Annals of clinical and translational neurology · 2019
GRP 78 antibodies are associated with clinical phenotype in neuromyelitis optica.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shimizu Fumitaka, Takeshita Yukio, Hamamoto Yuka, Nishihara Hideaki, Sano Yasuteru, Honda Masaya, Sato Ryota, Maeda Toshihiko, Takahashi Toshiyuki, Fujikawa Susumu, Kanda Takashi
Аннотация
BACKGROUND: We previously reported the association between blood-brain barrier (BBB) dysfunction and glucose-regulated protein 78 (GRP 78) autoantibodies in neuromyelitis optica (NMO).
OBJECTIVE: We clarify whether the BBB-endothelial cell activation induced by immunoglobulin G (IgG) is associated with the clinical phenotype, disease activity, and markers of BBB disruption.
METHODS: We purified serum IgG from 24 serum samples from patients with NMO spectrum disorder (NMOSD), who were positive for anti-AQP4 antibodies (longitudinally extensive transverse myelitis [LETM], n = 14; optic neuritis [ON], n = 6; other phenotype, n = 4) and nine healthy controls. IgG was exposed to human brain microvascular endothelial cells (TY10) and the number of nuclear NF-κB p65-positive cells, as a marker of endothelial cell activation, was analyzed using a high-content imaging system. Change in BBB permeability was also measured. The presence of GRP78 autoantibodies was detected by Western blotting.
RESULTS: In the LETM group, IgG significantly induced the nuclear translocation of NF-κB p65 in comparison to the ON and healthy control groups. A significant correlation was observed between the number of NF-κB nuclear-positive cells and clinical markers of BBB disruption, including Gd enhancement in spinal MRI and the cerebrospinal fluid/serum albumin ratio. This effect was significantly reduced at the remission phase in the individual NMOSD patients. Furthermore, GRP78 antibody positivity was associated with the LETM phenotype and disease severity in NMOSD patients.
CONCLUSION: Endothelial cell activation was associated with the LETM phenotype, clinical markers of BBB disruption and disease activity. These observations may explain the phenotypic differences between the NMOSD subtypes, LETM, and isolated ON.
OBJECTIVE: We clarify whether the BBB-endothelial cell activation induced by immunoglobulin G (IgG) is associated with the clinical phenotype, disease activity, and markers of BBB disruption.
METHODS: We purified serum IgG from 24 serum samples from patients with NMO spectrum disorder (NMOSD), who were positive for anti-AQP4 antibodies (longitudinally extensive transverse myelitis [LETM], n = 14; optic neuritis [ON], n = 6; other phenotype, n = 4) and nine healthy controls. IgG was exposed to human brain microvascular endothelial cells (TY10) and the number of nuclear NF-κB p65-positive cells, as a marker of endothelial cell activation, was analyzed using a high-content imaging system. Change in BBB permeability was also measured. The presence of GRP78 autoantibodies was detected by Western blotting.
RESULTS: In the LETM group, IgG significantly induced the nuclear translocation of NF-κB p65 in comparison to the ON and healthy control groups. A significant correlation was observed between the number of NF-κB nuclear-positive cells and clinical markers of BBB disruption, including Gd enhancement in spinal MRI and the cerebrospinal fluid/serum albumin ratio. This effect was significantly reduced at the remission phase in the individual NMOSD patients. Furthermore, GRP78 antibody positivity was associated with the LETM phenotype and disease severity in NMOSD patients.
CONCLUSION: Endothelial cell activation was associated with the LETM phenotype, clinical markers of BBB disruption and disease activity. These observations may explain the phenotypic differences between the NMOSD subtypes, LETM, and isolated ON.