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J Neurol Neurosurg Psychiatry. 2018 Sep;89(9):927-936. doi: 10.1136/jnnp-2018-317969. Epub 2018 Jun 6.

CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications.

Author information

1
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
2
Department of Neurology, Brain Institute and Hospital Sao Lucas Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
3
Department of Neurology, São Paulo University, São Paulo, Brazil.
4
Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
5
Department of Neurology, Yonezawa National Hospital, Yonezawa, Japan.
6
Department of Neurology, Saitama Medical University, Kawagoe, Japan.
7
Department of Pediatrics, Chiba Kaihin Municipal Hospital, Chiba, Japan.
8
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
9
Department of Multiple Sclerosis Therapeutics, Fukushima Medical University, Fukushima, Japan.
10
Multiple Sclerosis and Neuromyelitis Optica Center, Tohoku Research Institute for Neuroscience, Koriyama, Japan.

Abstract

OBJECTIVE:

To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients.

METHODS:

In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14).

RESULTS:

In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases.

CONCLUSIONS:

The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets.

KEYWORDS:

aquaporin-4-IgG; cytokine profile; demyelinating disease; multiple sclerosis; myelin oligodendrocyte glycoprotein-IgG; neuromyelitis optica spectrum disorders

Conflict of interest statement

Competing interests: DKS has received a scholarship from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI 15K19472), research support from CAPES/Brazil (CSF-PAJT—88887.091277/ 2014-00) and speaker honoraria from Novartis. IN has received funding for travel and received speaker honoraria from Mitsubishi Tanabe Pharma Corporation and has received research funding from LSI Medience Corporation and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. YT has received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. SN has received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. TM has received speaker honoraria from Bayer Schering Pharma, Biogen Idec Japan, Mitsubishi Tanabe Pharma Corporation, Asahi Kasei Medical and Astellas Pharma, and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical, Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Teijin Pharma, and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labour and Welfare of Japan. HK has received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. KN reports personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from Astellas Pharma, personal fees from Chemo-Sero-Therapeutic Research Institute and personal fees from Teijin Pharma. LS served on the scientific advisory board for Novartis, Receptos, Atreca, Tolerion and Teva, received travel funding and/or speaker honoraria from Biogen, Bayhill, Bayer, Celgene and Receptos, is on the editorial board for Multiple Sclerosis Journal and Proceedings of the National Academy of Science, holds patents for antigen-specific tolerance, has a patent pending for cytokines and type 1 interferons, is on the speakers' bureau for EMD Serono, received research support from NIH, has stock options and board membership in Tolerion, and is on the board of directors for BioAtla. KF serves on the scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, MedImmune and Medical Review; has received funding for travel and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma, Takeda Pharmaceutical Company, Asahi Kasei Medical, Daiichi Sankyo and Nihon Pharmaceutical; serves as an editorial board member of Clinical and Experimental Neuroimmunology (2009–present) and an advisory board member of Sri Lanka Journal of Neurology; has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical and Genzyme Japan; is funded by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#22229008, 2010-2015; #26293205, 2014-2016) and by the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labour of Japan (2010–present). MA has received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labour and Welfare of Japan.

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