Anti-Glycolipid Antibody Examination in Five EAE Models and Theiler’s Virus Model of Multiple Sclerosis: Detection of Anti-GM1, GM3, GM4, and Sulfatide Antibodies in Relapsing-Remitting EAE
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Published:2023-08-18
Issue:16
Volume:24
Page:12937
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Moriguchi Kota12, Nakamura Yumina13, Park Ah-Mee14, Sato Fumitaka1ORCID, Kuwahara Motoi5, Khadka Sundar16ORCID, Omura Seiichi1ORCID, Ahmad Ijaz1, Kusunoki Susumu57, Tsunoda Ikuo1ORCID
Affiliation:
1. Department of Microbiology, Faculty of Medicine, Kindai University, Osakasayama City 589-8511, Osaka, Japan 2. Department of Internal Medicine, Japan Self Defense Forces Hanshin Hospital, Kawanishi City 666-0024, Hyogo, Japan 3. Department of Life Science, Faculty of Science and Engineering, Kindai University, Higashiosaka City 577-8502, Osaka, Japan 4. Department of Arts and Science, Faculty of Medicine, Kindai University, Osakasayama City 589-8511, Osaka, Japan 5. Department of Neurology, Faculty of Medicine, Kindai University, Osakasayama City 589-8511, Osaka, Japan 6. Department of Immunology, School of Medicine, Duke University, Durham, NC 27710, USA 7. Japan Community Health Care Organization (JCHO) Headquarters, Minato City 108-8583, Tokyo, Japan
Abstract
Anti-glycolipid antibodies have been reported to play pathogenic roles in peripheral inflammatory neuropathies, such as Guillain–Barré syndrome. On the other hand, the role in multiple sclerosis (MS), inflammatory demyelinating disease in the central nervous system (CNS), is largely unknown, although the presence of anti-glycolipid antibodies was reported to differ among MS patients with relapsing-remitting (RR), primary progressive (PP), and secondary progressive (SP) disease courses. We investigated whether the induction of anti-glycolipid antibodies could differ among experimental MS models with distinct clinical courses, depending on induction methods. Using three mouse strains, SJL/J, C57BL/6, and A.SW mice, we induced five distinct experimental autoimmune encephalomyelitis (EAE) models with myelin oligodendrocyte glycoprotein (MOG)35–55, MOG92–106, or myelin proteolipid protein (PLP)139–151, with or without an additional adjuvant curdlan injection. We also induced a viral model of MS, using Theiler’s murine encephalomyelitis virus (TMEV). Each MS model had an RR, SP, PP, hyperacute, or chronic clinical course. Using the sera from the MS models, we quantified antibodies against 11 glycolipids: GM1, GM2, GM3, GM4, GD3, galactocerebroside, GD1a, GD1b, GT1b, GQ1b, and sulfatide. Among the MS models, we detected significant increases in four anti-glycolipid antibodies, GM1, GM3, GM4, and sulfatide, in PLP139–151-induced EAE with an RR disease course. We also tested cellular immune responses to the glycolipids and found CD1d-independent lymphoproliferative responses only to sulfatide with decreased interleukin (IL)-10 production. Although these results implied that anti-glycolipid antibodies might play a role in remissions or relapses in RR-EAE, their functional roles need to be determined by mechanistic experiments, such as injections of monoclonal anti-glycolipid antibodies.
Funder
Grant-in Aid for Scientific Research KAKENHI from the Japan Society for the Promotion of Science 2023 Kindai University Research Enhancement Grant All-Kindai University support project against COVID-19 Ministry of Education, Culture, Sports, Science and Technology, Japan through the Monbukagakusho (MEXT) Scholarship
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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