ArticleEBioMedicine2026
Complement C3 inhibition restores myasthenia gravis AChR antibody-mediated muscle pathophysiology.
Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Complement C3 is associated with cancer-induced frailty: genetic and clinical evidence.Frontiers in nutrition · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the autoimmune disorder myasthenia gravis (MG), the nicotinic acetylcholine receptors (nAChRs) are the primary targets of pathogenic antibodies. While MG mechanisms have been extensively studied in animal models, functional insights into how antibody binding disrupts nAChR-dependent calcium signaling and the effects of complement inhibition in human muscle cells remain limited.
methodsWe used real-time live-cell calcium imaging to assess the effects of cholinergic stimulation or inhibition on human muscle cells with pharmacological agents, sera from patients with acetylcholine receptor antibody seropositive (AChR+) MG, purified recombinant antibodies targeting α- and β-subunits, and a complement C3 inhibitor. Transcriptional changes in nAChR subunits, muscle markers, voltage-gated calcium channels (VGCCs), and complement-related genes were analysed by RT-qPCR. Immunocytochemistry and quantitative image analysis were performed to assess nAChR distribution and membrane attack complex (MAC) deposition.
findingsCholinergic stimulation of human muscle cells activated nAChRs, resulting in membrane depolarisation, which in turn led to VGCC opening and calcium transients. MG-associated pathogenic antibodies, particularly those present in sera from patients with AChR + MG and pure recombinant AChR α-subunit-specific monoclonal antibody (mAb), but not β-subunit-specific, abolished choline-induced calcium responses in myotubes. α-subunit-specific mAb also induced transcriptional upregulation of nAChR subunits, muscle structural proteins, and complement components, and were associated with nAChR loss and MAC formation. Importantly, pharmacological inhibition of C3 activation restored calcium signaling, preserved nAChR distribution, and reduced MAC formation induced by α-subunit-specific mAb, implicating complement activation as a key driver of pathogenic effects.
interpretationThese findings indicate that targeting the α-subunit impairs nAChR-dependent calcium signaling and can induce complement activation. Disrupted signaling and reduced nAChR levels were effectively restored by C3 inhibition, which blocks multiple downstream pathways; thus, terminal complement activation leading to MAC formation is a suggested, but it may not be the only mechanism. Overall, the results highlight C3 as a promising upstream therapeutic target and support combining subunit-specific interventions with proximal complement blockade in MG.
fundingThis work was supported by Familjen Erling-Perssons Stiftelse (grant # 2022_0030 to ARP), the Myasthenia Gravis Foundation of America, and the Swedish Research Council (grant # 2025-02779 to ARP). MLF part of the work was supported by a grant from the Deutsche Gesellschaft für Muskelkranke e.V. (DGM).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.