Emilien Delmont1,2, Alexandre Brodovitch3,4, Ludivine Kouton3, Thibaut Allou5, Stéphane Beltran6, Marion Brisset7, Jean Philippe Camdessanché8, Cécile Cauquil9, Jonathan Cirion10, Thierry Dubard11, Andoni Echaniz-Laguna9, Aude-Marie Grapperon3, Joëlle Jauffret11, Raul Juntas-Morales12, Laurent Daniel Kremer13,14, Thierry Kuntzer15, Céline Labeyrie9, Lucas Lanfranco16, Thierry Maisonobe17, Nicolas Mavroudakis18, Sylvie Mecharles-Darrigol19, Guillaume Nicolas7, Jean-Baptiste Noury20, Maud Perie21, Yusuf A Rajabally22, Gauthier Remiche18, Violaine Rouaud23, Céline Tard24, Emmanuelle Salort-Campana3, Annie Verschueren3, Karine Viala16, Adrien Wang25, Shahram Attarian3, José Boucraut26,4. 1. Referral Centre for Neuromuscular Diseases and ALS, La Timone Hospital, 264 Rue Saint Pierre, 13005, Marseille, France. emilien.delmont@ap-hm.fr. 2. Timone Neuroscience Institute, UMR CNRS 7289, Aix-Marseille University, 13005, Marseille, France. emilien.delmont@ap-hm.fr. 3. Referral Centre for Neuromuscular Diseases and ALS, La Timone Hospital, 264 Rue Saint Pierre, 13005, Marseille, France. 4. Immunology Laboratory, La Conception Hospital, Marseille, France. 5. Department of Neurology, Perpignan, France. 6. Department of Neurology, Tours, France. 7. Department of Neurology, APHP, Garches, France. 8. Department of Neurology, Saint Etienne, France. 9. Department of Neurology, CHU Bicetre, APHP, Paris, France. 10. Department of Neurology, Toulouse, France. 11. Department of Neurology, Reims, France. 12. Department of Neurology, Montpellier, France. 13. Department of Neurology, Strasbourg, France. 14. INSERM U1119, Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France. 15. Nerve Muscle Unit, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland. 16. Department of Nephrology, Brest, France. 17. Department of Neurology, APHP, Hôpital Pitié Salpêtrière, Paris, France. 18. Department of Neurology, Centre de Référence Neuromusculaire, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium. 19. Department of Neurology, Pointe A Pitre, France. 20. Department of Neurology, Brest, France. 21. Department of Neurology, Clermont-Ferrand, France. 22. Aston Medical School, Aston University, Birmingham, UK. 23. Department of Neurology, Vannes, France. 24. Department of Neurology, Lille, France. 25. Department of Neurology, Hôpital Foch, Paris, France. 26. Timone Neuroscience Institute, UMR CNRS 7289, Aix-Marseille University, 13005, Marseille, France.
Abstract
INTRODUCTION: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. METHODS: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. RESULTS: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). CONCLUSIONS: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.
INTRODUCTION: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. METHODS: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. RESULTS: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). CONCLUSIONS: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.