Triterpene glycosides from Blighia welwitschii and evaluation of their antibody recognition capacity in multiple sclerosis.
- 作者列表："Petit B","Mitaine-Offer AC","Fernández FR","Papini AM","Delaude C","Miyamoto T","Tanaka C","Rovero P","Lacaille-Dubois MA
:Multiple sclerosis (MS) in a multifactorial autoimmune disease in which reliable biomarkers are needed for therapeutic monitoring and diagnosis. Autoantibodies (autoAbs) are known biomarker candidates although their detection in biological fluids requires a thorough characterization of their associated antigens. Over the past twenty years, a reverse chemical-based approach aiming to screen putative autoantigens has underlined the role of glycans, in particular glucose, in MS. Despite the progress achieved, a lack of consensus regarding the nature of innate antigens as well as difficulties proposing new synthetic glucose-based structures have proved to be obstacles. Here is proposed a strategy to extend the current methodology to the field of natural glycosides, in order to dramatically increase the diversity of glycans that could be tested. Triterpene saponins from the Sapindaceace family represent an optimal starting material as their abundant description in the literature has revealed a prevalence of glucose-based oligosaccharides. Blighia welwitschii (Sapindaceae) was thus selected as a case study and twelve triterpene saponins were isolated and characterized. Their structures were elucidated on the basis of 1D and 2D NMR as well as mass spectrometry, revealing seven undescribed compounds. A selection of natural glycosides exhibiting various oligosaccharide moieties were then tested as antigens in enzyme-linked immunosorbent assay (ELISA) to recognize IgM antibodies (Abs) in MS patients' sera. Immunoassay results indicated a correlation between the glycan structures and their antibody recognition capacity, allowing the determination of structure-activity relationships that were coherent with previous studies. This approach might help to identify sugar epitopes putatively involved in MS pathogenesis, which remains poorly understood.
: 多因素自身免疫性疾病中的多发性硬化 (MS)，其中需要可靠的生物标志物用于治疗监测和诊断。自身抗体 (autoab) 是已知的生物标志物候选物，尽管其在生物流体中的检测需要对其相关抗原进行彻底表征。在过去的二十年中，旨在筛选推定的自身抗原的基于反向化学的方法强调了聚糖，特别是葡萄糖在MS中的作用。尽管取得了进展，但关于先天抗原的性质缺乏共识以及提出新的基于合成葡萄糖的结构的困难已被证明是障碍。这里提出了一种将当前方法扩展到天然糖苷领域的策略，以便显著增加可以测试的聚糖的多样性。来自无患子家族的三萜皂苷代表了最佳的起始材料，因为它们在文献中的大量描述已经揭示了基于葡萄糖的寡糖的普遍存在。因此，选择blightia wellwitschii (Sapindaceae) 作为案例研究，并分离和表征了12个三萜皂苷。基于1D和2dnmr以及质谱来阐明它们的结构，揭示了7种未描述的化合物。然后在酶联免疫吸附测定 (ELISA) 中测试表现出各种寡糖部分的天然糖苷的选择作为抗原以识别MS患者血清中的IgM抗体 (Abs)。免疫测定结果表明聚糖结构与其抗体识别能力之间的相关性，允许确定与先前研究一致的结构-活性关系。这种方法可能有助于鉴定推测参与MS发病机制的糖表位，这仍然知之甚少。
METHODS:PURPOSE:The aim of the study was to assess dual-task cost to spatio-temporal gait parameters in people with multiple sclerosis and a matched control group. METHOD:The multiple sclerosis group was composed of 17 participants with a diagnosis of multiple sclerosis and an Expanded Disability Status Scale score of less than 6. A total of 17 healthy participants were allocated to the control group by stratification. Controls were matched on the basis of age, sex, sociocultural habits, and body structure. Dual-task cost was determined by within-group repeated-measures analysis of variance. Participants were instructed to ambulate under normal conditions and perform a discrimination and decision-making task concurrently. Then, between-group analysis of variance was used to assess differences in mean dual-task cost between groups and determine dual-task cost differential. Testing was performed using three-dimensional photogrammetry and an electronic walkway. RESULTS:Based on dual-task cost differential, gait cycle time increase (-5.8%) and gait speed decrease (6.3%) because of multiple sclerosis-induced impairment. CONCLUSIONS:During single- and dual-task conditions, gait speed was lower in multiple sclerosis participants, because of a shorter step length and increased swing time. Increased gait time might be the result of compensatory mechanisms adopted to maintain stability while walking specially during the double-support phases.
