Postgenomic approach to identify novel Mycobacterium leprae antigens with potential to improve immunodiagnosis of infection.
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.
Geluk
Annemieke
A
Department of Immunohematology and Blood Transfusion, LUMC PO Box 9600, 2300 RC Leiden, The Netherlands. a.geluk@lumc.nl
Klein
Michèl R
MR
Franken
Kees L M C
KL
van Meijgaarden
Krista E
KE
Wieles
Brigitte
B
Pereira
Kelly Cristina
KC
Bührer-Sékula
Samira
S
Klatser
Paul R
PR
Brennan
Patrick J
PJ
Spencer
John S
JS
Williams
Diana L
DL
Pessolani
Maria C V
MC
Sampaio
Elizabeth P
EP
Ottenhoff
Tom H M
TH
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
D000942:Antigens, Bacterial; D006017:Glycolipids; D007075:Immunoglobulin M; C045169:phenolic glycolipid I, Mycobacterium leprae