Demonstration of heterodimeric fibrinogen molecules partially conjugated with albumin in a novel dysfibrinogen: Fibrinogen Mannheim V
Demonstration of heterodimeric fibrinogen molecules partially conjugated with albumin in a novel dysfibrinogen: Fibrinogen Mannheim V
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DOI：
10.1160/th08-09-0559
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发表时间：
2009-07-01
影响因子：
6.7
通讯作者：
Brennan, Stephen O.
中科院分区：
文献类型：
--
作者：
Dempfle, Carl-Erik;George, Peter M.;Brennan, Stephen O.
一名30岁的女性在怀孕早期经历了三次流产。广泛的实验室筛查显示，PT衍生性纤维蛋白原检测到的血浆纤维蛋白原水平较低，约为1g/L。免疫学测定的纤维蛋白原水平为3g/L。功能克劳斯试验的中间结果为1.78g/L。在她的第四次和第五次怀孕期间，患者接受了纤维蛋白原浓缩物(德国马尔堡的海默泰坦，CLS Behring)，从4克人纤维蛋白原开始，然后每隔一天2克，直到怀孕15周。这些怀孕的进一步过程是平安无事的。SDS-PAGE和免疫印迹显示高分子量纤维蛋白原(HMW)和低分子量纤维蛋白原(LMW)位置的双条带，单个LMW‘纤维蛋白原条带，以及与抗人血清白蛋白(HSA)抗血清反应的比HMW-Fbg更高分子量的额外条带。这些条带对应于与白蛋白结合的不同的纤维蛋白原。用多克隆抗纤维蛋白多肽A抗血清进行简化的SDS-PAGE和免疫印迹显示，增加了一条较低分子量的Aα链带。A基因第5外显子的扩增和测序表明，在密码子Aα494(C1537delA)上有一个新的单核苷酸缺失。His494被Pro取代，接着是23个新氨基酸(LMKLPSSTLPQLEKHSQVSSHLC)，然后在Cys517之后过早截断，产生一个游离的C-末端半胱氨酸，可能与白蛋白相连。这种新的纤维蛋白原突变导致了一系列平衡的同源和异源二聚体纤维蛋白原分子，其中一些分子与白蛋白结合。
A 30-year-old female experienced three miscarriages in early pregnancy. Extensive laboratory screening showed a low plasma fibrinogen level of approximately 1 g/l detected by PT-derived fibrinogen assay. The fibrinogen level in the immunological assay was 3 g/l. The functional Clauss assay yielded an intermediate result of 1.78 g/l. During her fourth and fifth pregnancy, the patient received fibrinogen concentrates (Haemocomplettan, CLS Behring, Marburg, Germany), starting with 4 grams of human fibrinogen,followed by 2 grams every second day until the 15(th) week of pregnancy. The further course of these pregnancies was uneventful. SDS-PAGE and immunoblotting showed doublet bands in the positions of the high-molecular weight (HMW)- and low-molecular-weight (LMW)-fibrinogen, a single LMW' fibrinogen band, plus additional bands with higher molecular weight than HMW-fibrinogen, which were also reactive with anti-human serum albumin (HSA) antiserum. These bands correspond to variant fibrinogen conjugated with albumin. Reduced SDS-PAGE and immunoblotting using polyclonal anti-fibrinopeptide A antiserum disclosed one additional A alpha-chain band with lower molecular weight. Amplification and sequencing of exon 5 of the a gene indicated heterozygosity for a novel single nucleotide deletion at codon A alpha 494 (C1537delA). His494 is replaced by Pro and this is followed by 23 (LMKLPSSTLPQLEKHSQVSSHLC) new amino acids before premature truncation after Cys517, yielding a free C-terminal cysteine, which may link with albumin. This new fibrinogen mutation, leads to a balanced array of homo- and heterodimeric fibrinogen molecules, some of which are conjugated to albumin.