Resposta imune a antígenos do Mycobacterium leprae na forma neural pura de hanseníase

• Autor(a) principal: Figueiredo, Vilma de
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/8634
• topic: Leprosy; Pure neural leprosy; Mycobacterium leprae; Cellular immunity; Neuropathy; Unfractionated blood; Paucibacillary; Biomarkers; Peptides; Hanseníase; Neural pura; M. leprae; Resposta imune; Antígeno; Neuropatia; Sangue não fracionado; Paucibacilar; Biomarcadores; Peptídeos; Hanseníase; Neuropatia; Mycobacterium leprae; Resposta imune; Hanseníase Paucibacilar; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA

Analysis of the genome suggests that Mycobacterium leprae emerged in the Pleistocene about 100,000 years ago, and its spread followed the migration route of the first humans, with which this pathogen spread throughout the world. This bacillus is the etiological agent of leprosy, a public health problem in Brazil, and in several other countries, where leprosy is an endemic disease. It is an obligate intracellular pathogen that induces injury to the peripheral nerves and skin. The detection of bacillus in the skin lesion and the neuropathy allow the diagnosis of the disease. Peripheral neuropathy with no skin lesion is seen in pure neural leprosy (PNL). Understanding the pathogen-specific immune response is critical for the development of tools that will allow the early diagnosis of PNL and other forms of leprosy. Early diagnosis of the disease is necessary to reduce the frequent disabilities in leprosy and the transmission of this infection. The general objective of this investigation is to investigate whether the levels of cytokines induced by M. leprae-specific antigens may be a diagnostic tool for leprosy, especially to exclude the leprosy hypothesis in patients with peripheral neuropathies. Plasma and supernatant samples from 60 donors (healthy controls, patients with multibacillary leprosy, paucibacillary and pure neural leprosy, and patients with other peripheral neuropathies) were analyzed by multiplex assay following stimulation with M. leprae-specific antigens. Patients with PNL responded to control and M. leprae-specific stimuli. Responses were evaluated both in peripheral blood mononuclear cells and in non-fractionated blood. Elevated levels of proinflammatory cytokines and chemokines were induced in response to M. leprae antigens in the healthy control (ABE) group and these levels gradually decreased as they approached the more severe form of the disease (LL). The results obtained from serum samples from HNP patients show that these two markers would not have great diagnostic utility in the form of leprosy. However, in patients with HNP with anti-PGL-I and anti-LID-1 positivity, perhaps the pre and post-treatment serology by multidrug therapy may be an element of evaluation of therapeutic response. The PNL group demonstrated a response comparable to the tuberculoid forms of leprosy. IFN-γ, IL-17, and several other biomarkers of T cell functional activation induced by stimulation with specific antigens of M. leprae, showed progressive reduction when exposed individuals without leprosy were compared with patients. These biomarkers were detected at lower levels in patients with multibacillary forms of leprosy. Principal component analysis of the cytokine levels induced by the ML1419c protein and synthetic M. leprae-specific peptides allowed separation of leprosy patients including PNL, from healthy subjects and patients with non-leprosy peripheral neuropathies. Inclusion of new parameters, perhaps associated with peripheral neural damage or M. leprae infection of Schwann cells, are additional elements that may increase the accuracy of discrimination of PNL from other non-leprosy peripheral neuropathies.