MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin

• DOI: 10.1186/s12974-016-0717-1
• Publication Date: 2016-10-27T14:25:48Z
• Authors: Sven Jarius; Klemens Ruprecht; Ingo Kleiter; Nadja Borisow; Nasrin Asgari; Kalliopi Pitarokoili; Florence Pache; Oliver Stich; Lena-Alexandra Beume; Martin W. Hümmert; Corinna Trebst; Marius Ringelstein; Orhan Aktas; Alexander Winkelmann; Mathias Buttmann; Alexander Schwarz; Hanna Zimmermann; Alexander U. Brandt; Diego Franciotta; Marco Capobianco; Joseph Kuchling; Jürgen Haas; Mirjam Korporal-K...; Soeren Thue Lille...; Kai Fechner; Kathrin Schanda; Friedemann Paul; Brigitte Wildemann; Markus Reindl
• Keywords: Adult; Male; Aquaporin-4 antibodies (AQP4-IgG); Immunology; Neuromyelitis optica antibodies (NMO-IgG); 610; Optic neuritis; Transfection; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit; Severity of Illness Index; Multiple sclerosis; Cellular and Molecular Neuroscience; 610 Medical sciences Medicine; Humans; Neuromyelitis optica spectrum disorders (NMOSD); Transverse Myelitis; Devic’s syndrome; Autoantibodies; Aquaporin 4; ddc:610; Research; Devic's syndrome; Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG); Neuromyelitis Optica; Cell-based assays; Myelitis; 3. Good health; Neuromyelitis optica (NMO); Longitudinally extensive transverse myelitis (LETM); Cerebrospinal fluid; HEK293 Cells; Neurology; Female; Myelin-Oligodendrocyte Glycoprotein; Function and Dysfunction of the Nervous System; Antibody index

Background Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders. Objective To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers. Methods 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full- length human MOG-transfected HEK293A cells. Results MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7%) patients with a history of both ON and myelitis, 22/103 (21.4%) with a history of ON but no myelitis and 6/45 (13.3%) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67%) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89%) follow-up samples obtained over a median period of 16.5 months (range 0–123). Serum titers were higher during attacks than during remission (p