http://dosequis.colorado.edu/Courses/BrainWeb/papers/MG1.pdf

Myasthenia gravis: a comprehensive review of immune dysregulation and etiological mechanisms.

The end of twentieth century has introduced some changes into T helper (Th) cells division. The identification of the new subpopulation of T helper cells producing IL-17 modified model of Th1–Th2 paradigm and it was named Th17. High abilities to stimulate acute and chronic inflammation made these cells ideal candidate for crucial player in development of autoimmune disorders. Numerous publications based on animal and human models confirmed their pivotal role in pathogenesis of human systemic and organ-specific autoimmune diseases. These findings made Th17 cells and pathways regulating their development and function a good target for therapy. Therapies based on inhibition of Th17-dependent pathways are associated with clinical benefits, but on the other hand are frequently inducing adverse effects. In this review, we attempt to summarize researches focused on the importance of Th17 cells in development of human autoimmune diseases as well as effectiveness of targeting IL-17 and its pathways in pre-clinical and clinical studies.

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The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases

Myasthenia Gravis: Paradox versus paradigm in autoimmunity

No consensus has been reached on the ideal therapeutic algorithm for myasthenia gravis (MG). Most patients with MG require induction therapy with high doses of corticosteroids and maintenance with an immunosuppressant. Severe cases and acute worsening require intravenous immunoglobulin or plasmapheresis before oral immunosuppressants start having an effect. However, biologics are emerging as important therapeutic tools that promise to provide better corticosteroid sparing effects than standard treatments and can even induce remission. In particular, eculizumab, a monoclonal antibody against complement C5, has been approved by the FDA for refractory MG on the basis of a phase III trial. Rituximab, an anti-CD20 monoclonal antibody that depletes peripheral B cells, has also been effective in many large uncontrolled series, although was not in a small phase III trial. Whether the newer anti-CD20 agents ocrelizumab, ofatumumab, obinutuzumab, ublituximab or inebilizumab will be more effective remains unclear. Belimumab, an antibody against the B cell trophic factor BAFF, was ineffective in phase III trials, and efgartigimod, which depletes antibodies, was effective in a phase II study. Some anti-cytokine agents relevant to MG immunopathogenesis also seem promising. Checkpoint inhibitors can trigger MG in some patients, necessitating early intervention. Increased availability of new biologics provides targeted immunotherapies and the opportunities to develop more specific therapies.

Immunotherapy in myasthenia gravis in the era of biologics.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ). Autoantibodies target key molecules at the NMJ, such as the nicotinic acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4), that lead by a range of different pathogenic mechanisms to altered tissue architecture and reduced densities or functionality of AChRs, reduced neuromuscular transmission, and therefore a severe fatigable skeletal muscle weakness. In this review, we give an overview of the history and clinical aspects of MG, with a focus on the structure and function of myasthenic autoantigens at the NMJ and how they are affected by the autoantibodies’ pathogenic mechanisms. Furthermore, we give a short overview of the cells that are implicated in the production of the autoantibodies and briefly discuss diagnostic challenges and treatment strategies.

https://www.mdpi.com/2073-4409/8/7/671/pdf

Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture.

It has been suggested that interleukin-17 (IL-17) plays a crucial role in the development of several autoimmune diseases. However, there are no data about the relationship between myasthenia gravis and IL-17. The aim of this study was to measure the concentration of IL-17 and determine whether levels depend on the severity of MG. Serum IL-17 concentrations were measured in 25 patients. IL-17 concentrations were higher in generalized MG compared with controls and correlated with anti-acetylcholinesterase receptor antibody titers.

Luis Larrad

Papers

Increased serum interleukin‐17 levels in patients with myasthenia gravis