Abstract：
UNASSIGNED: Genotyping and amyloid fibril detection in tissues are generally considered the diagnostic gold standard in transthyretin-related amyloidosis. Patients carry less stable TTR homotetramers prone to dissociation into non-native monomers, which rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Thus, the initial event of the amyloid cascade produces the smallest transthyretin species: the monomers. This creates engineering opportunities for diagnosis that remain unexplored.
UNASSIGNED: We hypothesise that molecular sieving represents a promising method for isolating and concentrating trace TTR monomers from the tetramers present in plasma samples. Subsequently, immunodetection can be utilised to distinguish monomeric TTR from other low molecular weight proteins within the adsorbed fraction. A two-step assay was devised (ImmunoSieve assay), combining molecular sieving and immunodetection for sensing monomeric transthyretin. This assay was employed to analyse plasma microsamples from 10 individuals, including 5 pre-symptomatic carriers of TTR-V30M, the most prevalent amyloidosis-associated TTR variant worldwide, and 5 healthy controls.
UNASSIGNED: The ImmunoSieve assay enable sensitive detection of monomeric transthyretin in plasma microsamples. Moreover, the circulating monomeric TTR levels were significantly higher in carriers of amyloidogenic TTR mutation.
UNASSIGNED: Monomeric TTR can function as a biomarker for evaluating disease progression and assessing responses to therapies targeted at stabilising native TTR.
UNASSIGNED: We hypothesise that molecular sieving represents a promising method for isolating and concentrating trace TTR monomers from the tetramers present in plasma samples. Subsequently, immunodetection can be utilised to distinguish monomeric TTR from other low molecular weight proteins within the adsorbed fraction. A two-step assay was devised (ImmunoSieve assay), combining molecular sieving and immunodetection for sensing monomeric transthyretin. This assay was employed to analyse plasma microsamples from 10 individuals, including 5 pre-symptomatic carriers of TTR-V30M, the most prevalent amyloidosis-associated TTR variant worldwide, and 5 healthy controls.
UNASSIGNED: The ImmunoSieve assay enable sensitive detection of monomeric transthyretin in plasma microsamples. Moreover, the circulating monomeric TTR levels were significantly higher in carriers of amyloidogenic TTR mutation.
UNASSIGNED: Monomeric TTR can function as a biomarker for evaluating disease progression and assessing responses to therapies targeted at stabilising native TTR.
摘要：
组织中的基因分型和淀粉样原纤维检测通常被认为是甲状腺素运载蛋白相关淀粉样变性的诊断金标准。患者携带不太稳定的TTR同源四聚体，容易解离成非天然单体，快速自组装成低聚物，最终,淀粉样纤维.因此，淀粉样蛋白级联的初始事件产生最小的转甲状腺素蛋白种类：单体。这创造了仍未探索的诊断工程机会。
■我们假设分子筛代表了一种有前途的方法，用于从血浆样品中存在的四聚体中分离和浓缩痕量TTR单体。随后，免疫检测可用于将单体TTR与吸附部分内的其他低分子量蛋白质区分开。设计了两步法(免疫测定法)，结合分子筛分和免疫检测来感知单体转甲状腺素蛋白。该测定法用于分析来自10个人的血浆微样品，包括5名症状前的TTR-V30M携带者，全球最普遍的淀粉样变性相关TTR变异，5健康对照
■Immunosive分析能够灵敏地检测血浆微样品中的单体转甲状腺素蛋白。此外，在淀粉样变性TTR突变的携带者中,循环单体TTR水平显著较高.
单体TTR可以作为生物标志物用于评估疾病进展和评估对靶向稳定天然TTR的治疗的反应。
■我们假设分子筛代表了一种有前途的方法，用于从血浆样品中存在的四聚体中分离和浓缩痕量TTR单体。随后，免疫检测可用于将单体TTR与吸附部分内的其他低分子量蛋白质区分开。设计了两步法(免疫测定法)，结合分子筛分和免疫检测来感知单体转甲状腺素蛋白。该测定法用于分析来自10个人的血浆微样品，包括5名症状前的TTR-V30M携带者，全球最普遍的淀粉样变性相关TTR变异，5健康对照
■Immunosive分析能够灵敏地检测血浆微样品中的单体转甲状腺素蛋白。此外，在淀粉样变性TTR突变的携带者中,循环单体TTR水平显著较高.
单体TTR可以作为生物标志物用于评估疾病进展和评估对靶向稳定天然TTR的治疗的反应。
