Mycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal

Memórias do Instituto Oswaldo Cruz

Kidist Bobosha²  Sheila Tuyet Tang¹  Jolien J Van Der Ploeg-van Schip²  Yonas Bekele¹  Marcia Vsb Martins¹  Ole Lund¹  Kees Lmc Franken²  Saraswoti Khadge¹  Maria Araci De Andrade Pontes¹  Heitor De Sá Gonçalves¹  Jemal Hussien¹  Pratibha Thapa¹  Chhatra B Kunwar¹  Deanna A Hagge¹  Abraham Aseffa¹  Maria Cristina Vidal Pessolani¹  Geraldo Mb Pereira¹  Tom Hm Ottenhoff²  Annemieke Geluk² 

[1] ,University Medical Center Department of Infectious Diseases Leiden,The Netherlands

关键词: M. leprae;    leprosy;    biomarkers;    bioinformatics;    virulence;    peptides;   

DOI  :  10.1590/S0074-02762012000900018

来源: SciELO

【 摘 要 】

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)-γ 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-γ 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.

【 授权许可】

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