Myasthenie.com

Eur J Neurol. 2023 Feb 8. doi: 10.1111/ene.15730. Online ahead of print.

ABSTRACT

BACKGROUND: Complement component 5 (C5)-targeting therapies are clinically beneficial in patients with acetylcholine receptor antibody+ (AChR-Ab+ ) generalized Myasthenia Gravis (MG). That clearly implicates antibody-mediated complement activation in MG pathogenesis. Here, we profiled classical and alternative complement pathways in patients from different MG subgroups.

METHODS: In a case-control study, we simultaneously quantified concentrations of C3a, C5a, and sC5b9, indicating general activation of the complement system, whether via the classical and lectin pathways (C4a) or alternative pathway (factors Ba and Bb) in MG patients with AChR or muscle-specific kinase antibodies (MuSK-Ab) or seronegative MG compared to healthy donors.

RESULTS: Treatment naïve patients with AChR-Ab+ MG showed substantially increased plasma levels of cleaved complement components, indicating activation of the classical and alternative as well as the terminal complement pathways. These increases were still present in a validation cohort of AChR-Ab+ patients under standard immunosuppressive therapies; notably, they were not evident in patients with MuSK-Ab or seronegative MG. Neither clinical severity parameters (at the time of sampling or one year later) nor anti-AChR titers correlated significantly with activated complement levels.

CONCLUSIONS: Markers indicative of complement activation are prominently increased in patients with AChR-Ab MG despite standard immunosuppressive therapies. Complement inhibition proximal to C5 cleavage should be explored for its potential therapeutic benefits in AChR-Ab+ MG.

PMID:36752022 | DOI:10.1111/ene.15730


Source: https://pubmed.ncbi.nlm.nih.gov/3675202 ... t6+86293ac