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.
Kaneko, Kimihiko 1; Sato, Douglas Kazutoshi 1,2,3; Nakashima, Ichiro 1,4; Ogawa, Ryo 1; Akaishi, Tetsuya 1,5; Takai, Yoshiki 1; Nishiyama, Shuhei 1; Takahashi, Toshiyuki 1,5; Misu, Tatsuro 1; Kuroda, Hiroshi 1; Tanaka, Satoru 6; Nomura, Kyoichi 6; Hashimoto, Yuji 7; Callegaro, Dagoberto 3; Steinman, Lawrence 8; Fujihara, Kazuo 1,9,10; Aoki, Masashi 1
[Article]
Journal of Neurology, Neurosurgery & Psychiatry.
89(9):927-936, September 2018.
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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-[gamma], IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1[alpha] 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.
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