02885nas a2200457   4500000000100000008004100001260001300042653001200055653002400067653002200091653001600113653001100129653002100140653001200161653000900173653001500182653002500197653003000222653001800252100001200270700001200282700001400294700001800308700001300326700001500339700002200354700001400376700001500390700001500405700001600420700001900436700001400455700001600469245012900485856007200614300001200686490000700698050001400705520169400719022001402413       2005                            d  c2005 Sep10aAnimals10aAntigens, Bacterial10aGenome, Bacterial10aGlycolipids10aHumans10aImmunoglobulin M10aleprosy10aMice10aMice, Nude10aMycobacterium leprae10apolymerase chain reaction10aT-Lymphocytes1 aGeluk A1 aKlein M1 aFranken K1 aMeijgaarden K1 aWieles B1 aPereira KC1 aBührer-Sékula S1 aKlatser P1 aBrennan PJ1 aSpencer JS1 aWilliams DL1 aPessolani MC V1 aSampaio E1 aOttenhoff T00aPostgenomic approach to identify novel Mycobacterium leprae antigens with potential to improve immunodiagnosis of infection.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1231107/pdf/0482-05.pdf  a5636-440 v73  aGELUK20053 a<p>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.</p>  a0019-9567