Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy
Por:
Pascual-Goni, E, Fehmi, J, Lleixa, C, Martin-Aguilar, L, Devaux, J, Hoftberger, R, Delmont, E, Doppler, K, Sommer, C, Radunovic, A, Carvajal, A, Smyth, S, Williams, L, Mazanec, R, Potockova, V, Hinds, N, Cassereau, J, Viala, K, Lefilliatre, M, Nicolas, G, Foley, P, Leypoldt, F, Keddie, S, Lunn, MP, Zimprich, F, Nunkoo, VS, Loscher, WN, Martinez-Martinez, L, Diaz-Manera, J, Rojas-Garcia, R, Illa, I, Rinaldi, S, Querol, L
Publicada:
1 abr 2021
Resumen:
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 (hut 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- 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 ("enervation were frequent in elecmphysiological studies. Complete response to intraenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunobistochemistry 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 HASA. AU 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 ELBA. 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.
Filiaciones:
Pascual-Goni, E:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Fehmi, J:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford, England
Lleixa, C:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Martin-Aguilar, L:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Devaux, J:
Hosp St Eloi, Inst Neurosci Montpellier, Montpellier, France
Hoftberger, R:
Med Univ Vienna, Dept Neurol, Div Neuropathol & Neurochem, Vienna, Austria
Delmont, E:
Hosp La Timone, Referral Ctr ALS & Neuromuscular Dis, Marseille, France
Doppler, K:
Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany
Sommer, C:
Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany
Radunovic, A:
Barts Hlth NHS Trust, Dept Neurol, London, England
Carvajal, A:
Complejo Hosp Univ Granada, Granada, Spain
Smyth, S:
Mater Misericordiae Univ Hosp, Dublin, Ireland
Williams, L:
Mater Misericordiae Univ Hosp, Dublin, Ireland
Mazanec, R:
Charles Univ Prague, Dept Neurol, Med Fac, Prague, Czech Republic
Univ Hosp Motol, Prague, Czech Republic
Potockova, V:
Charles Univ Prague, Dept Neurol, Med Fac, Prague, Czech Republic
Univ Hosp Motol, Prague, Czech Republic
Hinds, N:
Abertawe Bro Morgannwg Univ Hlth Board, Swansea, W Glam, Wales
Cassereau, J:
Angers Univ Hosp, Reference Ctr Neuromuscular Dis, Dept Neurol, Angers, France
Viala, K:
Hosp Pitie Salpetriere, Dept Clin Neurophysiol, Paris, France
Lefilliatre, M:
Hosp Ctr Univ Caen, Dept Neurol, Caen, France
Nicolas, G:
Univ Versailles St Quentin Yvelines, Dept Neurol, Hop Raymond Poincare, Garches, France
Foley, P:
Univ Edinburgh, Anne Rowling Regenerat Neurol Clin, Edinburgh, Midlothian, Scotland
Leypoldt, F:
Univ Hosp Schleswig Holstein, Inst Clin Chem, Kiel, Germany
Christian Albrechts Univ Kiel, Dept Neurol, Kiel, Germany
Keddie, S:
Natl Hosp Neurol & Neurosurg, Ctr Neuromuscular Dis, Queen Sq, London, England
Lunn, MP:
Natl Hosp Neurol & Neurosurg, Ctr Neuromuscular Dis, Queen Sq, London, England
Zimprich, F:
Med Univ Vienna, Dept Neurol, Vienna, Austria
Nunkoo, VS:
Municipal Univ Hosp Dr Gavril Curteanu, Dept Neurol, Oradea, Romania
Loscher, WN:
Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria
Martinez-Martinez, L:
Univ Autonoma Barcelona, Dept Immunol, Hosp Santa Creu & St Pau, Barcelona, Spain
Diaz-Manera, J:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Valencia, Spain
Rojas-Garcia, R:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Valencia, Spain
Illa, I:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Valencia, Spain
Rinaldi, S:
Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford, England
Querol, L:
Univ Autonoma Barcelona, Neuromuscular Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Valencia, Spain
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