Evidence map›Paper›PMID 42308456›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2026

Functional Profiling of Acetylcholine Receptor Antibodies Informs Therapeutic Outcome of FcRn Inhibitor Therapy in Myasthenia Gravis.

Veronica Morcone, Jacopo Morroni, Giuseppe Valenzano, Sofia Marini, Silvia Falso, Martina Marini, Federico Habetswallner, Giorgia Farì, Cinzia Carrozza, Raffaele Iorio

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Article in Neurology(R) neuroimmunology & neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Veronica MorconeDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0009-0007-1388-1862
Jacopo MorroniNeurology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; and.
Giuseppe ValenzanoDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0009-0000-5657-3033
Sofia MariniDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0009-0002-4982-1662
Silvia FalsoDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0000-0002-6264-5299
Martina MariniDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0009-0007-5730-6173
Federico HabetswallnerDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0009-0003-0317-1606
Giorgia FarìChemistry, Biochemistry and Molecular Biology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.ORCID 0000-0002-0946-0973
Cinzia CarrozzaChemistry, Biochemistry and Molecular Biology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Raffaele IorioDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID 0000-0002-6270-0956

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesMyasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction most commonly associated with acetylcholine receptor (AChR) antibodies (AChR-Abs), detected in up to 80% of patients. The emergence of targeted therapies, such as neonatal Fc receptor (FcRn) inhibitors, highlights the need for standardized functional assays capable of dissecting AChR-Ab pathogenic mechanisms. By selectively reducing circulating IgG through FcRn blockade, these agents differ fundamentally from conventional immunosuppressants, emphasizing the need to characterize antibody-mediated AChR dysfunction and complement activation as potential markers of therapeutic response. However, current functional assays often rely on transiently transfected or heterogeneous cell systems, limiting reproducibility and scalability. A stably transfected human cell line expressing physiologically clustered adult AChRs could fill this methodological gap and enable standardized, quantitative evaluation of antibody effector functions.

methodsWe generated a stable rhabdomyosarcoma (RD) cell line expressing clustered human adult AChRs (hAChR-RDcl) using the

resultsThe hAChR-RDcl cell line showed stable transcription and surface expression of adult AChR subunits, confirmed by RT-qPCR, α-bungarotoxin binding, and antibody-specific reactivity (mAb637 and patient serum samples). Baseline functional assays identified blocking antibodies in 15 of 30 (50%), internalizing antibodies in 20 of 30 (66.7%), and complement-activating antibodies in 14 of 30 (46.6%) samples. After efgartigimod treatment, all 3 antibody-mediated mechanisms were significantly reduced. Patients with persistent complement activity after treatment experienced more severe symptoms (higher QMG scores) compared with those showing other antibody-mediated pathogenetic mechanisms or complete suppression of antibody effector functions. DISCUSSION: The hAChR-RDcl cell line represents a reliable and scalable platform for standardized functional profiling of AChR-Abs. Functional characterization of AChR-Abs provides a translational approach to monitor therapeutic responses and elucidate the mechanisms underlying FcRn inhibitor efficacy in MG.

Indexed as

AutoantibodiesHistocompatibility Antigens Class IMyasthenia GravisReceptors, CholinergicReceptors, FcAdultCell Line, TumorFemaleHumansAutoantibodiesFc receptor, neonatalHistocompatibility Antigens Class IReceptors, CholinergicReceptors, Fc

Identifiers

PMID42308456
PMCPMC13276697

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