Blood-brain barrier dysfunction in immuno-mediated neurological diseases.

The blood-brain barrier (BBB) is the brain-specific endothelial cell barrier that is important for maintaining brain homeostasis and preventing the entry of toxic substances. Pathological BBB dysfunction is a critical step of the disease process in several immuno-mediated neurological diseases, including multiple sclerosis (MS), neuromyelitis optica (NMO), neuropsychiatric systemic lupus erythematosus (NPSLE) and neuro-Behçet diseases. The pathological findings from patients with secondary progressive (SP) MS, NMO and NPSLE showed leaky BBB in the active lesions. NMO is a disease with strong evidence of disease-specific and pathogenic autoantibodies (aquaporin 4 [AQP4] autoantibodies). In the development of NMO, circulating AQP4 autoantibodies need to pass through the BBB in order to reach AQP4 on the astrocyte endfeet. Strong evidence suggests that NPSLE is associated with the disruption of the BBB and NPSLE patients frequently have antibodies bound to endothelial cells in their sera. We recently identified two BBB-reactive autoantibodies in immuno-mediated neurological diseases: galectin-3 autoantibodies in SPMS and GRP78 autoantibodies in NMO. In the present review article, we describe the basic structure and cellular biology of the BBB, discuss recent insights regarding the pathophysiology of the BBB breakdown in the setting of immuno-mediated neurological diseases, and describe our recent findings of autoantibody-mediated BBB breakdown.