MOG encephalomyelitis: international recommendations on diagnosis and antibody testing

S Jarius, F Paul, O Aktas, N Asgari, R C Dale, J de Seze, D Franciotta, K Fujihara, A Jacob, H J Kim, I Kleiter, T Kümpfel, M Levy, J Palace, K Ruprecht, A Saiz, C Trebst, B G Weinshenker, B Wildemann, S Jarius, F Paul, O Aktas, N Asgari, R C Dale, J de Seze, D Franciotta, K Fujihara, A Jacob, H J Kim, I Kleiter, T Kümpfel, M Levy, J Palace, K Ruprecht, A Saiz, C Trebst, B G Weinshenker, B Wildemann

Abstract

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.

Keywords: Antibody testing; Consensus recommendations; Diagnosis; Multiple sclerosis (MS); Myelin oligodendrocyte glycoprotein (MOG) antibodies; Neuromyelitis optica spectrum disorders (NMOSD); Optic neuritis (ON), Myelitis.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Competing interests

OA has received grants by the German Research Foundation (DFG), the German Ministry for Education and Research (BMBF) (KKNMS; for NEMOS NationNMO FKZ 01GI1602), speaking fees and travel grants by Bayer, Biogen, Genzyme, Medimmune, Merck, Novartis, Roche, Sanofi, and Teva.

DF received one honorarium for a presentation from Biogen not related to the present paper.

KF serves on the advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Alexion Pharmaceuticals, and Medimmune; has received travel funding and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; is on the editorial board for Clinical and Experimental Neuroimmunology; is an advisory board member for Sri Lanka Journal of Neurology; and received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, OnoPharmaceutical, Nihon Pharmaceutical, Genzyme Japan, Ministry of Education, Science and Technology of Japan, and Ministry of Health, Welfare and Labor of Japan.

AJ is supported by the NHS National Specialised Commissioning Group for NMO and has been a consultant for Shire, Alexion, Terumo-BCT and Chugai pharmaceuticals and has received research funding from Biogen and Alexion pharamaceuticals.

HJK has lectured, consulted, and received honoraria from Bayer Schering Pharma, Biogen, Genzyme, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Teva-Handok, and UCB; received a grant from the Ministry of Science, ICT & Future Planning; and accepted research funding from Genzyme, Kael-GemVax, Merck Serono, Teva-Handok, and UCB; serves on a steering committee for MedImmune; is a co-editor for the Multiple Sclerosis Journal – Experimental, Translational, and Clinical, and an associated editor for the Journal of Clinical Neurology.

IK has received honoraria for consultancy or lectures and travel reimbursement from Bayer Health Care, Biogen Idec, Chugai, Novartis, Shire and Roche and grant support from Biogen Idec, Novartis, Chugai and Diamed.

TK has received travel expenses and personal compensations from Bayer Healthcare, Teva Pharma, Merck-Serono, Novartis, Sanofi Genzyme and Biogen-Idec as well as grant support from Chugai Pharma and Novartis.

ML receives support from Quest Diagnostics.

JP has received support for scientific meetings and honorariums for advisory work from Merck Serono, ABIDE, Biogen Idec, Novartis, Alexion, Medimmune, Teva, Chugai Pharma and Bayer Schering, and unrestricted grants from Merck Serono, Novartis, Biogen Idec and Bayer Schering. Grants from the MS society. GMSI, NIHR and Guthy- Jackson Foundation for research studies. She runs a nationally commissioned service for neuromyelitis optica and congenital myasthenia.

FP has received honoraria and research support from Alexion, Bayer, Biogen, Chugai, MerckSerono, Novartis, Genyzme, MedImmune, Shire, Teva, and serves on scientific advisory boards for Alexion, MedImmune and Novartis. He has received funding from Deutsche Forschungsgemeinschaft (DFG Exc 257), German Federal Ministry for Education and Research (Competence Network Multiple Sclerosis), Guthy Jackson Charitable Foundation, EU Framework Program 7, National Multiple Sclerosis Society of the USA.

KR has received research support from the German Federal Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and Novartis as well as travel grants or speaking fees from the Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, and Novartis.

AS is supported by La Marató de TV3 (20141830).

CT has received honoraria for consultation and expert testimony from Bayer Vital GmbH, Biogen Idec/GmbH, Genzyme GmbH and Novartis Pharmaceuticals. None of this interfered with the current report.

BGW receives royalties from RSR Ltd., Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders. He receives personal compensation for serving as a member of an adjudication committee for clinical trials in NMO being conducted by MedImmune and Alexion pharmaceutical companies. He is a consultant for Caladrius Biosciences regarding a clinical trial for NMO. He receives personal compensation for serving on a data safety monitoring board for Novartis for clinical trials in MS.

The work of BW was supported by research grants from the Dietmar Hopp Foundation, from Merck Serono and from the German Federal Ministry of Education and Research (Competence Network Multiple Sclerosis).

SJ, NA, RCD, and JDS declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Source: PubMed

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