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Neuro-inflammation
Original research
Clinical characterisation of sensory neuropathy with anti-FGFR3 autoantibodies
  1. Yannick Tholance1,2,
  2. Christian Peter Moritz2,
  3. Carole Rosier2,3,
  4. Karine Ferraud3,
  5. François Lassablière2,
  6. Evelyne Reynaud-Federspiel2,
  7. Marcondes C França Jr4,
  8. Alberto R M Martinez4,
  9. Jean-Philippe Camdessanché2,3,
  10. Jean-Christophe Antoine2,3
  11. anti-FGFR3 antibody Study Group
    1. 1 Laboratory of Biochemistry, CHU Saint-Etienne, Saint-Etienne, France
    2. 2 Synaptopathies et autoanticorps (synatac), Institut Neuromyogène, Saint-Priest-en-Jarez, France
    3. 3 Department of Neurology, CHU Saint-Etienne, Saint-Etienne, France
    4. 4 Department of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
    1. Correspondence to Dr Yannick Tholance, Laboratory of Biochemistry, CHU Saint-Etienne, Saint-Etienne 42055, France; yannick-tholance{at}hotmail.fr

    Abstract

    Objective Sensory neuropathies (SNs) are often classified as idiopathic even if immunological mechanisms can be suspected. Antibodies against the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) possibly identify a subgroup of SN affecting mostly the dorsal root ganglion (DRG). The aim of this study was to identify the frequency of anti-FGFR3 antibodies and the associated clinical pattern in a large cohort of patients with SN.

    Methods A prospective, multicentric, European and Brazilian study included adults with pure SN. Serum anti-FGRF3 antibodies were analysed by ELISA. Detailed clinical and paraclinical data were collected for each anti-FGFR3-positive patient and as control for anti-FGFR3-negative patients from the same centres (‘center-matched’).

    Results Sixty-five patients out of 426 (15%) had anti-FGFR3 antibodies, which were the only identified autoimmune markers in 43 patients (66%). The neuropathy was non-length dependent in 89% and classified as sensory neuronopathy in 64%, non-length-dependent small fibre neuropathy in 17% and other neuropathy in 19%. Specific clinical features occurred after 5–6 years of evolution including frequent paresthesia, predominant clinical and electrophysiological involvement of the lower limbs, and a less frequent mixed large and small fibre involvement. Brazilians had a higher frequency of anti-FGFR3 antibodies than Europeans (36% vs 13%, p<0.001), and a more frequent asymmetrical distribution of symptoms (OR 169, 95% CI 3.4 to 8424).

    Conclusions Anti-FGFR3 antibodies occur in a subgroup of SN probably predominantly affecting the DRG. Differences between Europeans and Brazilians could suggest involvement of genetic or environmental factors.

    • anti-FGFR3 autoantibodies
    • autoimmune diseases
    • fibroblast growth factor receptor 3 (FGFR3)
    • sensory neuronopathies
    • sensory neuropathies

