A critical assessment of allergen component-based in vitro diagnosis in cherry allergy across Europe

BACKGROUND: Food allergy to cherry occurs throughout Europe, typically with restricted oral reactions in the central and northern parts but with frequent systemic reactions in the Mediterranean region. Previous studies have demonstrated insufficient sensitivity of commercially available cherry extract reagents in the diagnosis of cherry allergy. OBJECTIVE: To assess the diagnostic performance of specific IgE tests based on recombinant cherry allergens in comparison with an extract-based assay and to skin prick test (SPT). A secondary objective was to analyse the frequency of systemic reactions in cherry-allergic subjects across Europe, including the largest population of LTP-sensitized subjects from central Europe studied to date. METHODS: A total of 186 subjects from central Europe and Spain were studied. Serum IgE was analysed with ImmunoCAP tests carrying rPru av 1, 3 and 4, combined and separately, and cherry extract. RESULTS: Among the central European cherry allergics, the mix of rPru av 1, 3 and 4 had a sensitivity of 95%, compared with 65% for cherry extract, and the IgE binding capacity of the recombinant mix was considerably higher. The sensitivity of the two tests was more comparable in the Spanish population, 95% and 86%, respectively. The recombinant allergen ImmunoCAP equalled SPT in terms of sensitivity and specificity. Consistent with previous reports, major geographic differences in sensitization pattern and prevalence of systemic reactions were found. A significantly higher rate of systemic reactions was found in Spanish patients sensitized to Pru av 3 whereas German patients sensitized to LTP only had oral allergy syndrome. CONCLUSIONS: The recombinant cherry allergen ImmunoCAP is a highly sensitive diagnostic tool, clearly superior to any diagnostic method based on cherry extract. Three cherry allergens are sufficient for detecting sensitization in 95% of cherry-allergic subjects. Systemic reactions are common in LTP-sensitized individuals but seem to require at least one additional causative factor.     

Food allergy and non-allergic food hypersensitivity in children and adolescents

BACKGROUND: Previous studies have shown a 10-fold discrepancy of self-reported food-induced symptoms and physician-diagnosed food hypersensitivity. Little information is available on the prevalence of food hypersensitivity in unselected paediatric populations. No data were available for German children. OBJECTIVE: To study the perception of food-induced symptoms in the paediatric population, to investigate the allergens accused, to objectify patients' reports, and to identify subgroups at risk of having food-induced allergy (FA) or non-allergic food hypersensitivity (NAFH) reactions. METHODS: This paper presents the data of the paediatric group (0-17 years) of a representative, randomly sampled, cross-sectional population-based survey studying 13 300 inhabitants of the German capital city Berlin regarding food-related symptoms. Instruments included mailed questionnaires, structured telephone interviews, physical examination, skin-prick tests, specific serum IgE and standardized, controlled and blinded oral food challenges. RESULTS: Two thousand three hundred and fifty-four individuals were contacted by mailed questionnaire, 739 (31.4%) responses could be fully evaluated. Four hundred and fifty-five (61.5%) participants reported symptoms related to food ingestion, 284 (38.4%) affirmed reproducible symptoms in the standardized telephone interview. One hundred and eighty-four (24.8%) individuals were fully examined. Reproducible symptoms to food were found in 31 (4.2%) children and adolescents: 26 (3.5%) showed symptoms of FA and five (0.7%) of NAFH. The oral allergy syndrome was most often observed. Foods most commonly identified by oral challenges were apple, hazelnut, soy, kiwi, carrot and wheat. CONCLUSION: The perception of food-related symptoms is common among children and adolescents from the general population. Self-reports could be confirmed in around one out of 10 individuals, still resulting in 4.2% of proven clinical symptoms. However, most reactions were mild and mainly because of pollen-associated FA, while NAFH reactions were less common. Severe IgE-mediated FA was observed in individuals with pre-existing atopic disease, who should be fully investigated for clinically relevant FA.     

Evaluation of allergenicity of genetically modified soybean protein extract in a murine model of oral allergen-specific sensitization

Background With the development of genetically modified crop plants there has been a growing interest in the approaches available to assess the potential allergenicity of novel gene products. For additional assessment of the potential allergenicity of expressed proteins, informative data can be generated using animal models. Soybean is one of the major source of protein in human and animal nutrition, and has also been well characterized as a major allergenic source. Advances in biotechnology have resulted in an increasing number of genetically engineered foods, and among these soybean is one of the most widespread. Objective To develop and characterize a murine model of IgE‐mediated soybean sensitization induced by intragastric immunization, in the presence of Cholera Toxin, with wild‐type soybean extract (wt‐SE) or with genetically modified soybean extract (gm‐SE). Methods Balb/c mice born in our animal facilities, from females fed on soy‐free food, were fed with the same soy‐free food and used in all the experiments. Mice were sensitized by gavages with soybean extracts, and allergen‐specific IgE and IgG responses were studied by direct ELISA and ELISA inhibition. Antigen‐specific cell proliferation and cytokine production were evaluated in spleen cell cultures. Results Sensitization with both soybean extracts induced high levels of antigen‐specific IgE and IgG1 and low levels of specific IgG2a. Both wt‐SE and gm‐SE were able to inhibit the binding of specific IgE from mice immunized with gm‐SE to the same antigen used for the ELISA coating. A comparable proliferative response was obtained with the homologous as well as with the heterologous extracts. Conclusion In sensitized mice, we observed a predominantly T‐helper type 2 (Th2)‐type immune response, with increased soybean‐specific IgE and IgG1 antibodies and a concomitant increase of IL‐4 and IL‐5 production. Results obtained by specific IgE ELISA inhibition and by antigen‐specific T cell proliferation demonstrated that wt‐SE and gm‐SE shared B and T epitopes. The present murine model of soybean sensitization established by the oral route should provide valuable information about risk assessment for food allergy from new proteins of genetically modified foods.     

