Szépfalusi Z, Nentwich I, Dobner M, Pillwein K, Urbanek R
Department of Paediatrics, University of Vienna-AKH, Austria.
Eur J Pediatr. 1997 Mar;156(3):199-203. doi: 10.1007/s004310050582.
Hyaluronidase has been gaining increasing interest as a spreading factor for better penetration of chemotherapeutics into CNS tumours. Five out of 16 patients with CNS tumours treated with hyaluronidase in addition to chemotherapeutic agents developed symptoms of immediate type allergic reactions, therefore we sought to characterize the harmful allergenic proteins of the bovine testes hyaluronidase enzyme preparation (Neopermease). The role of specific IgE for the allergic reaction was investigated. Using an immunoblotting technique, we investigated sera from 16 children treated with Neopermease (5 of them having developed anaphylactic reactions), 5 patients with atopy (atopic eczema) with high total IgE levels and 4 healthy children. SDS-PAGE of hyaluronidase preparation Neopermease revealed two major bands at 73 and 41-43 kDa. In all 5 sera from patients with adverse reactions, binding of specific IgE antibodies to have 73 and 41-43 kDa bands was found. Two patients reacted with the 73 kDa band exclusively, two patients reacted with both bands, one patient displayed IgE only to the 41-43 kDa band. A specific inhibition of IgE-binding to both bands was achieved after preincubation of the sera in four out of five patients with partially purified bovine hyaluronidase. Furthermore preincubation with gelatin, a stabilising agent in the commercial extract, led to a partial inhibition in the sera of three patients. No specific IgE binding was detected either in the sera of atopic patients, or in the control group.
IgE mediated allergic reactions to hyaluronidase may occur in paediatric oncological patients treated with hyaluronidase. Whether these children are sensitized by intravenous hyaluronidase treatment or by cross-reactivity of other preformed IgE antibodies, yet to be specified, remains to be elucidated.
透明质酸酶作为一种扩散因子，可使化疗药物更好地渗透到中枢神经系统肿瘤中，因此越来越受到关注。16例接受中枢神经系统肿瘤治疗的患者在使用化疗药物的同时加用了透明质酸酶，其中5例出现了速发型过敏反应症状，因此我们试图鉴定牛睾丸透明质酸酶制剂（Neopermease）中的有害过敏原蛋白。研究了特异性IgE在过敏反应中的作用。我们采用免疫印迹技术，检测了16例接受Neopermease治疗的儿童（其中5例发生过敏反应）、5例总IgE水平较高的特应性患者（特应性皮炎）以及4例健康儿童的血清。透明质酸酶制剂Neopermease的SDS-PAGE显示在73 kDa和41 - 43 kDa处有两条主要条带。在所有5例出现不良反应患者的血清中，均发现特异性IgE抗体与73 kDa和41 - 43 kDa条带结合。2例患者仅与73 kDa条带反应，2例患者与两条带均反应，1例患者仅对41 - 43 kDa条带显示IgE反应。5例患者中有4例的血清在与部分纯化的牛透明质酸酶预孵育后，对两条带的IgE结合均得到特异性抑制。此外，与商业提取物中的稳定剂明胶预孵育，导致3例患者血清中的结合部分受到抑制。在特应性患者血清或对照组中均未检测到特异性IgE结合。
接受透明质酸酶治疗的儿科肿瘤患者可能发生IgE介导的对透明质酸酶的过敏反应。这些儿童是通过静脉注射透明质酸酶治疗致敏，还是通过其他预先形成的IgE抗体的交叉反应致敏，尚待明确，仍有待阐明。
