Inflammation Could Prove Meaningful Target in Myasthenia Gravis

The article suggests the inflammatory components of myasthenia gravis have been underexplored in the effort to develop new therapies.

New therapeutic strategies to treat myasthenia gravis (MG) ought to exploit the apparent association between the disease and inflammation, according to a new review published in Frontiers in Immunology.

This analysis argues that a better understanding of the role of inflammation could lead to the development of better therapies or of combination therapies that target both the autoantibody and inflammatory components of MG.

MG is a chronic autoimmune disease in which autoantibodies bind to acetylcholine receptors (AChRs), thereby reducing their functionality and leading to symptoms like muscle weakness and fatigue. However, the study author noted that inflammation is also a common feature of the disease.

She said mediators of inflammation, such as cytokines and chemokines, are released by inflammatory monocytes and macrophages in the postsynaptic neuromuscular junction (NMJ) or thymic tissue, and then into peripheral circulation.

“Subsequently, AChR-specific T-helper cells infiltrate the NMJ or thymic microenvironment and interact with B cells to induce its autoimmune activation,” wrote Ruksana Huda, PhD, University of Texas Medical Branch.

She also noted that a dysregulated inflammatory response has been linked with other autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus, but that existing therapies for MG, such as monoclonal antibodies (mAbs), have variable degrees of effectiveness, and some patients are refractory to such therapies.

“Therefore, in addition to the mAb-based therapies against conventional immune cell–associated biomarkers, there is also a need for adjunct therapies directed to new, precise, and reliable targets for inflammation that can ensure fulfilling the current gap in targeted therapy,” she wrote.

Huda discussed ways in which inflammation and immune dysregulation play roles in the development of the autoimmune disease, and then outlined some of the key inflammatory mediators.

Turning toward therapeutic options. She noted that tocilizumab has shown effectiveness in patients with MG who are refractory to rituximab. Tocilizumab is a recombinant humanized mAb targeting–membrane bound or soluble interleukin-6 (IL-6) receptor. However, she said other inflammatory mediator–targeting therapies have had mixed results or have not been tested in MG.

“For example, etanercept (a tumor necrosis factor-α antagonist decoy receptor) was beneficial for patients with low plasma levels of IL-6 and interferon γ, but it exacerbated MG in a patient with RA and also reactivated tuberculosis,” she wrote. She said other anti–IL-6 antibodies were not tested in patients in MG.

Huda said 2 humanized mAbs targeting interferon-α, rontalizumab and anifrolumab, “produced contradictory results in MG or [a] mice model of MG, and therefore no clinical trial in MG was conducted.”

She said novel treatments are also being investigated for MG.

Huda concluded by arguing that there are sufficient basic and clinical research data to link inflammation with MG.

“Utilizing new technologies and highly efficient tools for research and data collection, it is possible to conduct a more comprehensive mechanistic study about the role of inflammation in autoimmune development or modulation of the autoimmune response in preclinical models of MG and MG,” she wrote.

She said those strategies could help design better therapies for MG and that combination therapies that address both the autoantibody and inflammatory components of the disease could prove beneficial.


Huda R. Inflammation and autoimmune myasthenia gravis. Front Immunol. Published online January 30, 2023. doi:10.3389/fimmu.2023.1110499

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