    https://doi.org/10.1136/jnnp-2019-321849

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      Footnotes

      • Collaborators Collaborators anti-FGFR3 antibody Study Group: David Adams, MD, PhD, Cécile Cauquil, MD (FILNEMUS, Department of Neurology, Kremlin Bicêtre hospital, AP-HP, University of Paris-Sud, Bicêtre, France, site investigator); Shahram Attarian, MD, PhD, Emilien Delmont, MD (Reference Center for neuromuscular disorders and ALS, University Hospital La Timone, Aix-Marseille University, Marseille, France, site investigator); Genevieve Blanchet-Fourcade, MD (Department of Neurology, Hospital Center of Narbonne, Narbonne, France, site investigator); Céline Callias, MD (Department of Neurology, Central institute of hospitals (ICH), Valais Hospital, Sion, Switzerland, site investigator); Julien Cassereau, MD (Department of Neurology, ALS Center, University Hospital of Angers, Angers, France, site investigator); Ariane Choumert, MD (Department of Neurology, University hospital of the Reunion, SaintPierre, France, site investigator); Pierre Clavelou, MD, PhD (Department of Neurology, University hospital of Clermont-Ferrand, Clermont-Ferrand, France, site investigator); Alain Créange, MD, PhD (Department of Neurology, CHU Créteil, Henri Mondor University Hospital, Créteil, France, site investigator); Gabriella Di Virgilio, MD (Department of Neurology, RivieraChablais Hospital, Vevey, Switzerland, site investigator); Andoni Echaniz-Laguna, MD (Department of Neurology, University hospital of Strasbourg, Strasbourg, France, site investigator); Benoit Faucher, MD (Department of Multidisciplinary Medicine, Toulon-La Seyne-sur-Mer Intercommunal Hospital Center, Toulon, France, site investigator); Ian Galea, MD (Wessex Neurosciences Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK, site investigator); Steeve Genestet, MD (Department of Neurological Functional Explorations, University Hospital of Brest, Brest, France, site investigator); Antoine Guéguen, MD (Department of Neurology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France, site investigator); Ioana M Ion, MD (Department of Neurology, University Hospital of Nîmes, Nîmes, France, site investigator); Raul Juntas-Morales, MD, Guillaume Taieb, MD (Department of Neurology, University hospital of Montpellier, Montpellier, France, site investigator); Thierry Kuntzer, MD, PhD (Department of Neurology, Lausanne University Hospital CHUV, Lausanne, Switzerland, site investigator); Emmeline Lagrange, MD (Department of Neurology, University Hospital of Grenoble, Grenoble, France, site investigator); Jean-Marc Léger, MD, PhD, Tanya Stojkovic, MD, PhD (National Referral Center for Neuromuscular Diseases, University Hospital Pitié-Salpétrière, Paris, France, site investigator); Maud Lepetit, MD (Department of Neurology, Cornouailles Hospital Center, Quimper, France, site investigator); Laurent Magy, MD, PhD (Department of Neurology, Reference Center for Rare Peripheral Neuropathies, University Hospital of Limoges, Limoges, France, site investigator); Julie Mas, MD (Department of Neurology, St. Jean Hospital, Perpignan, France, site investigator); Maud Michaud, MD (Department of Neurology, University Hospital of Nancy, Nancy, France, site investigator); Capucine Mouthon-Reignier, MD (Department of Neurology, Sud francilien Hospital Center, Corbeil-Essonnes, France, site investigator); Jean-Philippe Neau, MD, PhD (Department of Neurology, Poitiers University Hospital, Poitiers, France, site investigator); Canan Ozsancak, MD (Department of Neurology, Regional Hospital Center of Orléans, Orléans, France, site investigator); Yann Péréon, MD, PhD (Center for Neuromuscular Diseases, Hôtel-Dieu Hospital, Nantes, France, site investigator); Paul Perrotte, MD (Department of Neurology, Hospital Center of Le Havre, Le Havre, France, site investigator); Angela Puma, MD (Peripheral Nervous System, Muscle and ALS Department, University of Nice and Côte d'Azur (UCA), Nice, France, site investigator); Yusuf A Rajabally, MD, PhD (Regional Neuromuscular Clinic, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham, UK, site investigator); Simon Rinaldi, MD, PhD (Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital Oxford, Oxford, UK, site investigator); Violaine Rouaud, MD (Department of Neurology, Bretagne-Atlantique Hospital Center, Vannes, France, site investigator); Guilhem Sole, MD (Department of Neurology, University hospital of Bordeaux, Bordeaux, France, site investigator); Céline Tard, MD (Department of Neurology and Movement Disorders, Lille University Medical Center, Lille, France, site investigator); Anne-Evelyne Vallet, MD (Department of Neurology, Hospital Center of Vienne, Vienne, France, site investigator) and Christophe Vial, MD (Neuromuscular Reference Center, Hospices Civils de Lyon, Bron, site investigator).

      • Contributors YT and J-CA had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: J-PC and J-CA. Acquisition, analysis and interpretation of data: all authors. Drafting the manuscript: YT, CPM, J-PC and J-CA. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: YT and J-CA.

      • Funding This study was supported by University hospital of Saint-Etienne (NCT02539329). CPM was funded by the German Research Foundation (DFG; MO 3240/1-1:1) during the study. MCFJ has a research grant on SNN funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/01766-7). ARMM is supported by PhD scholarship from FAPESP (2013/26410-0).

      • Competing interests YT reports personal fees from The Binding Site and Alexion, outside of the submitted work. CPM received travel grants from CSL Behring (France), outside of the submitted work. J-PC reports personal fees for lectures, consulting, writing of articles, or training courses from Akcea, Alnylam, Biogen, CSL Behring, Genzyme, Laboratoire Français des Biotechnologies (LFB), Merck, Novartis, Pfizer, Pharmalliance, Teva, Editions Scientifiques L&C, Edimark, Expression Santé, Natus, Scien, SNF-Floerger, outside of the submitted work. J-CA received honoraria for scientific counseling from Pfizer and from a license on diagnostic test for the detection of anti-CRMP5 antibodies, and travel grants from LFB. J-CA and J-PC also participated to a patent on the detection of FGFR3 antibodies. CR, KF, FL, ER-F, MCFJ and ARMM report no disclosure relevant to the manuscript.

      • Patient consent for publication Not required.

      • Ethics approval Ethical approval for the study was provided by the ethical committee of the University Hospital of Saint-Etienne (Clinical trial #NCT02539329) and by the committee for the protection of persons (n°2014-27).

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Data availability statement Data are available upon reasonable request.

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