PMID- 23283462 OWN - NLM STAT- MEDLINE DCOM- 20131119 LR - 20190606 IS - 1678-8060 (Electronic) IS - 0074-0276 (Linking) VI - 107 Suppl 1 DP - 2012 Dec TI - Mycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal. PG - 112-23 LID - S0074-02762012000900018 [pii] AB - Silent transmission of Mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. Therefore, the development of tools for the early diagnosis of M. leprae infection should be emphasised in leprosy research. As part of the continuing effort to identify antigens that have diagnostic potential, unique M. leprae peptides derived from predicted virulence-associated proteins (group IV.A) were identified using advanced genome pattern programs and bioinformatics. Based on human leukocyte antigen (HLA)-binding motifs, we selected 21 peptides that were predicted to be promiscuous HLA-class I T-cell epitopes and eight peptides that were predicted to be HLA-class II restricted T-cell epitopes for field-testing in Brazil, Ethiopia and Nepal. High levels of interferon (IFN)-gamma were induced when peripheral blood mononuclear cells (PBMCs) from tuberculoid/borderline tuberculoid leprosy patients located in Brazil and Ethiopia were stimulated with the ML2055 p35 peptide. PBMCs that were isolated from healthy endemic controls living in areas with high leprosy prevalence (EChigh) in Ethiopia also responded to the ML2055 p35 peptide. The Brazilian EChigh group recognised the ML1358 p20 and ML1358 p24 peptides. None of the peptides were recognised by PBMCs from healthy controls living in non-endemic region. In Nepal, mixtures of these peptides induced the production of IFN-gamma by the PBMCs of leprosy patients and EChigh. Therefore, the M. leprae virulence-associated peptides identified in this study may be useful for identifying exposure to M. leprae in population with differing HLA polymorphisms. FAU - Bobosha, Kidist AU - Bobosha K AD - Department of Infectious Diseases, University Medical Center, Leiden, The Netherlands. FAU - Tang, Sheila Tuyet AU - Tang ST FAU - van der Ploeg-van Schip, Jolien J AU - van der Ploeg-van Schip JJ FAU - Bekele, Yonas AU - Bekele Y FAU - Martins, Marcia V S B AU - Martins MV FAU - Lund, Ole AU - Lund O FAU - Franken, Kees L M C AU - Franken KL FAU - Khadge, Saraswoti AU - Khadge S FAU - Pontes, Maria Araci de Andrade AU - Pontes MA FAU - Goncalves, Heitor de Sa AU - Goncalves Hde S FAU - Hussien, Jemal AU - Hussien J FAU - Thapa, Pratibha AU - Thapa P FAU - Kunwar, Chhatra B AU - Kunwar CB FAU - Hagge, Deanna A AU - Hagge DA FAU - Aseffa, Abraham AU - Aseffa A FAU - Pessolani, Maria Cristina Vidal AU - Pessolani MC FAU - Pereira, Geraldo M B AU - Pereira GM FAU - Ottenhoff, Tom H M AU - Ottenhoff TH FAU - Geluk, Annemieke AU - Geluk A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Brazil TA - Mem Inst Oswaldo Cruz JT - Memorias do Instituto Oswaldo Cruz JID - 7502619 RN - 0 (Bacterial Proteins) RN - 0 (Cytokines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Proteins) SB - IM MH - Bacterial Proteins/immunology MH - Brazil MH - Computational Biology MH - Cytokines/*immunology MH - Epitope Mapping MH - Epitopes, T-Lymphocyte/*immunology MH - Ethiopia MH - Humans MH - Mycobacterium leprae/immunology/isolation & purification/*pathogenicity/virology MH - Nepal MH - Peptide Fragments/immunology MH - Recombinant Proteins/immunology MH - Virulence/*immunology EDAT- 2013/01/11 06:00 MHDA- 2013/11/20 06:00 CRDT- 2013/01/04 06:00 PHST- 2012/03/08 00:00 [received] PHST- 2012/07/03 00:00 [accepted] PHST- 2013/01/04 06:00 [entrez] PHST- 2013/01/11 06:00 [pubmed] PHST- 2013/11/20 06:00 [medline] AID - S0074-02762012000900018 [pii] AID - 10.1590/s0074-02762012000900018 [doi] PST - ppublish SO - Mem Inst Oswaldo Cruz. 2012 Dec;107 Suppl 1:112-23. doi: 10.1590/s0074-02762012000900018.