Glial Fibrillary Acidic Protein Autoimmunity A French Cohort Study

Alice Gravier-Dumonceau (1) , Roxana Ameli (2) , Veronique Rogemond (3, 4, 5, 6) , Anne Ruiz (1) , Bastien Joubert (4, 7) , Sergio Muniz-Castrillo (3, 4) , Alberto Vogrig (3, 4) , Geraldine Picard (3, 4, 5, 6) , Aditya Ambati (3, 4, 5, 6) , Marie Benaiteau (8) , Florence Rulquin , Jonathan Ciron (9, 8) , Kumaran Deiva (10) , Thomas De Broucker , Laurent Kremer (11) , Philippe Kerschen (12) , François Sellal (13) , Bastien Bouldoires , Roxana Genet , Julien Biberon (14) , Adrien Bigot (15) , Fanny Duval (16) , Nahema Issa (17) , Elena-Camelia Rusu , Mathilde Goudot (18) , Anais Dutray (19) , Jean Louis Devoize (20) , Lucie Hopes (18) , Anne-Laure Kaminsky (18) , Marion Philbert (21) , Eve Chanson (22) , Amelie Leblanc (23) , Erwan Morvan (24) , Daniela Andriuta (25, 26) , Philippe Diraison , Gabriel Mirebeau (27) , Celine Derollez , Veronique Bourg (28) , Quentin Bodard , Clementine Fort , Irina Grigorashvili-Coin , Guillaume Rieul (29) , Daniela Molinier-Tiganas , Mickael Bonnan (30) , Thierry Tchoumi , Jerome Honnorat (4, 7) , Romain Marignier (3)

1 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
2 Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL]
3 HCL - Hospices Civils de Lyon
4 INMG - Institut NeuroMyoGène
5 ICM - Institut du Cerveau = Paris Brain Institute
6 IMRB - Institut Mondor de Recherche Biomédicale
7 Centre de Référence Maladie Rare "Syndromes neurologiques Paranéoplasiques"
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
10 Service de neurologie [Le Kremlin Bicêtre]
11 CHU Strasbourg
12 ENT - Excitabilité nerveuse et thérapeutique
13 Hôpitaux Civils de Colmar
14 CPN - Centre Psychothérapique de Nancy [Laxou]
15 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
16 Groupe hospitalier Pellegrin
17 CHU Bordeaux [Bordeaux]
18 Service de neurologie [CHRU Nancy]
19 Centre Hospitalier Saint Jean de Perpignan
20 CH Angoulême - Centre Hospitalier d'Angoulême
21 UA UFR SM - Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud
22 CHU Clermont-Ferrand
23 Service de Neurologie [Brest]
24 CEA-LETI - Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information
25 Service de neurologie [Amiens]
26 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559
27 UGA UFRM - Université Grenoble Alpes - UFR Médecine
28 CHU - Hôpital Pasteur [Nice]
29 CHU de Saint-Brieuc
30 CHU Pau

Background and Objectives To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies. Methods We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAP alpha since 2017 from 2 French referral centers. Results We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score <= 2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies. Discussion GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

Domaines: Neurobiologie; Immunologie

Alice Gravier-Dumonceau, Roxana Ameli, Veronique Rogemond, Anne Ruiz, Bastien Joubert, et al.. Glial Fibrillary Acidic Protein Autoimmunity A French Cohort Study. Neurology, 2022, 98 (6), pp.E653-E668. ⟨10.1212/WNL.0000000000013087⟩. ⟨hal-03578197⟩