LUMC PO Box 9600, 2300 RC Leiden, The Netherlands. a.geluk@lumc.nl
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.forename: Michèl R
authors.initials: MR
authors.lastname: Klein
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wieles
authors.forename: Kelly Cristina
authors.initials: KC
authors.lastname: Pereira
authors.forename: Samira
authors.initials: S
authors.lastname: Bührer-Sékula
authors.forename: Paul R
authors.initials: PR
authors.lastname: Klatser
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: John S
authors.initials: JS
authors.lastname: Spencer
authors.forename: Diana L
authors.initials: DL
authors.lastname: Williams
authors.forename: Maria C V
authors.initials: MC
authors.lastname: Pessolani
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Sampaio
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D016680:Genome, Bacterial; D006017:Glycolipids / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007918:Leprosy / Q000175:diagnosis* / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008819:Mice, Nude; D009166:Mycobacterium leprae / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D006017:Glycolipids; D007075:Immunoglobulin M; C045169:phenolic glycolipid I, Mycobacterium leprae