Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase

• Ano de defesa: 2013
• Autor(a) principal: Simon, Marise do Vale
• Orientador(a): Jesus, Amélia Maria Ribeiro de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Sergipe
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• País: BR
• Palavras-chave em Português: Hanseníase; Mycobacterium leprae; Antígenos; Resposta imune
• Palavras-chave em Inglês: Leprosy; Mycobacterium leprae; Antigens; Immune response
• Área do conhecimento CNPq: CNPQ::CIENCIAS DA SAUDE
• Link de acesso: https://ri.ufs.br/handle/riufs/3581

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, intracellular bacterium that causes skin lesions and neurological disorders with sensory loss. The disease constitutes a major public health problem, including Brazil. Many aspects of its immunopathogenesis are still unclear. The inability of growth in culture of bacillus impedes a greater number of experimental studies. The use of recombinant antigens is an important tool for the identification of specific proteins of M. leprae with potential for future use in immunodiagnostic tests in immunoprophylaxis and immunotherapy. The aim of this study was to evaluate the immune response to antigens of M. leprae and M. tuberculosis in protection and pathogenesis of leprosy, using a simple assay with whole blood. Patients with confirmed diagnosis of leprosy using clinical, bacteriological and histological were selected. The operational classification of patients and neurological examination to evaluate the degree of disability were performed. Patients were followed up and some of them have evolved with reactions. The controls household contacts of patients were also selected. The peripheral blood of 55 patients with leprosy, without treatment (39 paucib acillary and 16 multibacillary)and 31 controls were stimulated with antigen crude sonicate of M. leprae (MLCs), purified antigen derived from M. tuberculosis (PPD), 12 recombinant antigens of M. leprae (ML0276, ML2028, ML2055, ML2258, ML2531, ML2629, ML82F, ML2044, ML2380, ML2331, and LID1 PADL) and 2 M. tuberculosis (ID93, ID83). After 24 hours of incubation supernatants were collected and concentrations were determined cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-15, 1L-17A, IL-23, IL-27, IFN-γ, TNF-α and TGF-β, and the chemokine eotaxin, MCP-1 and MIP-1α by Luminex technique. We observed a high concentration of IFN-γ and IL-2 (response Th1) in response to antigens MLCs and PPD in patients with paucibacillary forms and controls in contacts of patients, compared to those with multibacillary forms of the disease. However, no statistically significant differences were observed when analyzing the response to such antigens in patients who subsequently developed with leprosy reactions (n=26) and did not develop leprosy reaction (n = 16) and had the beginning of treatment, degree of disability Physical 0 (n=22) in comparison with the first and second (n=33). Higher concentrations of IFN-γ were detected in patients paucibacillary PADL in response to antigen when compared with patients multibacillary. There was also increased production of MCP-1 in response to ML2531 ID93 and in patients who developed reactions. In conclusion, the production of MCP1 in response to antigens ML 2531 and ID93 can be assayed as a marker of leprosy reactions, antigen MLCs shows a behavior similar to PPD antigen and may be a marker of protective response in leprosy. The PADL antigen may be associated with induction of protective response, suggesting that PADL and MLCs are promising antigens for use in immunotherapy or immunoprophylaxis in leprosy.