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Antifibroblast growth factor receptor 3 antibodies identify a subgroup of patients with sensory neuropathy
  1. Jean-Christophe Antoine1,2,3,4,5,
  2. Nadia Boutahar2,5,6,
  3. François Lassablière7,
  4. Evelyne Reynaud6,
  5. Karine Ferraud1,
  6. Véronique Rogemond4,5,
  7. Stéphane Paul2,4,8,
  8. Jérôme Honnorat4,5,9,
  9. Jean-Philippe Camdessanché1,2,3,4,5
  1. 1Service de Neurologie, CHU de Saint-Etienne, Saint-Etienne, France
  2. 2Université de Saint-Etienne Jean Monnet, Saint-Etienne, France
  3. 3Centre de Référence Maladies Neuromusculaires Rares, CHU de Saint-Etienne, Saint-Etienne, France
  4. 4Centre de Référence Français des Syndromes Neurologiques Paraneoplasiques, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France
  5. 5Lyon Centre de Recherche de Neuroscience INSERM U1028/CNRS UMR 5292, Lyon, France.
  6. 6Laboratoire de Biochimie, CHU de Saint-Etienne, Saint-Etienne, France
  7. 7Department of Neurosciences, Université de Saint-Etienne, Saint-Etienne, France
  8. 8Laboratoire d'Immunologie, CHU de Saint-Etienne, Saint-Etienne, France
  9. 9Université de Lyon—Université Claude Bernard Lyon 1, Lyon, France
  1. Correspondence to Professor Jean-Christophe Antoine, Service de Neurologie, CHU de Saint-Etienne, Saint-Etienne 42055, Cedex 02, France; j.christophe.antoine{at}chu-st-etienne.fr

Abstract

Background Immunological mechanisms are suspected in sensory neuropathy (SN) occurring with systemic autoimmune diseases and in some idiopathic cases, but so far there are no antibodies (Abs) identifying these neuropathies.

Methods In the search for such specific antibodies, serum samples were collected from 106 patients with SN of these 72 fulfilled the diagnosis criteria of sensory neuronopathy (SNN) and 211 control subjects including patients with sensorimotor neuropathies, other neurological diseases (ONDs), systemic autoimmune diseases and healthy blood donors.

Results In the first step, a protein array with 8000 human proteins allowed identification of the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) as a target of Abs in 7/16 SNN and 0/30 controls. In the second step, an ELISA method was used to test the 317 patients and controls for anti-FGFR3 Abs. Abs were detected in 16/106 patients with SN and 1/211 controls (p<0.001). Among the 106 patients with SN, anti-FGFR3 Abs were found in 11/38 patients with autoimmune context, 5/46 with idiopathic neuropathy and 0/22 with neuropathy of other aetiology (p=0.006). The only control patient with anti-FGFR3 Abs had lupus and no recorded neuropathy. Sensitivity, specificity, and positive and negative predictive values of anti-FGFR3 Abs for a diagnosis of idiopathic or dysimmune SN were 19%, 99.6%, 94.1% and 77.3%, respectively. A cell-based assay confirmed serum reactivity against the intracellular domain of FGFR3. The neuropathy in patients with anti-FGF3 Abs was non-length dependent in 87% of patients and fulfilled the criteria of probable SNN in 82%. Trigeminal nerve involvement and pain were frequent features.

Conclusions A anti-FGFR3 Abs identify a subgroup of patients with SN in whom an underlying autoimmune disorder affecting sensory neurons in the dorsal root and trigeminal nerve ganglia is suspected.

  • IMMUNOLOGY
  • NEUROPATHY

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