Connexin 43 Astrocytopathy Linked to Rapidly Progressive Multiple Sclerosis and Neuromyelitis Optica

摘要: Background Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology aggressiveness in Asian patients with MS NMO. Methods/Principal Findings Samples included 11 autopsied cases NMO spectrum disorder (NMOSD), six MS, 20 other neurological diseases (OND). Methods of analysis immunohistochemical expression astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative AQP4 proteins, extent demyelination, the vasculocentric deposition complement immunoglobulin, lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) inactive (n=23). Sera from 120 subjects including 30 NMO, 40 OND healthy controls examined anti-Cx43 antibody cell-based assay. Six NMO/NMOSD three showed preferential loss Cx43 beyond demyelinated areas lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions extensively lost. was significantly associated rapidly progressive course nine loss, but none eight without regardless phenotype, died within two years after onset (66.7% vs. 0%, P=0.0090). Overall, five had distal oligodendrogliopathy characterized selective myelin glycoprotein (55.6% 0.0%, P=0.0296). Loss Cx32 Cx47 observed most lesions all cases. Cx43-specific antibodies absent patients. Conclusions These findings suggest that autoantibody-independent may relate both NMO.