Effect of Sera from Bickerstaff Brainstem Encephalitis and Miller Fisher Syndrome Patients Against Human Blood-Brain Barrier and Blood-Nerve Barrier In Vitro Models (P06.141)

Objective: Antibody against GQ1b is frequently detected in Bickerstaff brainstem encephalitis (BBE) and Miller Fisher syndrome (MFS) and has been considered to be pathogenically important in the development of these two disorders; however, the clinical manifestations of there two disorders are obviously different. We hypothesized that there phenotypic differences may be derived from the difference of blood-brain barrier (BBB)/ blood-nerve barrier(BNB) breakdown. Background We demonstrated the effects of sera from patients with BBE and MFS on the impairment of BBB or BNB function and clarified the roles of humoral factor such as Matrix metalloproteinases(MMP) in the destruction of BBB or BNB. Design/Methods: Both human BBB and BNB-derived endothelial cell lines were recently developed in Yamaguchi University, named TY10 and PnMECs. We evaluated transendothelial electrical resistance (TEER), the amount of tight junction proteins including claudin-5 and occludin, and the amount of MMP including MMP-9 and MMP-2 by western blotting in TY10 and PnMECs after the exposure of the patients9 sera. Results: The amount of claudin-5 protein in TY10, not in PnMECs, decreased after exposure of BBE sera. TEER of TY10 also decreased after application of BBE sera. Sera from MFS patients had no effect in these experiments. The amount of MMP-9 and MMP-2 protein in TY10 increased after exposure of BBE sera. Conclusions: Only sera from BBE patients disrupt BBB. This may partially explain the phenotypic defferences between BBE and MFS. BBE sera break BBB, possibly via autocrine secretion of MMP-9 and MMP-2 from BBB-composing endothelial cells. Disclosure: Dr. Saito has nothing to disclose. Dr. Shimizu has nothing to disclose. Dr. Koga has nothing to disclose. Dr. Sano has nothing to disclose. Dr. Haruki has nothing to disclose. Dr. Maeda has nothing to disclose. Dr. Abe has nothing to disclose. Dr. Tasaki has nothing to disclose. Dr. Suzuki has nothing to disclose. Dr. Kusunoki has nothing to disclose. Dr. Mizusawa has received personal compensation for activities with Tanabemitsubishi Co and Sanofi-Aventis Co. Dr. Mizusawa has received personal compensation in an editorial capacity for No to Shinkei and Clinical Neuroscience. Dr. Kanda has nothing to disclose.