CROSS-REACTIVITY PATTERNS OF CONTACT-SENSITIZING METHACRYLATES

Methacrylates are well-known contact sensitizers with increasing frequ ency of contact leading to occupational skin disease. Here, we develop ed an animal model to facilitate studies on the sensitizing capacities and cross-reactivity patterns between four clinically most important allergens: methyl methacrylate (MMA), 2-hydroxyethyl methacrylate (2-H EMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimetha crylate (EGDMA). Inbred guinea pigs were immunized by ic injections of 300 mu l of 1.0 M methacrylate solutions in Freund's complete adjuvan t into both Ranks, both ears, and the neck. After 14 days open skin te sts were performed with 50% MMA, 2-HEMA, or 2-HPMA or 10% EGDMA soluti ons in 40% DMSO in ethanol. Cross-reactivities were investigated 14 da ys later by skin testing with all four methacrylates. Using this newly developed protocol, strongly positive skin tests for methacrylates co uld be induced in almost all guinea pigs (MMA 26/26, 2-HEMA 16/18, 2-H PMA 15/16 and EGDMA 11/11). Whereas EGDMA induced only weak or infrequ ent cross-reactivities, 2-HEMA sensitization led to strong cross-react ions to all other methacrylates. Both MMA and 2-HPMA induced strong cr oss-reactivity to EGDMA but only weak to moderate reactivities to the Ether methacrylates. The absence of strong cross-reactions with monome thacrylates in EGDMA (dimethacrylate)sensitized animals may be explain ed by the predominance of highly EGDMA-specific T-cells in these anima ls. In contrast, sensitization with MMA, 2-HEMA, and 2-HPMA would lead to recruitment of T-cells cross-reactive to the other monomethacrylat es, according to their molecular similarities. The strong skin hyperse nsitivities observed for EGDMA in these latter groups are ascribed to enzymatic degradation into monomethacrylate compounds, notably 2-HEMA, at a rate sufficient to elicit cognate effector T-cells. The results of this study offer new insights in the development of methacrylate hy persensitivities and common cross-sensitization patterns in clinical p ractice. (C) 1998 Academic Press.