03056nas a2200409 4500000000100000008004100001260004900042653001000091653001100101653002400112653000900136653002300145653002100168653001100189653001100200653002100211653001200232653000900244653001600253653002500269100001400294700002300308700001300331700001500344700001200359700001400371700001400385700001300399700001600412700001200428245011000440856005100550300001100601490000700612520201300619022001402632 2011 d c2011 DecbLEPRA Health in ActionaColchester10aAdult10aAfrica10aAntigens, Bacterial10aAsia10aBacterial Proteins10aEndemic Diseases10aFemale10aHumans10aInterferon-gamma10aleprosy10aMale10aMiddle Aged10aMycobacterium leprae1 aBobosha K1 aPloeg-van Schip JJ1 aZewdie M1 aSapkota BR1 aHagge D1 aFranken K1 aInbiale W1 aAseffa A1 aOttenhoff T1 aGeluk A00aImmunogenicity of Mycobacterium leprae unique antigens in leprosy endemic populations in Asia and Africa. uhttps://leprosyreview.org/article/82/4/44-5458 a445-580 v823 a

Ongoing transmission of leprosy is evident from the stable disease incidence in high burden areas. Tools for early detection of Mycobacterium leprae (M. leprae) infection, particularly in sub-clinically infected individuals, are urgently required to reduce transmission. Following the sequencing of the M. leprae genome, many M. leprae-unique candidate proteins have been identified, several of which have been tested for induction of M. leprae specific T cell responses in different leprosy endemic areas. In this study, 21 M. leprae-unique proteins and 10 peptide pools covering the complete sequence of five M. leprae-unique proteins (ML0576, ML1989, ML1990, ML2283, and ML2567) were evaluated in 160 individuals in Nepal and Ethiopia. These included: tuberculoid and borderline tuberculoid (TT/BT), borderline borderline and borderline lepromatous (BB/BL) leprosy patients; healthy household contacts (HHC); tuberculosis (TB) patients and endemic controls (EC). Immunogenicity of the proteins was determined by IFN-gamma secretion via stimulation of PBMC in 6 days lymphocyte stimulation tests (LST) or in whole blood assays (WBA). In LST, BB/BL patients (40%) responded to ML0573 and ML1601 whereas ML1604 was most immunogenic in TT/BT (35%) and HHC (36%). Additionally, significant numbers of EC displayed IFN-gamma production in response to ML0573 (54%), ML1601 (50%) and ML1604 (54%). TB patients on the other hand, hardly responded to any of the proteins except for ML1989. Comparison of IFN-gamma responses to ML0121, ML0141 and ML0188 for TT/BT patients showed specific increase in diluted 6 days WBA compared to the undiluted 24 hours WBA, whereas EC showed a reduced response in the diluted WBA, which may indicate detection of disease-specific responses in the 6 days WBA. In summary, identification of multiple M. leprae proteins inducing M. leprae-specific T cell responses in groups at high risk of developing leprosy may contribute to improve early detection for M. leprae infection.

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