Protein spectrum changes in exosomes after therapeutic plasma exchange in patients with neuromyelitis optica.
- 作者列表："Ma C","Wang S","Wang G","Wu Y","Yang T","Shen W","Zhuang Y","Zhang L","Liu X","Yang L","Feng Y","Yu Y","Liu Z","Wang D
INTRODUCTION:Neuromyelitis optica (NMO) is an autoimmune disease with a high rate of blindness and positive for the detection of aquaporin-4 antibody (AQP4) in most patients. NMO acute attacks are managed by high-doses of intravenous methylprednisolone followed by oral taper, and if symptoms fail to resolve, therapeutic plasma exchange (TPE) is added. TPE can remove pathological antibodies and inflammatory factors leading to clinical improvement. METHODS:A total of 40 TPE fluid collections from the first to fifth TPE treatments were obtained from eight patients. Exosomes were isolated by ultracentrifugation. Mass spectrometry analyses were used to compare protein change in TPE fluid collection exosomes after the first to the fifth TPE treatments in these patients. RESULTS:We detected 647 exosome proteins through data-independent acquisition analysis. It was found that some unknown functional antibody fragments and complement pathway proteins decreased after TPE treatment. The results revealed a significant involvement of the following two key pathways: the primary immunodeficiency and systemic lupus erythematosus that may be associated with NMO pathophysiology and TPE treatment efficacy (P < .05). A series of complement proteins may contribute to NMO; in addition, the following proteins increased with plasma exchange: complement factor H-related protein 5, bridging integrator 2, neuroplastin, pigment epithelium-derived factor, ficolin-1, extracellular matrix protein 1, and fatty acid-binding protein 5. CONCLUSION:Our study may provide a new perspective on the pathogenesis and treatment efficacy of NMO.
导读: 视神经脊髓炎 (NMO) 是一种致盲率较高的自身免疫性疾病，多数患者 aquaporin-4 抗体 (AQP4) 检测阳性。NMO 急性发作通过大剂量静脉注射甲基强的松龙后口服锥形治疗，如果症状未能缓解，加用治疗性血浆置换 (TPE)。TPE 可清除导致临床好转的病理抗体和炎症因子。 方法: 从 8 例患者中获得了第一至第五次 TPE 治疗的共 40 次 TPE 液体收集。通过超速离心法分离外泌体。使用质谱分析比较这些患者首次至第五次 TPE 治疗后 TPE 液体收集外泌体的蛋白变化。 结果: 我们通过数据非依赖性采集分析检测到 647 个外泌体蛋白。发现 TPE 处理后部分未知功能抗体片段和补体通路蛋白减少。结果发现以下两个关键通路显著参与: 原发性免疫缺陷和系统性红斑狼疮，可能与 NMO 病理生理和 TPE 治疗疗效相关 (p <.05)。一系列补体蛋白可能有助于 NMO; 此外，以下蛋白随着血浆置换而增加: 补体因子 H 相关蛋白 5 、桥接整合蛋白 2 、神经质体素 、色素上皮衍生因子、 ficolin-1 、细胞外基质蛋白 1 和脂肪酸结合蛋白 5。 结论: 我们的研究可能为 NMO 的发病机制和治疗疗效提供新的视角。
METHODS:Objective To clarify the existence of monophasic neuromyelitis optica spectrum disorders (NMOSD) and to identify predictive factors of long-term relapse-free form. Methods We retrospectively analyzed 289 Chinese patients with NMOSD. Selected subjects were divided into three groups based on the time interval between disease onset and the first relapse, if any. Clinical and imaging data were acquired from each patient’s medical record and evaluated as predictive factors for NMOSD. Results In total, none of the participating patients exhibited a monophasic form of NMOSD. Rather, 241 patients were selected for relapse tendency analysis; 143 (59.3%) patients relapsed within the first year, 66 (27.4%) during 1–5 years, and 32 (13.3%) beyond 5 years. Such onset symptoms as optic neuritis (ON) and non-longitudinally extensive transverse myelitis (LETM) were independent prognostic factors for a prolonged remission interval.
METHODS::Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.
METHODS:Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005−2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.