METHODS:OBJECTIVE:The aims of the study were to compare mobility in multiple sclerosis, Parkinson disease, and stroke, and to quantify the relationship between mobility and participation restrictions. DESIGN:This is a multicenter cross-sectional study. Included were compliant subjects with Parkinson disease, multiple sclerosis, and stroke seen for rehabilitation, with no comorbidities interfering with mobility. Functional scales were applied to each subject to investigate gait speed (10-meter walking test), balance while maintaining body position (Berg Balance Scale), dynamic balance and mobility (Timed Up and Go and Dynamic Gait Index), and participation (Community Integration Questionnaire). RESULTS:Two hundred ninety-nine patients (111 multiple sclerosis, 94 Parkinson disease, and 94 stroke) were enrolled. Stroke had the slowest gait speed (mean gait speed = 0.9 m/sec) compared with Parkinson disease (1.1 m/sec), and multiple sclerosis (1.2 m/sec) (P < 0.001). Multiple sclerosis was more limited than Parkinson disease and stroke in dynamic balance both in the Timed Up and Go Test (multiple sclerosis = 16.7 secs, Parkinson disease = 11.4 secs, stroke = 14.0 secs; P < 0.001) and Dynamic Gait Index (multiple sclerosis = 11.6 points, Parkinson disease = 12.9 points, stroke = 13.6 points; P = 0.03); ability to maintain balance and body position (Berg Balance Scale) was more affected in stroke and Parkinson disease than multiple sclerosis (multiple sclerosis = 42.6 points, Parkinson disease = 39.4 points, stroke = 39.7 points; P = 0.03). Balance disorders were associated with participation restrictions but not gait speed. CONCLUSIONS:Neurological conditions have differing impacts on gait and balance, leading to different levels of participation restriction.
METHODS:OBJECTIVES:Cerebrospinal fluid (CSF) and blood neurofilaments (NFLs) are markers of axonal damage and are being investigated, mostly in relapsing-remitting (RR) MS, as a marker of disease activity and of response to treatment, while there are less data in progressive MS patients. Primary aim was to measure NFL in plasma samples of untreated patients with primary (PP) and secondary (SP) progressive MS and to correlate them with disability, disease severity, and prior/subsequent disability progression. MATERIALS AND METHODS:Neurofilament concentrations were measured using SIMOA (Single Molecule Array, Simoa HD-1 Analyzer; Quanterix). RESULTS:Neurofilament concentrations were measured on plasma samples of 70 progressive (27 PP and 43 SP), 21 RRMS patients, and 10 HCs. Longitudinal plasma NFL (pNFL) concentrations (median interval between sampling: 25 months) were available for nine PP/SP patients. PNFL concentrations were significantly higher in PP/SP compared to RRMS patients. They correlated with EDSS and MS Severity Score values. There was no difference in pNFL levels between PP/SP patients with EDSS progression in the preceding year (14% of patients) or during a median follow-up of 27 months (41%). In the longitudinal sub-study, pNFL levels increased in all patients between sampling by a mean value of 23% while EDSS mostly remained stable (77% of cases). CONCLUSION:In PP/SP progressive MS patients, pNFL levels correlate with disability and increase over time, but are not associated with prior/subsequent disability progression, as measured by EDSS, which may not be a sufficiently sensitive tool in this context.