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.

中文翻译：

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来自 Blighia welwitschii 的三萜糖苷及其在多发性硬化症中的抗体识别能力评价

多因素自身免疫性疾病中的多发性硬化症 (MS)，其中需要可靠的生物标志物进行治疗监测和诊断。自身抗体 (autoAbs) 是已知的生物标志物候选物，尽管它们在生物体液中的检测需要对其相关抗原进行全面表征。在过去的二十年里，一种旨在筛选假定自身抗原的反向化学方法强调了聚糖，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合成葡萄糖基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，以显着增加可以测试的聚糖的多样性。无患子科的三萜皂苷代表了最佳的起始材料，因为文献中对它们的大量描述揭示了基于葡萄糖的低聚糖的普遍存在。因此选择 Blighia welwitschii（无患子科）作为案例研究，分离并表征了十二种三萜皂苷。基于一维和二维核磁共振以及质谱法阐明了它们的结构，揭示了七种未描述的化合物。然后在酶联免疫吸附试验 (ELISA) 中测试了一系列具有各种寡糖部分的天然糖苷作为抗原，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存在相关性，允许确定与先前研究一致的构效关系。这种方法可能有助于识别推测参与 MS 发病机制的糖表位，但目前仍知之甚少。