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Advisor(s)
Abstract(s)
A Miastenia Gravis é a doença autoimune da junção neuromuscular mais comum. Deve-se, maioritariamente, à produção de AC contra os recetores da acetilcolina pós-sinápticos, ou contra a tirosina quinase músculo-específica, que provocam alterações morfológicas e/ou fisiológicas da junção neuromuscular.
Do ponto de vista imunopatogénico, consiste num processo autoimune, dependente de células T, mediado por linfócitos B produtores de auto-AC. O timo parece estar implicado na perda de tolerância aos auto-antigénios, com consequente desenvolvimento da autoimunidade, mas muitos aspetos da patogénese desta doença continuam por decifrar.
Atualmente, várias opções terapêuticas estão disponíveis: timectomia, corticosteroides, imunossupressores, plasmaferese, imunoglobulina intravenosa e imunoadsorção. Contudo, o perfil de efeitos adversos fica aquém do desejado, e nem todos os pacientes respondem ao tratamento atual.
O conhecimento cada vez mais detalhado da fisiopatologia e das bases moleculares da imunopatogénese da miastenia gravis tem permitido o desenvolvimento de tratamentos experimentais cada vez mais específicos. As novas modalidades terapêuticas atuam, nomeadamente, por inibição de certas citocinas, inibição do sistema complemento, manipulação de células dendríticas, indução de tolerância por via oral ou nasal, imunoadsorção antigénio-específica, modulação da acetilcolinesterase e bloqueio dos AChR por AC não patogénicos.
A investigação avança na tentativa de se encontrar uma solução eficaz, segura, com um perfil de efeitos adversos favorável, que corrija especificamente as alterações imunitárias causadoras da doença, sem comprometer o restante sistema imunitário.
Myasthenia Gravis is the most common autoimmune disease of the neuromuscular junction. It is due mostly to the production of antibodies against postsynaptic acetylcholine receptors or against the muscle-specific tyrosine kinase, which cause morphological and/or physiological changes in neuromuscular junction. Immunopathogenically, is a T cell dependent autoimmune process, mediated by B lymphocytes producing self-antibodies. The thymus seems to be implicated in the loss of tolerance to self-antigens, with subsequent development of autoimmunity, but many aspects of the pathogenesis of this disease remain to be deciphered. Currently, several therapeutic options are available: thymectomy, corticosteroids and other immunosuppressants, plasmapheresis and intravenous immunoglobulin, immunoadsorption, and thymectomy. However, the adverse event profile falls short, and not all patients respond to current treatment. The increasingly detailed knowledge of the pathophysiology and molecular basis of the immunopathogenesis of MG has allowed experimental treatments becoming more specific. New therapeutic modalities act in particular by inhibition of certain cytokines, inhibiting the complement system, handling of dendritic cells, induction of oral or nasal tolerance, antigenspecific immunoadsorption, acetylcholinesterase modulation and acetylcholine receptor blocking by non-pathogenic antibodies. The research progresses in an attempt to find an effective, safe treatment, with a favorable adverse event profile, specifically to correct disease-causing immune changes without compromising the rest of the immune system.
Myasthenia Gravis is the most common autoimmune disease of the neuromuscular junction. It is due mostly to the production of antibodies against postsynaptic acetylcholine receptors or against the muscle-specific tyrosine kinase, which cause morphological and/or physiological changes in neuromuscular junction. Immunopathogenically, is a T cell dependent autoimmune process, mediated by B lymphocytes producing self-antibodies. The thymus seems to be implicated in the loss of tolerance to self-antigens, with subsequent development of autoimmunity, but many aspects of the pathogenesis of this disease remain to be deciphered. Currently, several therapeutic options are available: thymectomy, corticosteroids and other immunosuppressants, plasmapheresis and intravenous immunoglobulin, immunoadsorption, and thymectomy. However, the adverse event profile falls short, and not all patients respond to current treatment. The increasingly detailed knowledge of the pathophysiology and molecular basis of the immunopathogenesis of MG has allowed experimental treatments becoming more specific. New therapeutic modalities act in particular by inhibition of certain cytokines, inhibiting the complement system, handling of dendritic cells, induction of oral or nasal tolerance, antigenspecific immunoadsorption, acetylcholinesterase modulation and acetylcholine receptor blocking by non-pathogenic antibodies. The research progresses in an attempt to find an effective, safe treatment, with a favorable adverse event profile, specifically to correct disease-causing immune changes without compromising the rest of the immune system.
Description
Keywords
Miastenia gravis Miastenia gravis - Fisiopatologia Miastenia gravis - Autoimunidade Miastenia gravis - Tratamento Miastenia gravis - Aspectos neuromusculares
Citation
Publisher
Universidade da Beira Interior