IgE-mediated allergic reaction to hyaluronidase in paediatric oncological patients

Abstract

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.

Conclusion: 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.