Contributions
Abstract: EP1456
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Neuromyelitis optica (NMO) is a neuroinflammatory disease characterized by severe optic neuritis and longitudinally extensive transverse myelitis. For many years NMO was believed to be a rare variant of multiple sclerosis (MS). In contrast to MS, autoantibodies against aquaporin-4 (AQP4), a water channel densely expressed on astrocytic end-feet, has been detected exclusively in sera from patients with NMO. Many studies have suggested that AQP4 autoantibodies are pathogenic, but the precise mechanism triggering inflammation and astrocyte impairment following anti-AQP4 Abs binding remains unknown. Some in vivo studies advocated for the role of complement system and neutrophils activation, while other highlighted glutamate pathological distribution as the main mechanism.
In this study we showed direct evidence of pathogenicity of the AQP4 Abs-positive serum derived from NMO patient, which by consecutive action of anti-AQP4 Abs, complement system and neutrophils triggered the reaction towards astrocytes. Based on our results we postulated the new theory about NMO pathogenesis which assumes that, there are two parallel-complementary mechanisms which can be initiated by anti-AQP4 autoantibody. First one was dependent on the complement cytotoxicity via C5b-C9 complex formation, and the second one was dependent on the reverse of astrocyte glutamate pomp into extracellular space on the C5a-preactivated neutrophils. As a consequence, part of the astrocytes was destroyed, however a certain population of astrocytes polarized into proinflammatory cells which characterized pathological glutamate removal from extracellular space.
Disclosure: This research was funded in part by grants from the National Science Centre (OPUS 2015/17/B/NZ6/04251 to P.L.; OPUS 2014/13/B/NZ6/00235 to P.L.); and the Medical University of Lodz (502-03/1-033-01/502-14-312 to P.P; 502-03/1-033-01/502-14-224 to M.D.).
Conflict of interest: The authors declare no competing financial interests
Paweł Piątek, Małgorzata Domowicz, Natalia Lewkowicz, Patrycja Przygodzka, Mariola Matysiak, Katarzyna Dzitko, Krzysztof W. Selmaj and Przemysław Lewkowicz: nothing to disclose.
Abstract: EP1456
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Neuromyelitis optica (NMO) is a neuroinflammatory disease characterized by severe optic neuritis and longitudinally extensive transverse myelitis. For many years NMO was believed to be a rare variant of multiple sclerosis (MS). In contrast to MS, autoantibodies against aquaporin-4 (AQP4), a water channel densely expressed on astrocytic end-feet, has been detected exclusively in sera from patients with NMO. Many studies have suggested that AQP4 autoantibodies are pathogenic, but the precise mechanism triggering inflammation and astrocyte impairment following anti-AQP4 Abs binding remains unknown. Some in vivo studies advocated for the role of complement system and neutrophils activation, while other highlighted glutamate pathological distribution as the main mechanism.
In this study we showed direct evidence of pathogenicity of the AQP4 Abs-positive serum derived from NMO patient, which by consecutive action of anti-AQP4 Abs, complement system and neutrophils triggered the reaction towards astrocytes. Based on our results we postulated the new theory about NMO pathogenesis which assumes that, there are two parallel-complementary mechanisms which can be initiated by anti-AQP4 autoantibody. First one was dependent on the complement cytotoxicity via C5b-C9 complex formation, and the second one was dependent on the reverse of astrocyte glutamate pomp into extracellular space on the C5a-preactivated neutrophils. As a consequence, part of the astrocytes was destroyed, however a certain population of astrocytes polarized into proinflammatory cells which characterized pathological glutamate removal from extracellular space.
Disclosure: This research was funded in part by grants from the National Science Centre (OPUS 2015/17/B/NZ6/04251 to P.L.; OPUS 2014/13/B/NZ6/00235 to P.L.); and the Medical University of Lodz (502-03/1-033-01/502-14-312 to P.P; 502-03/1-033-01/502-14-224 to M.D.).
Conflict of interest: The authors declare no competing financial interests
Paweł Piątek, Małgorzata Domowicz, Natalia Lewkowicz, Patrycja Przygodzka, Mariola Matysiak, Katarzyna Dzitko, Krzysztof W. Selmaj and Przemysław Lewkowicz: nothing to disclose.