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纤维蛋白降解产物(FnDP)检测:血浆中标准化问题及靶抗原分析

Fibrin degradation product (FnDP) assays: analysis of standardization issues and target antigens in plasma.

作者信息

Gaffney P J, Edgell T, Creighton-Kempsford L J, Wheeler S, Tarelli E

机构信息

Division of Haematology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts.

出版信息

Br J Haematol. 1995 May;90(1):187-94. doi: 10.1111/j.1365-2141.1995.tb03399.x.

DOI:10.1111/j.1365-2141.1995.tb03399.x
PMID:7786784
Abstract

The in vivo formation of fibrin and its subsequent secondary fibrinolytic digestion yields a variety of crosslinked fibrin degradation products (XL/FnDP). One of these is known as D-dimer and a variety of ELISA-type commercial kits using monoclonal antibodies to D-dimer have been developed. We have investigated the possibility of establishing a standard such that these various kits might indicate the same levels of D-dimer in the same samples. We have concluded that because it seems that each individual monoclonal antibody to D-dimer targets a unique and distinct epitope in the FnDP fraction the notion of introducing a standard D-dimer which will respond uniformly to each D-dimer monoclonal antibody is not feasible. Using various monoclonal and polyclonal antibodies in conjunction with gel exclusion chromatography we have examined human plasma derived from patients with disseminated intravascular coagulation (DIC) which contained high levels of fibrin degradation products (FnDP). The data suggested that the FnDP fraction in plasma contained mostly high molecular weight (> 2 x 10(6) daltons) crosslinked fragments which contain high levels of fibrinopeptide A. Many of these crosslinked fragments crossreact with antibodies to D-dimer because they each contain D-dimer as a structural component. On the basis of this data, a novel sequence of events is proposed which may occur during the aggregation of fibrin in vivo.

摘要

纤维蛋白在体内形成及其随后的继发性纤维蛋白溶解消化产生多种交联纤维蛋白降解产物(XL/FnDP)。其中一种产物被称为D - 二聚体,并且已经开发出多种使用针对D - 二聚体的单克隆抗体的ELISA型商业试剂盒。我们研究了建立一种标准的可能性,以使这些不同的试剂盒在相同样本中能够显示相同水平的D - 二聚体。我们得出的结论是,由于似乎每种针对D - 二聚体的单克隆抗体都靶向FnDP组分中一个独特且不同的表位,所以引入一种能对每种D - 二聚体单克隆抗体产生一致反应的标准D - 二聚体的想法是不可行的。我们使用各种单克隆和多克隆抗体结合凝胶排阻色谱法,检测了来自患有弥散性血管内凝血(DIC)且含有高水平纤维蛋白降解产物(FnDP)患者的人血浆。数据表明,血浆中的FnDP组分主要包含高分子量(> 2×10⁶道尔顿)的交联片段,这些片段含有高水平的纤维蛋白肽A。许多这些交联片段与针对D - 二聚体的抗体发生交叉反应,因为它们各自都含有作为结构成分的D - 二聚体。基于这些数据,提出了一种在体内纤维蛋白聚集过程中可能发生的新的事件序列。

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