Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.

Abertawe Bro Morgannwg University Health Board Swansea Wales UK

Anne Rowling Regenerative Neurology Clinic University of Edinburgh Edinburgh UK

Centre for Neuromuscular Diseases National Hospital for Neurology and Neurosurgery Queen Square London UK

Centro para la Investigación Biomédica en Red de Enfermedades Raras Spain

Complejo Hospitalario Universitario de Granada Granada Spain

Department of Clinical Neurophysiology Hospital de la Pitié Salpêtrière Paris France

Department of Immunology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain

Department of Neurology Barts Health NHS Trust London UK

Department of Neurology Christian Albrechts Universität zu Kiel Kiel Germany

Department of Neurology Hôpital Raymond Poincaré Université Versailles Saint Quentin en Yvelines Garches France

Department of Neurology Hospital Center University of Caen Caen France

Department of Neurology Medical Faculty of Charles University and University Hospital Motol Prague Czech Republic

Department of Neurology Medical University of Innsbruck Austria

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Municipal University Hospital Dr Gavril Curteanu Oradea Romania

Department of Neurology University Hospital Würzburg Würzburg Germany

Division of Neuropathology and Neurochemistry Department of Neurology Medical University of Vienna Vienna Austria

Institut de Neurosciences de Montpellier Hospital Saint Eloi Montpelier France

Institute of Clinical Chemistry University Hospital Schleswig Holstein Kiel Germany

Mater Misericordiae University Hospital Dublin Republic of Ireland

Neuromuscular Diseases Unit Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Spain

Nuffield Department of Clinical Neurosciences University of Oxford John Radcliffe Hospital Oxford UK

Reference Centre for Neuromuscular Diseases Department of Neurology Angers University Hospital Angers France

Referral Centre for ALS and Neuromuscular Diseases Hospital La Timone Marseille France

Brain. 2021 May 7;144(4):1043-1045. doi: 10.1093/brain/awab116. PubMed

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