Laidmäe Ivo, Belozjorova Jevgenia, Sawyer Evelyn S, Janmey Paul A, Uibo Raivo
Immunology Group, IGMP University of Tartu, Ravila Street 19, Tartu 50411, Estonia.
Biologicals. 2012 Jan;40(1):55-60. doi: 10.1016/j.biologicals.2011.12.008. Epub 2012 Jan 14.
Fibrin sealants and topical thrombin preparations are often used for haemostatic and sealing applications in clinical practice. Some of these preparations contain coagulation factors from bovine sources. To minimize the risk of infection and immunogenicity connected with mammalian blood products, proteins derived from the plasma of farmed Atlantic salmon have been considered as an alternative to these mammalian sources. The purpose of this study is to characterize the immunogenicity of salmon fibrin glue in an animal model focusing on crossreactivity of IgG antibodies to host endogenous counterparts. After two immunizations with salmon fibrin glue, rats developed antibodies of IgG and IgM type to both fibrin glue components. Weak crossreactivity to endogenous fibrinogen and thrombin was seen in a subset of rats after the second application of salmon proteins. Coagulation tests showed that salmon fibrin application has no effect on coagulation profiles in mammalian hosts, consistent with previous reports that found no evidence of significant crossreactivity with host proteins. These studies support the potential suitability of salmon fibrin glue for the development of preparations with clinical impact. Before human use can be considered, however, additional data about safety of this preparation in other animal models, including large animal studies, should be obtained.
纤维蛋白密封剂和局部凝血酶制剂在临床实践中常用于止血和密封应用。其中一些制剂含有牛源凝血因子。为了将与哺乳动物血液制品相关的感染和免疫原性风险降至最低,养殖大西洋鲑鱼血浆衍生的蛋白质已被视为这些哺乳动物来源的替代品。本研究的目的是在动物模型中表征鲑鱼纤维蛋白胶的免疫原性,重点关注IgG抗体与宿主内源性对应物的交叉反应性。用鲑鱼纤维蛋白胶进行两次免疫后,大鼠产生了针对两种纤维蛋白胶成分的IgG和IgM型抗体。在第二次应用鲑鱼蛋白后,一部分大鼠出现了与内源性纤维蛋白原和凝血酶的弱交叉反应性。凝血试验表明,鲑鱼纤维蛋白的应用对哺乳动物宿主的凝血谱没有影响,这与之前的报道一致,即没有发现与宿主蛋白有显著交叉反应性的证据。这些研究支持了鲑鱼纤维蛋白胶在开发具有临床影响的制剂方面的潜在适用性。然而,在考虑用于人类之前,应该获得关于该制剂在其他动物模型(包括大型动物研究)中的安全性的更多数据。