Junctional protein problems more indications of autoimmunity

Shimizu F, Tasaki A, Sano Y, Ju M, Nishihara H, Oishi M, Koga M, Kawai M, Kanda T. Sera from remitting and secondary progressive multiple sclerosis patients disrupt the blood-brain barrier. PLoS One. 2014 Mar;9(3):e92872.

BACKGROUND: Pathological destruction of blood-brain barrier (BBB) has been thought to be the initial key event in the process of developingmultiple sclerosis (MS). The purpose of the present study was to clarify the possible molecular mechanisms responsible for the malfunction of BBB by sera from relapse-remitting MS (RRMS) and secondary progressive MS (SPMS) patients.

METHODS: We evaluated the effects of sera from the patients in the relapse phase of RRMS (RRMS-R), stable phase of RRMS (RRMS-S) and SPMS on the expression of tight junction proteins and vascular cell adhesion protein-1 (VCAM-1), and on the transendothelial electrical resistance (TEER) in human brain microvascular endothelial cells (BMECs).

RESULTS: Sera from the RRMS-R or SPMS patients decreased the claudin-5 protein expression and the TEER in BMECs. In RRMS-R, this effect was restored after adding an MMP inhibitor, and the MMP-2/9 secretion by BMECs was significantly increased after the application of patients’ sera. In SPMS, the immunoglobulin G (IgG) purified from patients’ sera also decreased the claudin-5 protein expression and the TEER in BMECs. The sera and purified IgG from all MS patients increased the VCAM-1 protein expression in BMECs.
CONCLUSIONS: The up-regulation of autocrine MMP-2/9 by BMECs after exposure to sera from RRMS-R patients or the autoantibodies against BMECs from SPMS patients can compromise the BBB. Both RRMS-S and SPMS sera increased the VCAM-1 expression in the BBB, thus indicating that targeting the VCAM-1 in the BBB could represent a possible therapeutic strategy for even the stable phase of MS and SPMS.

Claudin is a protein that is found in the junctions between cells in the blood vessel. There is something in the blood of MSers that influence the tightness of the gaps between blood vessel wall cells.

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  • It's always interesting to read papers on BBB disruption. Is there any theory on the role EBV may play in this process? Is VCAM/VLA expression by endothelium and lymphocytes activated by chronic EBV?

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