Gephyrin Neurological Autoimmunity
Gephyrin is a postsynaptic scaffold protein essential for inhibitory neurotransmission. Gephyrin-immunoglobulin G (IgG) was reported, decades ago, in a single case of paraneoplastic stiff-person-like syndrome, but its broader clinical relevance remains unknown. While investigating unclassified synaptic IgGs mimicking amphiphysin-IgG, we identified gephyrin-IgG in 3 patients using human protein microarray. Gephyrin specificity was confirmed using confocal tissue-based immunofluorescence assay, cell-based assay, and Western blot. The 3 patients, all female, had: encephalitis (2) and myeloneuropathy and breast cancer (1). All had inflammatory cerebrospinal fluid and abnormal magnetic resonance imaging, and improved following immunotherapy. Gephyrin-IgG is associated with a treatable autoimmune neurological disease, sometimes paraneoplastic. ANN NEUROL 2026.
Authors
- N Arenson
- Αναστασία Ζεκερίδου (ORCID: https://orcid.org/0000-0002-1960-9065)
- Friederike A. Arlt (ORCID: https://orcid.org/0000-0002-0112-8685)
- Andrew B. McKeon (ORCID: https://orcid.org/0000-0001-6856-8143)
- Connie E. Lesnick (ORCID: https://orcid.org/0009-0008-2812-1214)
- Sean Joseph Pittock (ORCID: https://orcid.org/0000-0002-6140-5584)
- Michael Lane (ORCID: https://orcid.org/0000-0001-6517-9206)
- Divyanshu Dubey (ORCID: https://orcid.org/0000-0002-4302-4075)
- Maria Chiara Pantuliano (ORCID: https://orcid.org/0009-0005-5681-9116)
- Irena Dujmovic Basuroski
- John R. Mills
Institutions
- University of North Carolina at Chapel Hill (US)
- Peninsula College (US)
- Università Campus Bio-Medico (IT)
- Oregon Health & Science University (US)
- Mayo Clinic in Arizona (US)
- Campus Bio Medico University Hospital (IT)
Publication Details
- Journal
- Annals of Neurology
- Published
- 2026-06-17
- DOI
- https://doi.org/10.1002/ana.78278
- Primary Topic
- Autoimmune Neurological Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00