Detection of high-molecular-weight amyloid serum protein complexes using biological on-line tracer sedimentation.
Detection of high-molecular-weight amyloid serum protein complexes using biological on-line tracer sedimentation.
复制标题
使用生物在线示踪沉降检测高分子量淀粉样血清蛋白复合物。
DOI：
10.1016/j.ab.2012.03.016
复制
发表时间：
2012
影响因子：
2.9
通讯作者：
Connors,LawreenH
中科院分区：
文献类型：
--
作者：
Kingsbury,JonathanS;Laue,ThomasM;Chase,SusanF;Connors,LawreenH
系统性淀粉样变性是一类罕见但致命的蛋白质折叠疾病，其诊断和治疗需求显著未得到满足。目前淀粉样蛋白进展的症状模型包括可溶性毒性聚集体以及纤维组织沉积物的致病作用。虽然许多研究集中在阐明聚集毒性的潜在机制，但支持其在体内存在的证据有限。我们报告使用一种技术，我们称之为生物在线示踪沉降（BOLTS），以检测异常高分子量复合物（HMWCs）的血清样本中的个体与系统性淀粉样变性由于聚集和沉积的野生型甲状腺素运载蛋白（老年性系统性淀粉样变性，SSA）或单克隆免疫球蛋白轻链（AL淀粉样变性）。在这项概念验证研究中，在77份淀粉样蛋白样本中的31份（40.3%）中观察到HMWC。在进行BOLTS分析的17个非淀粉样蛋白对照样品中均未检测到HMWC。这些发现支持存在潜在毒性的淀粉样蛋白聚集体，并表明BOLTS可能是一个有用的分析和诊断平台，在淀粉样变性或其他疾病的研究中，异常分子复合物在血清中形成。
The systemic amyloidoses are a rare but deadly class of protein folding disorders with significant unmet diagnostic and therapeutic needs. The current model for symptomatic amyloid progression includes a causative role for soluble toxic aggregates as well as for the fibrillar tissue deposits. Although much research is focused on elucidating the potential mechanism of aggregate toxicity, evidence to support their existence in vivo has been limited. We report the use of a technique we have termed biological on-line tracer sedimentation (BOLTS) to detect abnormal high-molecular-weight complexes (HMWCs) in serum samples from individuals with systemic amyloidosis due to aggregation and deposition of wild-type transthyretin (senile systemic amyloidosis, SSA) or monoclonal immunoglobulin light chain (AL amyloidosis). In this proof-of-concept study, HMWCs were observed in 31 of 77 amyloid samples (40.3%). HMWCs were not detected in any of the 17 nonamyloid control samples subjected to BOLTS analyses. These findings support the existence of potentially toxic amyloid aggregates and suggest that BOLTS may be a useful analytic and diagnostic platform in the study of the amyloidoses or other diseases where abnormal molecular complexes are formed in serum.