{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:00:15Z","timestamp":1782280815127,"version":"3.54.5"},"posted":{"date-parts":[[2025,6,3]]},"group-title":"Neuroscience","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Sensory neuronopathies (SNN) and small fiber neuropathies (SFN) are debilitating disorders associated with neuropathic pain, yet their underlying mechanisms remain poorly understood. Autoantibodies against fibroblast growth factor receptor 3 (FGFR3-Abs) define a subset of patients with consistent reports of neuropathic pain harboring a distinct clinical phenotype characterized by small-fiber and non-length-dependent neuropathy, suggesting dorsal root ganglia (DRG) dysfunction. FGFR3-Abs bind to sensory neurons within dorsal root ganglia (DRG). The target of autoantibodies FGFR3 is expressed at the transcript and protein level in human sensory neurons, suggesting that FGFR3-Abs could find their target in primary afferents. DRG neurons exposed to FGFR3-Abs rapidly acquired a hyperexcitability phenotype which was linked to mechanical hypersensitivity, mirroring patient-reported pain symptoms. CRISPR mediated gene editing of FGFR3 in sensory neuron prevented FGFR3-Abs induced sensitization of sensory neurons and mechanical hypersensitivity. In parallel, Epitope mapping reveals extracellular FGFR3 epitopes essential for antibody-induced sensitization and pain hypersensitivity. Together this work suggests that beyond their role as biomarkers, FGFR3-Abs are pathogenic in small fiber neuropathy by acting directly on DRG neurons. This positions both FGFR3-Abs and FGFR3 signaling as actionable therapeutic targets for modulating sensory neuron excitability and treating autoimmune painful neuropathies.<\/jats:p>","DOI":"10.1101\/2025.06.01.657230","type":"posted-content","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:25:22Z","timestamp":1749014722000},"source":"Crossref","is-referenced-by-count":1,"title":["Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy"],"prefix":"10.64898","author":[{"given":"Lyuba Y","family":"Salih","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA"},{"name":"Institute for Translational Neuroscience, Saint Louis University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas LA","family":"Dumaire","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, 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