Detection of all anti-factor VIII antibodies in haemophilia A patients by the Bethesda assay and a more sensitive immunoprecipitation assay
Detection of all anti-factor VIII antibodies in haemophilia A patients by the Bethesda assay and a more sensitive immunoprecipitation assay
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DOI：
10.1046/j.1365-2516.2001.00456.x
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发表时间：
2001-01-01
期刊：
影响因子：
3.9
通讯作者：
Scandella, D
中科院分区：
文献类型：
--
作者：
Klinge, J;Auerswald, G;Scandella, D
来自40名血友病A患者的血浆被纳入德国血栓和止血学会儿科组的一项研究，通过Bethesda试验检测抑制剂抗体，并通过更敏感的免疫沉淀试验（IP）检测所有抗因子VIII抗体。在26例重度、11例中度和3例轻度血友病患者中，分别有18例、2例和1例经多次因子VIII输注后Bethesda效价呈阳性。在275例Bethesda滴度为0、0.6-1.0、> 1-5和> 5-655的血浆中，IP应答分别为0-238、0-61、0-786和43-6141，可靠的IP阳性滴度为> 4.2。IP滴度的重叠范围表明个体血浆中抑制性抗体与非抑制性抗体的比例有很大差异。在7例Bethesda滴度为0.6-1的患者中，有5例患者的IP滴度< 4.2，表明Bethesda滴度1缺乏准确性。在Bethesda检测阳性之前，只有3例患者通过IP检测发现了原发性免疫反应。这就妨碍了对哪些患者会有免疫反应的早期、可靠的检测。在4例接受免疫耐受治疗的患者中，在没有Bethesda滴度的情况下，IP检测仍然可以检测到抗因子VIII抗体，这表明抗体在所有患者中都没有被完全根除。我们的研究结果表明，使用Bethesda和IP检测可以更准确地检测所有患者的抗因子VIII抗体。
Plasmas from 40 haemophilia A patients enrolled in a study by the paediatric group of the German Society on Thrombosis and Hemostasis were tested by the Bethesda assay for inhibitor antibodies and by a more sensitive immunoprecipitation assay (IP) for all antifactor VIII antibodies. Of the 26 severe, 11 moderate and three mild haemophiliacs, 18, two, and none, respectively, had positive Bethesda titres after several factor VIII infusions. In 275 plasmas with Bethesda titres of 0, 0.6-1.0, > 1-5, and > 5-655, the IP responses were 0-238, 0-61, 0-786, and 43-6141, respectively, and a reliable positive IP titre was > 4.2. The overlapping ranges of IP titres indicated large differences in the ratio of inhibitory to noninhibitory antibodies in individual plasmas. In five of seven patients with Bethesda titres of 0.6-1, the IP titres were < 4.2, suggesting a lack of precision of Bethesda titres 1. Detection of the primary immune response was found in only three patients by IP assay before a positive Bethesda assay. This precludes early, reliable testing of which patients will be immunologically responsive. In four patients undergoing immune tolerance therapy, antifactor VIII antibodies were still detectable by the IP assay in the absence of a Bethesda titre, which indicates that antibodies were completely eradicated in none of the patients. Our results show that the use of both the Bethesda and IP assays can provide more accurate detection of antifactor VIII antibodies in all patients.