title: Identification of galectin-3 as a possible antibody target for secondary progressive multiple sclerosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nishihara
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan/Biogen, Cambridge, MA, USA.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Shimizu
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kitagawa
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Nanami
authors.initials: N
authors.lastname: Yamanaka
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi University, Ube, Japan/Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Akada
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuramitsu
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takeshita
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi University, Ube, Japan; Centre of Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D001798:Blood Proteins; D001812:Blood-Brain Barrier / Q000473:pathology*; D001921:Brain / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D037161:Galectins; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D040901:Proteomics; D055815:Young Adult
chemical_list: D000906:Antibodies; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human
keywords: Galectin-3; blood–brain barrier; secondary progressive multiple sclerosis