Do shrimp‐allergic individuals tolerate shrimp‐derived glucosamine?

BACKGROUND: There is concern that shrimp-allergic individuals may react to glucosamine-containing products as shrimp shells are a major source of glucosamine used for human consumption. OBJECTIVE: The purpose of this study was to determine whether shrimp-allergic individuals can tolerate therapeutic doses of glucosamine. METHODS: Subjects with a history of shrimp allergy were recruited and tested for both shrimp reactivity via a prick skin test and shrimp-specific IgE by an ImmunoCAP assay. Fifteen subjects with positive skin tests to shrimp and an ImmunoCAP class level of two or greater were selected for a double-blind placebo-controlled food challenge (DBPCFC) using glucosamine-chondroitin tablets containing 1,500 mg of synthetically produced (control) or shrimp-derived glucosamine. Immediate reactions, including changes in peak flow and blood pressure, and delayed reactions (up to 24 h post-challenge) via questionnaire were noted and assessed. RESULTS: All subjects tolerated 1,500 mg of both shrimp-derived or synthetic glucosamine without incident of an immediate hypersensitivity response. Peak flows and blood pressures remained constant, and no subject had symptoms of a delayed reaction 24 h later. CONCLUSION: This study demonstrates that glucosamine supplements from specific manufacturers do not contain clinically relevant levels of shrimp allergen and therefore appear to pose no threat to shrimp-allergic individuals.     

Occupational allergic contact dermatitis and composition of acrylates in dentin bonding systems

Background Dentin-bonding systems contain sensitizing acrylates. They are increasingly used in dentistry, but only few cases of allergy have been encountered. Objective This study reports observations on eleven patients sensitized by acrylates in dentin-bonding compounds. Furthermore, the composition of dentin-bonding products was analysed and compared with the information given in the material safety data sheets. Methods Patch testing was performed to reveal allergic contact dermatitis, and chamber provocation tests to reveal possible respiratory sensitivity. Gas chromatography/mass spectrometry was used to analyse the chemical composition of the bonding products. Results The most common sensitizer in our material of eleven patients was 2-hydroxyethyl methacrylate (2-HEMA). Another putative sensitizer, BIS-GMA, used in dentin adhesives, did not cause sensitization. The typical allergic dermatitis localized to the fingertips (pulpitis). Seven of the eleven patients also developed paresthesia of the fingertips. One patient with positive patch test reactions to (meth)acrylates had pharyngitis hut no skin symptoms. One patient was sensitized because she had been patch tested with too high a concentration (undiluted) of dentin-bonding components. Material safety sheets gave inaccurate or wrong information about the contents. Conclusion Dentin-bonding acrylates are strong sensitizers, and even a single exposure may sensitize.     

Intake of unsaturated fatty acids and HDL cholesterol levels are associated with manifestations of atopy in adults

BACKGROUND: The increase in allergic diseases is still unexplained. It was hypothesized that the intake of unsaturated fatty acids is a contributing cause of this development. We investigated the relationship between serum cholesterol levels, intake of polyunsaturated fatty acids (PUFA) and manifestations of atopy in a population-based setting. METHODS: A nested case-control study was performed within the population of the 3rd MONICA survey in Augsburg (Germany). The serum levels of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol of 1537 adults (aged 28-78 years, response 61.4%) and the estimated intake of PUFA in a subset of 139 men were compared with the frequency of a doctor's diagnosis of asthma, allergic rhinoconjunctivitis (AR), atopic eczema (AE) and allergic sensitization as measured by skin prick and Radio Allergo Sorbent Test. FINDINGS: In bivariate analyses, we obtained a negative linear association between total and LDL cholesterol levels and the frequency of AR and sensitization, which was no longer significant after adjustment for important confounders. In contrast, positive linear associations were found between HDL cholesterol levels and AR and AE and, furthermore, between the intake of PUFA and allergic sensitization in men (P<0.01). After adjustment, an increasing risk for atopic diseases with increasing levels of HDL cholesterol and an increasing risk for allergic sensitization with increasing intakes of PUFA remained statistically significant. INTERPRETATION: There is indication that HDL cholesterol also plays a role in the complex interaction of fat intake, metabolism and the manifestation of atopy in adults. These findings may contribute to the understanding of time trends and regional differences of allergies.     

Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine

Recent evidence suggests that the putative dopamine (DA) autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232, share some neurochemical and behavioral effects with both psychostimulants and neuroleptics. The ability of (+)-AJ 76 and (+)-UH 232 to mimic or antagonize the stimulus effects of cocaine was investigated in rats trained to discriminate 5 mg/kg (N=8) or 10 mg/kg (N=8) of cocaine from saline in a two-lever, water-reinforced, drug discrimination task. In the cocaine (10 mg/kg) group, administration of (+)-AJ 76 (2.5–20 mg/kg) engendered only a partial substitution for cocaine (maximum 60% cocaine-lever responses). Given in combination with cocaine (10 mg/kg), (+)-AJ 76 (2.5–40 mg/kg) did not significantly attenuate the cocaine cue. A fixed dose of (+)-AJ 76 (2.5 or 10 mg/kg) plus various doses of cocaine (1.25–5 mg/kg) did not alter the cocaine dose-response curve. (+)-UH 232 (2–16 mg/kg) produced primarily saline-appropriate responding in rats trained to discriminate 5 mg/kg of cocaine and was unable to block the interoceptive cocaine state when given in combination with cocaine (5 mg/kg). (+)-UH 232 (2 or 8 mg/kg) also did not alter the cocaine dose-response curve. These results suggest that (+)-AJ 76 and (+)-UH 232 elicit only weak or no cocaine-like stimulus effects and, unlike neuroleptics, do not attenuate the cocaine cue.     

Patch testing with a mixture of 2 phenol-formaldehyde resins

1310 patients were routinely patch tested with a paratertiary-butylphenol-formaldehyde resin (PTBP-F-R), a resol resin based on phenol and formaldehyde (P-F-R-2), and a mixture of these 2 resins. Approximately 2.5 times more patients with contact allergy to phenol-formaldehyde resins were diagnosed when routinely patch tested with P-F-R-2 in addition to PTBP-F-R. Although patch testing with a mixture of both resins was not as good as patch testing with the 2 resins separately, it was better than testing only with PTBP-F-R, since 1.6 times more patients with contact allergy to phenol-formaldehyde resins were still diagnosed. P-F-R-2 is therefore recommended for routine patch testing, preferably as a separate patch test but otherwise as a mixture with PTBP-F-R.     

Contact dermatitis in patients with leg ulcers

100 patients with leg ulcers were patch tested against a standard battery of allergens. The readings were carried out daily from the 2nd to the 7th days. 55 patients showed positive reactions to one or more allergens. 32% of positive reactions developed for the first time after 48 h and 11% after 72 h. No single day or combination of two days gave 100% positive results. A single reading on the 4th day gave the highest number of positive reactions at 92%. The prevalence of positive patch tests was significantly higher in patients with surrounding eczema, and in patients with positive patch tests the ulcer duration was significantly longer than in those with negative patch tests. The total number of positive results in individuals increased linearly with the duration of the ulcer. Of allergens to which the ulcer was exposed, the occurrence of multiple sensitivity was significantly greater than predicted from the prevalence of individual sensitivities. However, there was no association between medicaments and metal sensitivity. This, together with the absence of an exponential rise in the number of allergens with the duration of ulcer, does not support the theory of systemic ampliative allergy.     

Latex allergy in infants younger than 1 year

BACKGROUND: The prevalence of latex allergy in children is increasing worldwide. Previous multiple operations or atopic predisposition are known risk factors. In contrast, only sporadic cases of latex allergy have been reported in infants younger than 1 year, and the causative latex-containing products or symptoms in young infants have not been studied in detail. OBJECTIVE: The purpose of this study is to analyse the symptoms and risk factors of latex allergy in young infants. METHODS: Cases of latex allergy in infants younger than 1 year were studied in detail. Clinical course, causative latex-containing products were spotted and detailed analysis for latex allergy in patients and patients' parents was performed. CONCLUSION: We report nine cases of latex allergy in infants younger than 1 year. None of them have any abnormality or previous operations. Six patients had atopic eczema/dermatitis syndrome, one patient had bronchial asthma, whereas two patients had no overt allergic diseases. Symptoms of latex allergy were wheezing, swelling of face or lips, facial rash, or anaphylaxis, and causative latex-containing products were teat, pacifier, nose cleaner, teether, balloon, or enema tube. All of the nine patients had positive skin prick test to latex and extract from causative latex-containing products, whereas eight patients had positive serum latex-specific IgE. Study for family history revealed that latex allergy was noted in either father or mother in six patients, in both father and mother in one patient, whereas no latex allergy was noted in parents in two patients. It should be noted that all of these patients had latex-induced symptoms at home. Latex allergy in young infants may not be unusual. Physicians should be aware of latex allergy, and care should be taken to avoid contact with latex in young infants, especially when there is family history for latex allergy.