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Review
. 2025 May 19;14(10):739.
doi: 10.3390/cells14100739.

The Role of Complement in the Pathogenesis and Treatment of Myasthenia Gravis

Armando Martinez Salazar  1 , Sepideh Mokhtari  1   2 , Edwin Peguero  1   2 , Muhammad Jaffer  1   2
Affiliations
Review

The Role of Complement in the Pathogenesis and Treatment of Myasthenia Gravis

Armando Martinez Salazar et al. Cells. .

Abstract

Myasthenia gravis is an antibody-mediated autoimmune condition characterized by defects in cholinergic transmission at the neuromuscular junction. In AchR antibody-positive patients, complement activation plays a prominent role in the disease process, which appears to be mediated by the activation of the membrane attack complex. Since IgG4 is not a good complement activator, the role of complement in MuSK antibody-positive myasthenia gravis patients is negligible. Experimental animal models of myasthenia gravis have shown promise with the antagonism of different elements of the complement cascade, with positive clinical outcomes. This has led to the development of the first C5 inhibitors approved for myasthenia gravis with AchR antibodies: eculizumab, ravulizumab, and zilucoplan. Other clinical trials are currently in progress, investigating the potential therapeutic role of other targets, including the Factor B inhibition or hepatic synthesis of the C5 protein. Other proposed potential targets that have not yet been clinically tested are also discussed in this review article.

Keywords: acetylcholine receptor antibodies; cemdisiran; complement; eculizumab; gefurulimab; myasthenia gravis; pozelimab; ravulizumab; vemircopan; zilucoplan.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Summary of the complement cascade and its functions. Created in Biorender. Jaffer, M. (2025) https://BioRender.com/illustrations/67b87bf898d27ce5f197797a?slideId=37f77c61-0bc1-4db8-b97b-6e32c4ddd66c.
Figure 2
Figure 2
Complement-mediated membrane attack complex formation at the neuromuscular junction. Created in Biorender. Jaffer, M. (2025) https://BioRender.com/illustrations/67b8ca00cd23a08cdcf9decf?slideId=01ed1598-d900-4eff-aba0-8e4687b49cfd.
See this image and copyright information in PMC

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