FGFR3 Antibodies in Neuropathy. What to do with them? (P1.463)

Objective: To describe the variability of fibroblast growth factor receptor 3 (FGFR3) antibody titers in a series of patients with neuropathy. Background: FGFR3 antibodies have been reported in sensory neuropathy, in the context of autoimmune diseases, using ELISA test as screening method and cell-based assay as confirmatory test. Currently available commercial testing only utilizes ELISA testing. Design/Methods: We performed a retrospective chart review of neuropathy patients with initial positive FGFR3 levels. All FGFR3 antibody testing was performed at the same commercial laboratory. Results: We report five patients with positive FGFR3 antibodies, three women and two men, aged 44 – 74 years. Repeat testing revealed absent antibody titers in two and a significant drop in one patient. High titers (18,000 – 65,000) were present in 4 patients, and low titers in one patient who had no repeat testing. Symptom onset was sudden in 3 and slowly progressive in 2 patients. Four patients reported neuropathic pain; one reported autonomic symptoms. Clinical examination ranged from normal large fiber sensation to mild/moderate predominantly sensory neuropathy; one exhibited sensory ataxia. Four patients showed mild worsening on follow-up examination. NIS-LL scores ranged from 2 to 28. Additional antibodies included: trisulfated disaccharide IdoA2S-GlcNS-6S in two patients, and anti-histone H3 antibodies in 1 patient. One patient had paraproteinemia. Concomitant diseases include polycythemia vera, sarcoidosis, and diabetes mellitus. Electrodiagnostic testing revealed: normal large fiber function (2), severe demyelinating polyneuropathy with axonal features (1). mild/moderate sensorimotor peripheral neuropathy with mixed features (2). No immunotherapy was employed between visits or antibody testing. Conclusions: Our case series highlights the variability and inconsistency in FGFR3 antibody titers by ELISA testing methodology. These antibody titers should be interpreted with caution and clinicians should consider repeat testing or confirmatory testing prior to initiating immunotherapy. Disclosure: Dr. Samara has nothing to disclose. Dr. Sampson has nothing to disclose. Dr. Muppidi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Lundbeck.