Anti-FGFR3 antibody epitopes are functional sites and correlate with the neuropathy pattern

Antibodies against FGFR3 define a subgroup of sensory neuropathy (SN). The aim of this study was to identify the epitope(s) of anti-FGFR3 autoantibodies and potential epitope-dependent clinical subtypes. Using SPOT methodology, five specific candidate epitopes, three in the juxtamembrane domain (JMD) and two in the tyrosine kinase domain (TKD), were screened with 68 anti-FGFR3-positive patients and 35 healthy controls. The identified epitopes cover 6/15 functionally relevant sites of the protein. Four patients reacted with the JMD and 11 with the TKD, partly even in a phosphorylation-state dependent manner. The epitope could not be identified in the others. Patients with antibodies recognizing TKD exhibited a more severe clinical and electrophysiological impairment than others. [Display omitted] •Anti-FGFR3 antibodies are associated with sensory neurons disorders.•In 22% of patients the epitope is located in the FGFR3 juxta-membrane and tyrosine kinase domains (TKD).•Several epitopes are recognized depending on their phosphorylation state.•The identified epitopes cover functionally relevant sites of FGFR3.•Patients reacting with the FGFR3 TKD have more severe sensory neuropathy than others.