Takashi Kanda1, Masanaga Yamawaki, Hidehiro Mizusawa. 1. Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School, Japan. t-kanda.nuro@tmd.ac.jp
Abstract
BACKGROUND: In Guillain-Barré syndrome (GBS), the destruction or malfunction of blood-nerve barrier (BNB) has been considered to be the beginning of the disease process. It is unclear whether sera from patients with GBS can open the BNB, and which component of patient sera is most important in the dysregulation of the BNB. METHODS: The authors evaluated the effect of sera from patients with GBS on permeability of an in vitro BNB model using bovine endoneurial microvascular endothelial cells (PnMEC) cultured on the luminal side of a collagen-coated culture insert (pore size: 0.4 micro m). RESULTS: PnMEC monolayers challenged by GBS sera showed significantly lower transendothelial electrical resistance and higher clearance of [carboxyl-(14)C]-inulin with or without complement. Sera with anti-GM1 antibody showed greater loosening of the barrier than others. This effect decreased significantly after incubation with pure GM1 antigen, suggesting the importance of anti-GM1 antibody in BNB dysregulation. Serial analyses of [carboxyl-(14)C]-inulin clearance in four patients disclosed a favorable effect of plasmapheresis in restoring BNB function in some cases. CONCLUSIONS: The authors found an unfavorable effect of sera from patients with GBS on BNB function, supporting involvement of humoral factors causing BNB derangement in the acute stage. Serial evaluation of permeability change using the authors' in vitro system might be useful for the clinical assessment of BNB derangement in individual patients.
BACKGROUND: In Guillain-Barré syndrome (GBS), the destruction or malfunction of blood-nerve barrier (BNB) has been considered to be the beginning of the disease process. It is unclear whether sera from patients with GBS can open the BNB, and which component of patient sera is most important in the dysregulation of the BNB. METHODS: The authors evaluated the effect of sera from patients with GBS on permeability of an in vitro BNB model using bovine endoneurial microvascular endothelial cells (PnMEC) cultured on the luminal side of a collagen-coated culture insert (pore size: 0.4 micro m). RESULTS: PnMEC monolayers challenged by GBS sera showed significantly lower transendothelial electrical resistance and higher clearance of [carboxyl-(14)C]-inulin with or without complement. Sera with anti-GM1 antibody showed greater loosening of the barrier than others. This effect decreased significantly after incubation with pure GM1 antigen, suggesting the importance of anti-GM1 antibody in BNB dysregulation. Serial analyses of [carboxyl-(14)C]-inulin clearance in four patients disclosed a favorable effect of plasmapheresis in restoring BNB function in some cases. CONCLUSIONS: The authors found an unfavorable effect of sera from patients with GBS on BNB function, supporting involvement of humoral factors causing BNB derangement in the acute stage. Serial evaluation of permeability change using the authors' in vitro system might be useful for the clinical assessment of BNB derangement in individual patients.