03063nas a2200409 4500000000100000008004100001260004900042653001000091653001100101653002400112653000900136653002300145653002100168653001100189653001100200653002100211653001200232653000900244653001600253653001500269100001200284700001400296700001600310700001300326700001500339700001200354700001400366700001300380700002300393700001400416245011000430856006800540300001100608490000700619520201300626022001402639 2011 d c2011 DecbLEPRA Health in ActionaColchester10aAdult10aAfrica10aAntigens, Bacterial10aAsia10aBacterial Proteins10aEndemic Diseases10aFemale10aHumans10aInterferon-gamma10aleprosy10aMale10aMiddle Aged10atratamento1 aGeluk A1 aFranken K1 aOttenhoff T1 aAseffa A1 aSapkota BR1 aHagge D1 aBobosha K1 aZewdie M1 aPloeg-van Schip JJ1 aInbiale W00aImmunogenicity of Mycobacterium leprae unique antigens in leprosy endemic populations in Asia and Africa. uhttp://www.lepra.org.uk/platforms/lepra/files/lr/Dec11/1693.pdf 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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