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

J Neuroimmunol. 2021 Dec 15:361:577757. doi: 10.1016/j.jneuroim.2021.577757. Epub 2021 Oct 30.

Abstract

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.

Keywords: Anti-FGFR3 autoantibody; Epitope mapping; Immune-mediated neuropathy; Peripheral neuropathy; Phosphorylation; Sensory neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantigens / chemistry
  • Autoantigens / immunology*
  • Autoimmune Diseases of the Nervous System / immunology*
  • Epitopes / immunology*
  • Female
  • Ganglia, Spinal / immunology
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / immunology*
  • Phosphorylation
  • Protein Domains
  • Protein Processing, Post-Translational
  • Receptor, Fibroblast Growth Factor, Type 3 / chemistry
  • Receptor, Fibroblast Growth Factor, Type 3 / immunology*
  • Sensation Disorders / immunology*
  • Sensory Receptor Cells / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Epitopes
  • Nerve Tissue Proteins
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3