Identification of galectin-3 as a possible antibody target for secondary progressive multiple sclerosis. (March 2017)

• Record Type: Journal Article
• Authors: Nishihara, Hideaki; Shimizu, Fumitaka; Kitagawa, Takao; Yamanaka, Nanami; Akada, Junko; Kuramitsu, Yasuhiro; Sano, Yasuteru; Takeshita, Yukio; Maeda, Toshihiko; Abe, Masaaki; Koga, Michiaki; Nakamura, Kazuyuki; Kanda, Takashi
• Is Part Of: Multiple sclerosis. Volume 23:Number 3(2017)
• Page Start: 382
• Page End: 394
• Publication Date: 2017-03
• Subjects: Galectin-3 -- blood–brain barrier -- secondary progressive multiple sclerosis; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458516655217
• Languages: English
• ISSNs: 1352-4585

Abstract

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 (NFκ) B p65 expression in the BMECs. Exposure to SPMS patients' sera also increased the protein levels of ICAM-1 and phospho-NFκB 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.