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Updated: Oct 14, 2025
Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
GRP78 Antibodies Are Associated With Blood-Brain Barrier Breakdown in Anti-Myelin Oligodendrocyte Glycoprotein
Fumitaka Shimizu1, Ryo Ogawa1, Yoichi Mizukami1
1From the Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine (F.S., K.H., C.K., Y.T., Y.S., M.F., T. Maeda, T.K.), Ube; Department of Neurology, Tohoku University Graduate School of Medicine (R.O., T.T., T. Misu), Sendai; Center for Gene Research (Y.M., K.W.), Yamaguchi University (Y.M., K.W.), Ube; Department of Neurology, National Hospital Organization Yonezawa Hospital (T.T.); Department of Neurology, Tohoku Medical and Pharmaceutical University (I.N.), Sendai; and Department of Multiple Sclerosis Therapeutics, Fukushima Medical University (K.F.), Japan.
Background And Objectives:
To analyze (1) the effect of immunoglobulin G (IgG) from patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disorder on the blood-brain barrier (BBB) endothelial cells and (2) the positivity of glucose-regulated protein 78 (GRP78) antibodies in MOG-Ab-associated disorders.
Methods:
IgG was purified from sera with patients with MOG-Ab-associated disorder in the acute phase (acute MOG, n = 15), in the stable stage (stable MOG, n = 14), healthy controls (HCs, n = 9), and disease controls (DCs, n = 27). Human brain microvascular endothelial cells (BMECs) were incubated with IgG, and the number of nuclear NF-κB p65-positive cells in BMECs using high-content imaging system and the quantitative messenger RNA change in gene expression over the whole transcriptome using RNA-seq were analyzed. GRP78 antibodies from patient IgGs were detected by Western blotting.
Results:
IgG in the acute MOG group significantly induced the nuclear translocation of NF-κB and increased the vascular cell adhesion molecule 1/intercellular adhesion molecule 1 expression/permeability of 10-kDa dextran compared with that from the stable MOG and HC/DC groups. RNA-seq and pathway analysis revealed that NF-κB signaling and oxidative stress (NQO1) play key roles. The NQO1 and Nrf2 protein amounts were significantly decreased after exposure to IgG in the acute MOG group. The rate of GRP78 antibody positivity in the acute MOG group (10/15, 67% [95% confidence interval, 38%-88%]) was significantly higher than that in the stable MOG group (5/14, 36% [13%-65%]), multiple sclerosis group (4/29, 14% [4%-32%]), the DCs (3/27, 11% [2%-29%]), or HCs (0/9, 0%). Removal of GRP78 antibodies from MOG-IgG reduced the effect on NF-κB nuclear translocation and increased permeability.
Discussion:
GRP78 antibodies may be associated with BBB dysfunction in MOG-Ab-associated disorder.
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