Avaliação da resposta imune celular a antígenos recombinantes do Mycobacterium leprae e potencial aplicação para o diagnóstico da hanseníase paucibacilar
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2011-06-30
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Universidade Federal de Goiás
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Title: The evaluation of cellular immune responses to Mycobacterium leprae recombinant antigens and potential application for the diagnosis of paucibacillary leprosy.
Introduction: Leprosy is a chronic and debilitating infectious disease that is characterized by a spectrum of dermato-neurological manifestations associated with different patterns of immune responses. At one end of the spectrum paucibacillary patients (PB) which include tuberculoid (TT) and borderline tuberculoid (BT) patients mount a strong cellular immune response. On the extreme multibacillary (MB) patients including borderline-borderline (BB), borderline-lepromatous (BL) and lepromatous (LL) forms, respond to infection with vigorous antibody production. The diagnosis of leprosy is based on clinical manifestations hampering the early diagnosis before the onset of sequelae. The development laboratory tests applicable for early leprosy diagnosis is considered essential to reduce possible sources of transmission and the number of patients with physical disabilities.
Methods: This work investigated the immune reactivity of a panel of 41 M. leprae (ML) recombinant proteins. The immune reactivity to ML proteins was evaluated by the production of IFNy, measured by ELISA, in the supernatants of 24 hours cultures of heparinized whole blood (whole blood assays/WBA) stimulated with ML antigen (10ug/ml). Study groups were leprosy patients both PB (TT / BT) and MB (BL / LL), newly diagnosed, untreated, classified according to Ridley and Jopling criteria. Household contacts of MB patients (HHC), HIV-1 negative patients with pulmonary tuberculosis (TB) and healthy individuals from the same endemic area (EC) were also investigated. In silico predictions were used to investigate the level of identity of the ML proteins with counterparts in other mycobacteria and to assesse the presence of potential T cell epitopes. For a selected group of immunogenic and specific ML antigens, the profile of 14 cytokines/chemokines induced in WBA was also investigated by Multiplex plataform.
Results and Conclusions: The WBA results identified 11 out of 41 M. leprae recombinant proteins (ML0405, ML2055, ML2331, ML0840, ML1623, ML1556, MLI632, ML1685, ML0276, ML2044, 46f) that were classified as immunogenic and capable of inducing specific cellular immune response. These ML antigens were considered to have potential application for the development of laboratory tests for the diagnosis of PB leprosy. The same pattern of immunoreactivity identified among PB leprosy patients was observed among HHC, while MB leprosy, TB patients and healthy individuals did not respond to these antigens. In silico predictions of immunogenicity and specificity were not confirmed by ex vivo WBA results. The multiplex cytokine study with a selected group of ML antigens showed that besides IFNy, patients with PB leprosy produce other cytokines characteristic of Th1 cells (IL-2 and IL-12). Nevertheless these results that IFNy remained the best immunological marker of cellular immune response of PB patients to recombinant M. leprae proteins. MB leprosy patients secrete mainly Th2 type cytokines such as IL-4 and IL-5 in response to recombinant ML proteins. None of the 14 cytokines/chemokines analyzed in the multiplex was able to distinguish the cellular immune responses of PB patients from the majority of HHC. Although the majority of HHC response identically to PB, we observed that some individuals at greater risk of leprosy infection can mount a Th2 response, similar to MB patients.
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SAMPAIO, L. H. F. Avaliação da resposta imune celular a antígenos recombinantes do Mycobacterium leprae e potencial aplicação para o diagnóstico da hanseníase paucibacilar. 2011. 127 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, 2024.