Further investigation of the prohapten concept: reactions to benzene derivatives in man

Abstract

p-Phenylenediamine (PPDA) is a strong contact sensitizer which is included in the standard patch test tray and which can also act as an indicator of allergy to related substances by virtue of cross-reactions. In a previous study, the pattern of cross-reactions between PPDA and related substances was investigated in the guinea pig to evaluate the prohapten concept. The results provided some support for this concept, but also indicated that a number of reactive intermediates might be behaving as haptens. This work has now been extended to an examination of the prohapten concept in man in PPDA-allergic subjects. These subjects were tested with 7 substituted benzenes, plus PPDA. Of these, the 1,4-substituted benzenes hydroquinone, Metol, PPDA and p-aminophenol are all capable theoretically of giving rise to benzoquinone by oxidation (after demethylation in the case of Metol). However, as had been the case in the guinea pig, only a limited degree of cross-reaction was observed. Only one of the subjects allergic to PPDA gave a clearly positive allergic reaction to benzoquinone. The data provided only limited support for the prohapten concept in terms of benzoquinone as the ultimate hapten for a range of 1,4-substituted benzenes. As indicated in the guinea pig, a range of reaction intermediates or indeed other oxidation products may be involved. So, for each molecule, the sensitizing activity and potential to give rise to cross-reactions may depend on the balance between routes of skin metabolism.

Polymorphisms in genes involved in innate immunity and susceptibility to benzene-induced hematotoxicity

“…Table 1. Association between selected genetic polymorphism and WBC counts in benzene-exposed workers and controls humans exposed to benzene oxidation products has also been described our findings are biologically plausible (Basketter and Liden, 1992).…”

Allergen‐induced changes in interleukin 1β (iL‐1β) mRNA expression by human blood‐derived dendritic cells: inter‐individual differences and relevance for sensitization testing

“…The ability of PPD to elicit comparatively robust increases in IL-1␤ mRNA in cells derived from responder donors is intriguing because this chemical is usually regarded as being a prohapten, requiring metabolic conversion to, for example, Bandrowski's Base (BB) for allergenic activity. 24 It is of interest that in an investigation of the ability of LCs to provoke primary T lymphocyte proliferative responses to chemical allergens in vitro, Krasteva et al 25 found that although the parent molecule (PPD) induced responses in only one of six experiments, BB routinely caused primary sensitization. On the basis of the data that we report here, it could be argued that PPD does have some intrinsic allergenic potential or, alternatively, that the culture system employed possesses some metabolic activity.…”

Reactivity of Contact Allergenic Haptens to Amino Acid Residues in a Model Carrier Peptide, and Characterization of Formed Peptide-Hapten Adducts¹

“…Other inducers of ACD, such as phenols and phenylenediamine derivatives [4], have to be activated by oxidation to yield reactive electrophilic intermediates before addition to proteins can occur [4,5]. No complete antigen has been chemically defined and the chemical reaction between the hapten and the carrier protein in vivo is unknown.…”

“…Activated intermediates of two inducers of ACD, 1,4-benzoquinone 2 and 4-t-butyl-1,2-benzoquinone 3 ( fig. 2) were chosen as model haptens [4,8] and the outcome of the reaction of these haptens with the model peptide under physiologic conditions was analyzed. The adducts were isolated and their structures determined by nuclear magnetic resonance (NMR) and mass spectrometry (MS).…”