Hydroperoxides form specific antigens in contact allergy

Concomitant positive reactions to colophonium, oxidized limonene, and/or oxidized linalool are recorded in patch test studies. The main allergens in these patch test mixtures are hydroperoxides, which form antigens by a radical pathway. Theoretically, concomitant reactions can be explained not only by concomitant sensitization or by true cross-reactions but also by the hydroperoxides acting as oxidizing agents on skin proteins to form non-specific antigens without hapten-protein binding. The aim of this study was to explore concomitant reactions and cross-reactivity patterns among hydroperoxide haptens. We investigated whether individuals allergic to the main allergen in colophonium, 15-hydroperoxyabietic acid, would also react to limonene hydroperoxide or linalool hydroperoxide. Only 1 of 29 individuals reacted to more than 1 hydroperoxide. The cross-reactivity pattern among cumene hydroperoxide, limonene hydroperoxide, 1-(1-hydroperoxy-1-methylethyl) cyclohexene (cyclohexene hydroperoxide), and 15-hydroperoxydehydroabietic acid was investigated in guinea-pigs. No general cross-reactivity was observed. Cross-reactions between cumene hydroperoxide and cyclohexene hydroperoxide show that similarity in the overall structure and the way of antigen formation are needed. Quantum calculations were used to determine the formation energies of the intermediary radicals. We concluded that hydroperoxides form specific antigens and that formation of non-specific antigens is unlikely. The concomitant patch test reactions described in the literature are best explained as a result of multiple sensitizations.