A novel quantitative hemolytic assay coupled with restriction fragment length polymorphisms analysis enabled early diagnosis of atypical hemolytic uremic syndrome and identified unique predisposing mutations in Japan.
A novel quantitative hemolytic assay coupled with restriction fragment length polymorphisms analysis enabled early diagnosis of atypical hemolytic uremic syndrome and identified unique predisposing mutations in Japan.
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DOI：
10.1371/journal.pone.0124655
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fujimura Y
中科院分区：
文献类型：
--
作者：
Yoshida Y;Miyata T;Matsumoto M;Shirotani-Ikejima H;Uchida Y;Ohyama Y;Kokubo T;Fujimura Y
对于血栓性微血管病（TMA），非典型溶血性尿毒综合征（阿胡斯）的诊断是通过排除产滋贺毒素大肠杆菌（STEC）相关的HUS和ADAMTS 13活性缺陷型血栓性血小板减少性紫癜（TTP）来进行的，通常使用继发性TMA的排除标准。如今，ADAMTS 13活性的测定和STEC感染的评估可以在几个小时内进行。然而，阿胡斯的可靠诊断通常需要对替代补体激活途径进行全面的基因分析，这通常需要至少几周的时间。然而，仅在大约70%的阿胡斯中鉴定出易患遗传异常。为了便于补体介导的阿胡斯的诊断，我们描述了一种定量溶血试验，使用绵羊红细胞（RBC）和人柠檬酸盐血浆，加标或不加新型抑制性抗补体因子H（CFH）单克隆抗体。在日本的45例阿胡斯患者中，24%（11/45）有中度至重度（≥50%）溶血，而其余76%（34/45）患者有轻度或无溶血（<50%）。前一组主要归因于CFH相关异常，后一组具有C3-p.I1157T突变（16/34），其通过限制性片段长度多态性（RFLP）分析鉴定。因此，定量溶血测定结合RFLP分析使得在日本60%（27/45）的患者在出现一周内能够早期诊断补体介导的阿胡斯。我们假设这种新型的定量溶血测定法在高加索人群中更有用，他们的CFH突变比例可能比日本患者更高。
For thrombotic microangiopathies (TMAs), the diagnosis of atypical hemolytic uremic syndrome (aHUS) is made by ruling out Shiga toxin-producing Escherichia coli (STEC)-associated HUS and ADAMTS13 activity-deficient thrombotic thrombocytopenic purpura (TTP), often using the exclusion criteria for secondary TMAs. Nowadays, assays for ADAMTS13 activity and evaluation for STEC infection can be performed within a few hours. However, a confident diagnosis of aHUS often requires comprehensive gene analysis of the alternative complement activation pathway, which usually takes at least several weeks. However, predisposing genetic abnormalities are only identified in approximately 70% of aHUS. To facilitate the diagnosis of complement-mediated aHUS, we describe a quantitative hemolytic assay using sheep red blood cells (RBCs) and human citrated plasma, spiked with or without a novel inhibitory anti-complement factor H (CFH) monoclonal antibody. Among 45 aHUS patients in Japan, 24% (11/45) had moderate-to-severe (≥50%) hemolysis, whereas the remaining 76% (34/45) patients had mild or no hemolysis (<50%). The former group is largely attributed to CFH-related abnormalities, and the latter group has C3-p.I1157T mutations (16/34), which were identified by restriction fragment length polymorphism (RFLP) analysis. Thus, a quantitative hemolytic assay coupled with RFLP analysis enabled the early diagnosis of complement-mediated aHUS in 60% (27/45) of patients in Japan within a week of presentation. We hypothesize that this novel quantitative hemolytic assay would be more useful in a Caucasian population, who may have a higher proportion of CFH mutations than Japanese patients.
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影响因子：
3.7
作者：
Loirat C;Frémeaux-Bacchi V
通讯作者：
Frémeaux-Bacchi V
影响因子：
20.3
作者：
Jozsi, Mihaly;Strobel, Stefanie;Zipfel, Peter F.
通讯作者：
Zipfel, Peter F.
DOI：
10.1073/pnas.1017087108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Kajander, Tommi;Lehtinen, Markus J.;Jokiranta, T. Sakari
通讯作者：
Jokiranta, T. Sakari
影响因子：
48
作者：
Li, Mamie Z.;Elledge, Stephen J.
通讯作者：
Elledge, Stephen J.
影响因子：
30.8
作者：
Lemaire, Mathieu;Fremeaux-Bacchi, Veronique;Schaefer, Franz;Choi, Murim;Tang, Wai Ho;Le Quintrec, Moglie;Fakhouri, Fadi;Taque, Sophie;Nobili, Franois;Martinez, Frank;Ji, Weizhen;Overton, John D.;Mane, Shrikant M.;Nuernberg, Gudrun;Altmueller, Janine;Thiele, Holger;Morin, Denis;Deschenes, Georges;Baudouin, Veronique;Llanas, Brigitte;Collard, Laure;Majid, Mohammed A.;Simkova, Eva;Nuernberg, Peter;Rioux-Leclercq, Nathalie;Moeckel, Gilbert W.;Gubler, Marie Claire;Hwa, John;Loirat, Chantal;Lifton, Richard P.
通讯作者：
Lifton, Richard P.