ECTRIMS eLearning

Pro-inflammatory cytokine elevation in MOG-Ab+, AQP4-Ab+ disorder and MS
Author(s): ,
K Kaneko
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
D.K Sato
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan;São Paulo University, São Paulo;Brain Institute and Hospital Sao Lucas Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
,
R Ogawa
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
T Akaishi
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
Y Takai
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
S Nishiyama
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
T Takahashi
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan;Department of Neurology, NHO Yonezawa Hospital, Yonazawa
,
T Misu
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan;Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai
,
H Kuroda
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
S Tanaka
Affiliations:
Department of Neurology, Saitama Medical Center, Kawagoe
,
I Nakashima
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
,
K Nomura
Affiliations:
Department of Neurology, Saitama Medical Center, Kawagoe
,
D Callegaro
Affiliations:
São Paulo University, São Paulo
,
K Fujihara
Affiliations:
Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai;Department of Neurology, Fukushima Medical University, Fukushima, Japan
M Aoki
Affiliations:
Department of Neurology, Tohoku University, Sendai, Japan
ECTRIMS Learn. Kaneko K. 09/15/16; 146226; P386
Kimihiko Kaneko
Kimihiko Kaneko
Contributions
Abstract

Abstract: P386

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Pathology

Objective: To examine acute phase cerebrospinal fluid(CSF) cytokine levels in myelin oligodendrocyte glycoprotein(MOG)-Ab+ cases, compare the result with the clinical and laboratory findings, and then compare the results with those in aquaporin4(AQP4)-Ab+ cases, multiple sclerosis (MS), and non-inflammatory cases.

Methods: We measured 27 cytokine/chemokines by multiplex fluorescent bead-based immunoassays, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) level by commercially available ELISA assays in the CSF of 26 MOG-Ab+(>18yo: n=13, < 18yo: n=13), AQP4-Ab+(n=19), MS(n=12), non-inflammatory neurological diseases (n=16). In patients with MOG-Ab+ and AQP4-Ab+, antibody status was examined both in serum and CSF using cell-based assays. Samples were collected in acute phase (< 30 days from onset) before treatment except for non-inflammatory cases. Results were analyzed with clinical information, antibody titer, and CSF routine examination.

Results: IL-6,IP-10, and IFN-1ra were significantly elevated in MOG-Ab+ and AQP4-Ab+ cases as compare with MS. IL-10 and IL-15 were higher in MOG-Ab+ cases than in MS. G-CSF was significantly higher in MOG-Ab+ cases than in AQP4-Ab+ cases and MS while GM-CSF was much higher in MS than in MOG-Ab+ and AQP4-Ab+ cases. Cytokines levels were not different in various clinical phenotypes (ADEM, NMOSD, myelitis, and optic neuritis) of MOG-Ab+ cases. In comparison of adult and pediatric cases , IL17A was significantly elevated in adult group. Unlike significant association between AQP4-Ab titers/IL-6 and GFAP in AQP4-Ab+ cases, there was only mild associations between serum/CSF MOG-Ab titers, cytokine orroutine CSF findings and CSF-MBP level in MOG-Ab+ cases.

Conclusion: In MOG-Ab+ cases, cytokine profile including significantly elevated IL-6 was largely similar to AQP4-Ab+ cases but was different from MS. However, considering the relatively mild correlation between MOG-Ab titers/IL-6 and MBP level as compared with AQP4-Ab+ cases, in addition to MOG-Ab, other pathogenetic factors, such as T, B and other immune cells, may be needed in the lesion development in MOG-Ab+ diseases.

Disclosure: Kimihiko Kaneko: no discloser

Douglas Kazutoshi Sato: a scholarship from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (KAKENHI 15K19472), research support from CAPES/Brasil (CSF-PAJT—88887.091277/ 2014-00) and speaker honoraria from Novartis

Ryo Ogawa: nothing to disclos

Yoshiki Takai: nothing to disclose

Shuei Nishiyama: nothing todisclose

Toshiyuki Takahashi: nothing to disclose

Tatsuro Misu: speaker honoraria from Bayer Schering Pharma, Biogen Idec Japan, Mitsubishi Tanabe Pharma Corporation, Asahi Kasei Medical Co, and Astellas Pharma Inc, and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical Co, The 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, Science and Technology, and the Ministry of Health, Labor and Welfare of Japan

Hiroshi Kuroda: grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan

Satoru Tanaka: nothing to disclose

Ichiro Nakashima: grants from Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and from Ministry of Health, Labour and Welfare of Japan, personal fees from Mitsubishi Tanabe Pharma Corporation, Biogen Idec Japan, Novartis Pharmaceuticals Japan, Bayer Yakuhin, Ltd, and grants from LSI Medience Corporation; SN JSPS KAKENHI Grant (Grant-in-Aid for Young Scientists(B)) Number 26860656; RM serves on the scientific advisory board for MedImmune and has received funding for travel and honoraria from Biogen Idec, Merck Serono,Novartis, Sanofi-Genzyme and Teva

Kyoichi Nomura: personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from Astellas Pharma Inc, personal fees from Chemo-Sero-Therapeutic Research Institute and personal fees from Teijin Pharma

Dagoberto Callegaro: nothing to disclose

Kazuo Fujihara: 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 Inc, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc, Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co, Daiichi Sankyo and Nihon Pharmaceutical; serves as an editorial board member of Clinical and Experimental Neuroimmunology (2009-present) and is an advisory board member of Sri Lanka Journal of Neurology; has 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, Ono Pharmaceutical, Nihon Pharmaceutical and Genzyme Japan; and is funded as the secondary investigator (#22229008, 2010-2015) by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology of Japan and as the secondary investigatorby the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labor of Japan (2010-present).

