TY - JOUR
T1 - CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS
T2 - A cross-sectional study and potential therapeutic implications
AU - Kaneko, Kimihiko
AU - Sato, Douglas Kazutoshi
AU - Nakashima, Ichiro
AU - Ogawa, Ryo
AU - Akaishi, Tetsuya
AU - Takai, Yoshiki
AU - Nishiyama, Shuhei
AU - Takahashi, Toshiyuki
AU - Misu, Tatsuro
AU - Kuroda, Hiroshi
AU - Tanaka, Satoru
AU - Nomura, Kyoichi
AU - Hashimoto, Yuji
AU - Callegaro, Dagoberto
AU - Steinman, Lawrence
AU - Fujihara, Kazuo
AU - Aoki, Masashi
N1 - Funding Information:
Funding This study was partially supported by a Grant-in-aid for scientific Research from the Japan society for the promotion of science (KaKeNhI), and the health and Labour sciences Research Grant on Intractable Diseases (neuroimmunological diseases) from the Ministry of health, Labour and Welfare of Japan. This study was not industry-sponsored.
Publisher Copyright:
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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-3, 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.
AB - 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-3, 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.
KW - aquaporin-4-IgG
KW - cytokine profile
KW - demyelinating disease
KW - multiple sclerosis
KW - myelin oligodendrocyte glycoprotein-IgG
KW - neuromyelitis optica spectrum disorders
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U2 - 10.1136/jnnp-2018-317969
DO - 10.1136/jnnp-2018-317969
M3 - Article
C2 - 29875186
AN - SCOPUS:85048264054
SN - 0022-3050
VL - 89
SP - 927
EP - 936
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 9
ER -
