02713nas a2200457 4500000000100000008004100001260001300042653001500055653001000070653000900080653002400089653002300113653001100136653002000147653001100167653001100178653002100189653001200210653000900222653001600231653002500247653002500272653001800297100001300315700001100328700001300339700001300352700001500365700001500380700001300395700001500408700001400423700001100437245005900448856007200507300001200579490000700591050001600598520162700614022001402241 2008 d c2008 Nov10aAdolescent10aAdult10aAged10aAntigens, Bacterial10aBacterial Proteins10aBrazil10aCells, Cultured10aFemale10aHumans10aInterferon-gamma10aleprosy10aMale10aMiddle Aged10aMycobacterium leprae10aRecombinant Proteins10aT-Lymphocytes1 aDuthie M1 aGoto W1 aIreton G1 aReece ST1 aSampaio LS1 aGrassi A B1 aSousa AL1 aMartelli C1 aStefani M1 aReed S00aAntigen-specific T-cell responses of leprosy patients. uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583521/pdf/0234-08.pdf a1659-650 v15 aDUTHIE 20083 a
The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-gamma) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in GoiĆ¢nia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-gamma, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-gamma) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.
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