Masashi Aoki: nothing to disclose

Abstract: P386

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Pathology

Objective: To examine acute phase cerebrospinal fluid(CSF) cytokine levels in myelin oligodendrocyte glycoprotein(MOG)-Ab+ cases, compare the result with the clinical and laboratory findings, and then compare the results with those in aquaporin4(AQP4)-Ab+ cases, multiple sclerosis (MS), and non-inflammatory cases.

Methods: We measured 27 cytokine/chemokines by multiplex fluorescent bead-based immunoassays, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) level by commercially available ELISA assays in the CSF of 26 MOG-Ab+(>18yo: n=13, < 18yo: n=13), AQP4-Ab+(n=19), MS(n=12), non-inflammatory neurological diseases (n=16). In patients with MOG-Ab+ and AQP4-Ab+, antibody status was examined both in serum and CSF using cell-based assays. Samples were collected in acute phase (< 30 days from onset) before treatment except for non-inflammatory cases. Results were analyzed with clinical information, antibody titer, and CSF routine examination.

Results: IL-6,IP-10, and IFN-1ra were significantly elevated in MOG-Ab+ and AQP4-Ab+ cases as compare with MS. IL-10 and IL-15 were higher in MOG-Ab+ cases than in MS. G-CSF was significantly higher in MOG-Ab+ cases than in AQP4-Ab+ cases and MS while GM-CSF was much higher in MS than in MOG-Ab+ and AQP4-Ab+ cases. Cytokines levels were not different in various clinical phenotypes (ADEM, NMOSD, myelitis, and optic neuritis) of MOG-Ab+ cases. In comparison of adult and pediatric cases , IL17A was significantly elevated in adult group. Unlike significant association between AQP4-Ab titers/IL-6 and GFAP in AQP4-Ab+ cases, there was only mild associations between serum/CSF MOG-Ab titers, cytokine orroutine CSF findings and CSF-MBP level in MOG-Ab+ cases.

Conclusion: In MOG-Ab+ cases, cytokine profile including significantly elevated IL-6 was largely similar to AQP4-Ab+ cases but was different from MS. However, considering the relatively mild correlation between MOG-Ab titers/IL-6 and MBP level as compared with AQP4-Ab+ cases, in addition to MOG-Ab, other pathogenetic factors, such as T, B and other immune cells, may be needed in the lesion development in MOG-Ab+ diseases.

Disclosure: Kimihiko Kaneko: no discloser

Douglas Kazutoshi Sato: a scholarship from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (KAKENHI 15K19472), research support from CAPES/Brasil (CSF-PAJT—88887.091277/ 2014-00) and speaker honoraria from Novartis

Ryo Ogawa: nothing to disclos

Yoshiki Takai: nothing to disclose

Shuei Nishiyama: nothing todisclose

Toshiyuki Takahashi: nothing to disclose

Tatsuro Misu: speaker honoraria from Bayer Schering Pharma, Biogen Idec Japan, Mitsubishi Tanabe Pharma Corporation, Asahi Kasei Medical Co, and Astellas Pharma Inc, and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical Co, The 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, Science and Technology, and the Ministry of Health, Labor and Welfare of Japan

Hiroshi Kuroda: grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan

Satoru Tanaka: nothing to disclose

Ichiro Nakashima: grants from Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and from Ministry of Health, Labour and Welfare of Japan, personal fees from Mitsubishi Tanabe Pharma Corporation, Biogen Idec Japan, Novartis Pharmaceuticals Japan, Bayer Yakuhin, Ltd, and grants from LSI Medience Corporation; SN JSPS KAKENHI Grant (Grant-in-Aid for Young Scientists(B)) Number 26860656; RM serves on the scientific advisory board for MedImmune and has received funding for travel and honoraria from Biogen Idec, Merck Serono,Novartis, Sanofi-Genzyme and Teva

Kyoichi Nomura: personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from Astellas Pharma Inc, personal fees from Chemo-Sero-Therapeutic Research Institute and personal fees from Teijin Pharma

Dagoberto Callegaro: nothing to disclose

Kazuo Fujihara: 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 Inc, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc, Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co, Daiichi Sankyo and Nihon Pharmaceutical; serves as an editorial board member of Clinical and Experimental Neuroimmunology (2009-present) and is an advisory board member of Sri Lanka Journal of Neurology; has 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, Ono Pharmaceutical, Nihon Pharmaceutical and Genzyme Japan; and is funded as the secondary investigator (#22229008, 2010-2015) by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology of Japan and as the secondary investigatorby the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labor of Japan (2010-present).

Masashi Aoki: nothing to disclose

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