High incidence of anti-FVIII antibodies against non-coagulant epitopes in haemophilia A patients: A possible role for the half-life of transfused FVIII
High incidence of anti-FVIII antibodies against non-coagulant epitopes in haemophilia A patients: A possible role for the half-life of transfused FVIII
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DOI：
10.1046/j.1365-2141.1996.d01-1705.x
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发表时间：
1996-06-01
影响因子：
6.5
通讯作者：
Girolami, A
中科院分区：
文献类型：
--
作者：
Dazzi, F;Tison, T;Girolami, A
能够抑制因子VIII （FVIII）凝血活性的抗体（Abs）的出现是a型血友病的一个严重并发症，导致输注的FVIII活性受到抑制。目前尚不清楚输血后抗体是否或在多大程度上也可能针对非凝固性表位产生。因此，我们建立了一个理论上能够检测所有FVIII诱导抗体的系统，该系统基于将人重组FVIII涂覆在聚苯乙烯微滴板上的酶联免疫分类试验（ELISA）。分析了23例不同程度的A型血友病患者的血清样本（22例转至本中心，1例转至Bari中心）。虽然只有1例患者在Bethesda试验中呈阳性，但在39%的患者中检测到不同程度的抗体；输血FVIII被发现诱导抗体升升高，支持这种现象的特异性。在3例患者中评估了这些非抑制性抗体的临床相关性；虽然没有抗体或抗体含量低的患者的半衰期没有任何变化，但发现高滴度抗体患者的FVIII清除率增强。我们建议在常规评估A型血友病患者时采用ELISA检测抗fviii抗体。
The occurrence of antibodies (Abs) capable of inhibiting factor VIII (FVIII) coagulant activity is a severe complication in haemophilia A, leading to the inhibition of transfused FVIII activity. It is not known whether, or to what extent, post-transfusion antibodies may also arise against non-coagulant epitopes. Therefore we set up a system capable, in theory, to detect all the FVIII-induced antibodies by use of an enzyme-linked immunoassorbent assay (ELISA) based on coating human recombinant FVIII onto polystyrene microtitre plates. Serum samples from 23 patients affected by haemophilia A of different gravity (22 referred to our Centre and one to the Bari Centre) were analysed. Although only one patient was positive at Bethesda assay, the presence of antibodies in ELISA was detected in 39% of patients in variable degrees; transfusion with FVIII was found to induce a raise in antibody litre, arguing in favour of the specificity of the phenomenon. The clinical relevance of these non-inhibitory antibodies was evaluated in three patients; although half-life did not show any change in the patients without or with low amount of antibodies, FVIII clearance was found enhanced in the patient displaying high titre antibodies. We propose detection of anti-FVIII anti bodies by ELISA when routinely assessing haemophilia A patients.