03169nas a2200433   4500000000100000008004100001260001300042653002400055653002400079653002300103653001100126653001700137653001100154653002100165653001200186653002600198653002800224653002500252653001600277653001300293653003200306653001800338100001200356700001200368700001200380700001400392700001200406700001700418700001200435700001400447700001600461245015500477856007200632300001100704490000700715050001500722520198400737022001402721       2008                            d  c2008 Mar10aAmino Acid Sequence10aAntigens, Bacterial10aBacterial Proteins10aBrazil10aHLA Antigens10aHumans10aInterferon-gamma10aleprosy10aLymphocyte Activation10aMolecular Sequence Data10aMycobacterium leprae10aNetherlands10aPeptides10aSensitivity and Specificity10aT-Lymphocytes1 aGeluk A1 aPloeg J1 aTeles R1 aFranken K1 aPrins C1 aDrijfhout JW1 aSarno E1 aSampaio E1 aOttenhoff T00aRational combination of peptides derived from different Mycobacterium leprae proteins improves sensitivity for immunodiagnosis of M. leprae infection.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268264/pdf/0432-07.pdf  a522-330 v15  aGELUK 20083 a<p>The stable incidence of new leprosy cases suggests that transmission of infection is continuing despite the worldwide implementation of multidrug therapy programs. Highly specific tools are required to accurately diagnose asymptomatic and early stage Mycobacterium leprae infections which are the likely sources of transmission and cannot be identified by using the detection of antibodies against phenolic glycolipid I. One of the hurdles hampering T-cell-based diagnostic tests is that M. leprae antigens cross-react at the T-cell level with antigens present in other mycobacteria, like M. tuberculosis or M. bovis bacillus Calmette-Guerin (BCG). Using comparative genomics, we previously identified five candidate proteins highly restricted to M. leprae which showed promising features with respect to application in leprosy diagnostics. However, despite the lack of overall sequence homology, the use of recombinant proteins includes the risk of detecting T-cell responses that are cross-reactive with other antigens. To improve the diagnostic potential of these M. leprae sequences, we used 50 synthetic peptides spanning the sequences of all five proteins for the induction of T-cell responses (gamma interferon) in leprosy patients, healthy household contacts (HHC) of leprosy patients, and healthy controls in Brazil, as well as in tuberculosis patients, BCG vaccinees, and healthy subjects from an area of nonendemicity. Using the combined T-cell responses toward four of these peptides, all paucibacillary patients and 13 out of 14 HHC were detected without compromising specificity. The peptides contain HLA binding motifs for various HLA class I and II alleles, thereby meeting an important requirement for the applicability of diagnostic tools in genetically diverse populations. Thus, this study provides the first evidence for the possibility of immunodiagnostics for leprosy based on mixtures of peptides recognized in the context of different HLA alleles.</p>  a1556-679X