Sensitizing capacity of some trimers in p-tert-butylphenol-formaldehyde resin

Contact allergy to p-tert-butylphenol formaldehyde resin (PTBP-F-R) is not rare. This resin consists of a large number of substances, most of which are still unknown. For diagnostic and preventive reasons the chemical identity of the sensitizers should be known, as well as their sensitizing capacities, cross-reaction patterns and presence in the environment. The aims of this study were to investigate the sensitizing capacities and potential cross-reacting patterns for 4-tert-butyl- 2,6-bis-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-phenol (XIII), 4-tert-butyl-2- (5 - tert - butyl - 2 - hydroxy-benzyloxymethyl) - 6 - (5 - tert - butyl - 2 - hydroxy - 3 - hydroxymethyl-benzyloxy methyl)-phenol (XIVa) and 7,15,23-tri-tert-butyl-25,26,27-trihydroxy-2,3,10,11,18,19-hexahomo-3,11,19-trioxacalix(3)arene (XVIII) by the guinea pig maximization test. 4-tert-Butyl-2,6-bis-hydroxymethyl-phenol, 4-tert-butylbenzene-1,2-diol, 4-tert-butyl-2-hydroxymethyl-phenol, 4-tert-butyl-phenol, 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethyl-phenol, 4-tert-butyl-2-[5-tert-butyl-3-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl) - 2 -hydroxy-benzyloxymethyl] - 6 - (5 - tert-butyl- 2 -hydroxy- 3 -hydroxymethyl-benzyloxymethyl)- phenol and were used as potential cross-reacting substances. In this study it is strongly indicated that the linear trimer XIII has a sensitizing capacity in the guinea pig which was significant when compared to the controls (p = 0.024). No cross-reactions were detected in animals induced with the linear trimer XIII. The linear trimer XIVa and the cyclic trimer XVIII failed to induce sensitization.     

Assessment of contact allergen cross-reactivity by retesting

At former allergic contact dermatitis reaction sites retesting causes augmented hyper-reactivity, characterized by an accelerated onset within a few hours. This expression of 'local skin memory' has been ascribed to locally persisting allergen-specific effector/memory T cells. To verify this hypothesis, we investigated whether accelerated retest reactivity also occurs with cross-reactive allergens. Guinea pigs were immunized with either or both 2,4-dinitrochlorobenzene (DNCB) and 2-hydroxyethyl methacrylate (HEMA), and primary skin tests to these and cross-reactive methacrylic compounds were performed 12-21 days later. Subsequently, new skin tests were conducted 3 weeks later both at the former test ('retest') and contralateral, non-pretreated test ('control') sites, and skin test readings started 2 h later. Retest reactivity was evaluated by comparing retest and contralateral control reactions. Both contact sensitizers, HEMA and DNCB, induced strong retest reactivity, peaking at 4-6 h. Fully allergen-specific retest reactivity was observed when primary skin tests had been postponed until 21 days after immunization, most probably reflecting loss of accumulation of irrelevant allergen-primed T cells at that time. As hypothesized, retesting with various methacrylate congeners at primary HEMA, but not DNCB, skin test sites showed early hyperreactivity strengths in line with those observed earlier in conventional cross-reactivity studies. These results, therefore, support the view that local skin memory exhibits allergen specificity through residual allergen-primed T cells. Because the retesting procedure is readily applicable in clinical practice, it provides a tool not only for confirmation of doubtful contact allergic skin reactions, but also for distinguishing between true cross-reactivity and coincident multiple sensitization in man.     

Mustard allergy confirmed by double-blind placebo-controlled food challenges: clinical features and cross-reactivity with mugwort pollen and plant-derived foods

