Journal
MULTIPLE SCLEROSIS JOURNAL
Volume 23, Issue 3, Pages 382-394Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458516655217
Keywords
Galectin-3; blood-brain barrier; secondary progressive multiple sclerosis
Categories
Funding
- Japan Society for the Promotion of Science, Tokyo, Japan [24790886, 22790821, 23659457, 25293203, 26670443]
- Health and Labor Sciences Research Grants for Research on Intractable Diseases (Neuroimmunological Disease Research Committee) from the Ministry of Health, Labour and Welfare of Japan [K2002528]
- National Center of Neurology and Psychiatry [25-4]
- Yamaguchi University Hospital
- Ministry of Health, Labour and Welfare of Japan
- Grants-in-Aid for Scientific Research [15K08464, 26670443, 24790886, 16H07008, 23659457, 25293203] Funding Source: KAKEN
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Background: Recent studies have revealed that the disruption of the blood-brain barrier (BBB) might contribute to the induction of neurodegeneration in the progressive stage of multiple sclerosis (MS). Objective: We investigated a potential target for the serum auto-antibodies responsible for the BBB impairment in patients with secondary progressive MS (SPMS). Methods: We identified undetermined target antigens in human brain microvascular endothelial cells (BMECs) that reacted with auto-antibodies in sera from SPMS patients using a proteomic approach. In addition, we examined how the identified auto-antibodies compromise the BBB integrity. Results: We found that 10 of 11 SPMS sera had auto-antibodies against galectin-3, although the patients with other neurological diseases did not have these antibodies. Downregulation of galectin-3 led to elevated intercellular adhesion molecule-1 (ICAM-1) and phospho-nuclear factor-kappa (NF) B p65 expression in the BMECs. Exposure to SPMS patients' sera also increased the protein levels of ICAM-1 and phospho-NFB p65 in BMECs, but these effects induced by anti-galectin-3 immunoreactivity were canceled by the downregulation of galectin-3. Conclusion: Galectin-3 is a possible immunological target molecule of the pathogenic auto-antibodies and contributes to the persistent BBB breakdown in patients with SPMS. These antibodies may also serve as a novel biomarker for SPMS.
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