IGE-MEDIATED ALLERGIC REACTION TO HYALURONIDASE IN PEDIATRIC ONCOLOGICAL PATIENTS

Hyaluronidase has been gaining increasing interest as a spreading fact or for better penetration of chemotherapeutics into CNS tumours. Five out of 16 patients with CNS tumours treated with hyaluronidase in addi tion to chemotherapeutic agents developed symptoms of immediate type a llergic reactions, therefore we sought to characterize the harmful all ergenic 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 h igh 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 specif ic IgE antibodies to the 73 and 41-43 kDa bands was found. Two patient s 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 sp ecific inhibition of IgE-binding to both bands was achieved after prei ncubation of the sera in four out of five patients with partially puri fied bovine hyaluronidase. Furthermore preincubation with gelatin, a s tabilising agent in the commercial extract, led to a partial inhibitio n in the sera of three patients. No specific IgE binding was detected either in the sera of atopic patients, or in the control group. Conclu sion IgE mediated allergic reactions to hyaluronidase may occur in pae diatric 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 specifie d, remains to be elucidated.