BACKGROUND: Mustard IgE-mediated allergy is supposed to be a rare cause of food allergy, and its clinical features and cross-reactivities have not been fully elucidated. METHODS: A prospective study was carried out, recruiting mustard allergic patients, and paired control subjects. A clinical questionnaire was administered, and skin-prick tests (SPT) with panels of aeroallergens and foods, serum extraction for in vitro tests and double-blind placebo-controlled food challenges (DBPCFC) were performed. RESULTS: Thirty-eight mainly adult patients, with 10.5% reporting systemic anaphylaxis, were included in the study [age (mean +/- SD): 21.9 +/- 8.6 years]. DBPCFC were performed in 24 patients, being positive in 14 cases (58.3%). Patients with positive outcome showed significantly greater mustard SPT than those with negative outcome (8.2 +/- 3.7 vs 5.3 +/- 2.4 mm, P <0.05), and the receiver-operating characteristic (ROC) curve analysis yielded a cut-off value for mustard commercial SPT of 8 mm, with a specificity of 90% (95% CI, 55.5-98.3), and a sensitivity of 50% (95% CI, 23.1-76.9). A significant association between mustard hypersensitivity and mugwort pollen sensitization was found (97.4% of patients), with partial cross-reactivity demonstrated by UniCAP System inhibition assays. All patients showed sensitization to other members of Brassicaceae family, and cross-reactivity among them was also confirmed. Moreover, significant associations with nut (97.4%), leguminous (94.7%), corn (78.9%), and Rosaceae fruit (89.5%) sensitizations were also shown. Around 40% of these food sensitizations were symptomatic, including food-dependent exercise-induced anaphylaxis in six patients. CONCLUSIONS: Mustard allergy is a not-uncommon disorder that can induce severe reactions. Significant associations with mugwort pollinosis and several plant-derived food allergies are demonstrated, suggesting a new mustard-mugwort allergy syndrome. A relationship between this syndrome and food-dependent exercise-induced anaphylaxis is also reported.     

Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin

A group of 34 penicillin-allergic patients was studied to determine skin test reactivity to the different penicillins involved in inducing the allergic reaction and the cross-reactivity with side-chain-related and side-chain-unrelated cephalosporins. All the subjects selected for the study had to be skin test positive to at least one of the following determinants: benzyl-penicilloyl-polylysine (BPO-PLL), minor-determinant mixture (MDM), amoxicillin (AX), or ampicillin (AMP), or to possess in vitro IgE to the following conjugates: benzyl-penicilloyl-human-serum albumin (BPO-HSA), ampicilloyl-human-serum albumin (AMP-HSA), and amoxicilloyl-human-serum albumin (AX-HSA). Cephalexin (CE) and ceftazidime (CEF) were used to assess cross-reactivity. If skin tests to any of these compounds were positive, the patient was considered to be allergic; if negative, a challenge test was performed. Sixteen patients (47%) were skin test positive to BPO and/or MDM, and nine (26%) exclusively to AX and/or AMP. In three cases (8%), the RAST was positive although the skin test was negative; one to BPO-HSA and two to AX-HSA and AMP-HSA. Six patients (17%) needed to be challenged with the penicillin involved to establish the diagnosis. In five patients (14%), the skin tests were positive to CE and in none to CEF. In all the others, the skin tests were negative to both cephalosporins, and the patients tolerated the drugs when challenged. These results indicate the relevance of side-chain-specific minor determinants in betalactams allergy and provide support for the role of this chemical structure in the evaluation of cross-reactivity between penicillins and cephalosporins.     

Computational tools for the study of allergens

Allergy is a major cause of morbidity worldwide. The number of characterized allergens and related information is increasing rapidly creating demands for advanced information storage, retrieval and analysis. Bioinformatics provides useful tools for analysing allergens and these are complementary to traditional laboratory techniques for the study of allergens. Specific applications include structural analysis of allergens, identification of B- and T-cell epitopes, assessment of allergenicity and cross-reactivity, and genome analysis. In this paper, the most important bioinformatic tools and methods with relevance to the study of allergy have been reviewed.     

Allergenic cross-reactivity of Curvularia lunata with other airborne fungal species

BACKGROUND: Curvularia lunata is an important fungus for respiratory allergic disorders. Previous studies indicated cross-reactivity of Curvularia with other fungi. However, the cross-reactive allergenic component (s) were not identified. The present work was carried out to study the shared allergenic components of C. lunata and others. METHODS: Cross-reactivity studies were performed using pooled hypersensitive patient sera to C. lunata by ELISA, immunoblot, immunoblot inhibition and ELISA inhibition. RESULTS: Many C. lunata sensitive patients showed positive skin test to five other fungi. Alternaria alternata exhibited maximum (68%) whereas Cladosporium herbarum showed the least (17%) skin reactivity. Immunoblots of fungal extracts with pooled sera showed common proteins. Fusarium solani and C. herbarum showed negligible IgE binding. IgE ELISA inhibition with C. lunata showed 92% inhibition whereas A. alternata and E. nigrum showed 84% and 63%, respectively. Immunoblot inhibition with self protein showed complete loss of IgE-binding activity. Proteins of 26, 31, 38, 45 and 50 kDa of C. lunata were inhibited by A. alternata and E. nigrum, whereas A. fumigatus inhibited 26, 45 and 50 kDa proteins. CONCLUSIONS: Significant allergenic cross-reactivity exists among proteins of C. lunata, A. alternata and E. nigrum. Proteins of 26, 31, 38, 45 and 50 kDa are shared allergens in these fungi.