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Notes: The effect of the systemic administration of a novel, orally active, catechol-O-methyltransferase (COMT) inhibitor, Ro 40–7592, on the in vivo extracellular concentrations of dopamine (DA) and its metabolites, dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA), was studied by transcerebral microdialysis in the dorsal caudate of freely moving rats. Ro 40–7592 (at doses of 3.0, 7.5, and 30 mg/kg p.o.) elicited a marked and long-lasting reduction of HVA, and at doses of 7.5 and 30 mg/kg, an increase of DOPAC output, but it failed to increase DA output. The administration of L-β-3,4-dihydroxyphenylalanine (L-DOPA, 20 and 50 mg/kg p.o.) with a DOPA decarboxylase inhibitor (benserazide) increased both HVA and DOPAC output, but failed to modify significantly extracellular DA concentrations in dialysates; in contrast, combined administration of L-DOPA + benserazide with Ro 40–7592 (30 mg/ kg p.o.) resulted in a significant increase in DA output. Ro 40–7592 prevented the L-DOPA-induced increase in HVA output and markedly potentiated the increase in DOPAC output. To investigate to what extent the increase in extra cellular DA concentrations was related to an exocitotic release, tetrodotoxin (TTX) sensitivity was tested. Addition of TTX to Ringer, although abolishing DA output in the absence of L-DOPA, partially reduced it in the presence of L-DOPA + Ro 40–7592 and even more so after L-DOPA without the COMT inhibitor. The results of the present study suggest that metabolism through COMT regulates extracellular concentrations of DA formed from exogenously administered L-DOPA but not of endogenous DA. Therefore, inhibition of COMT results in a potentiation of L-DOPA effects not only by inhibition of its peripheral metabolism (conversion to 3-methoxy-DOPA), but also by inhibition of the metabolism of its active metabolite, DA, in the brain.

Notes: A female patient experienced a severe allergic reaction after consumption of vineyard snails. The patient proved to be sensitized to house-dust mite (HDM) and demonstrated a positive skin test and specific IgE to snail (Eobania vermiculata, Lofarma). The snail RAST was 〉 80% inhibited by HDM, whereas the mite RAST was 〈 10% inhibited by snail extract. This is possibly another example of food allergy related to primary sensitization by an aeroallergen.

Notes: Background:  Non-specific lipid transfer proteins (LTPs) are involved in allergy to fresh and processed fruits. We have investigated the effect of thermal treatment and glycation on the physico-chemical and IgE-binding properties of the LTP from apple (Mal d 3).Methods:  Mal d 3 was purified from apple peel and the effect of heating in the absence and presence of glucose investigated by CD spectroscopy, electrospray and MALDI-TOF mass spectrometry. IgE reactivity was determined by RAST and immunoblot inhibition, SPT and basophil histamine release test.Results:  The identity and IgE reactivity of purified Mal d 3 was confirmed. Mild heat treatment (90°C, 20 min) in the absence or presence of glucose did not alter its IgE reactivity. More severe heat treatment (100°C, 2 h) induced minor changes in protein structure, but a significant decrease in IgE-binding (30-fold) and biological activity (100- to 1000-fold). Addition of glucose resulted in up to four glucose residues attached to Mal d 3 and only a 2- and 10-fold decrease of IgE-binding and biological activity, respectively.Conclusions:  Only severe heat treatment caused a significant decrease in the allergenicity of Mal d 3 but glycation had a protective effect. The presence of sugars in fruits may contribute to the thermostability of the allergenic activity of LTP in heat-processed foods.

Notes: Background:  Jackfruit allergy has been reported just once. It is unknown whether this food allergy is caused by direct sensitization or cross-sensitization to pollen allergens.Objective:  Establish whether jackfruit allergy is linked to birchpollen allergy.Methods:  Two jackfruit allergic patients and five patients with birchpollen-related apple allergy were recruited. Sensitization to pollen and plant foods was assessed by skin prick test (SPT), radio-allergosorbent test (RAST) and immunoblot. RAST analysis was performed for Bet v 1 and Mal d 1. Cross-reactivity was evaluated by RAST and immunoblot-inhibition. Biological activity of immunoglobulin E (IgE) was measured by basophil histamine release. Allergy to jackfruit was evaluated by double-blind placebo-controlled food challenge (DBPCFC) or open challenge (OC).Results:  In both patients DBPCFC confirmed the reported jackfruit allergy. SPT was 41 and 27 mm2 and specific IgE to jackfruit was 5.9 and 0.8 IU/ml, respectively. Immunoblot analysis revealed IgE reactivity at Mr of approximately 17 kDa. The Bet v 1-related nature of this allergen in jackfruit was demonstrated by RAST and immunoblot inhibition. To assess whether jackfruit allergy might be common in patients with combined birchpollen-fruit allergy, five such patients underwent an OC with jackfruit. All five had OA-like symptoms.Conclusions:  Jackfruit allergy can be added to the list of birchpollen-related food allergies. Increased consumption of this fruit will result in a rise in allergic reactions.

Notes: The cross-reactivity of IgE antibodies is of interest for various reasons, three of which are discussed. Firstly, from the clinical view, it is important to know the patterns of cross-reactivity, because they often (but not always) reflect the pattern of clinical sensitivities. We discuss the cross-reactivities associated with sensitization to pollen and vegetable foods: PR-10 (Bet v 1-related), profilin, the cross-reactive carbohydrate determinant (CCD), the recently described isoflavone reductase, and the (still elusive) mugwort allergen that is associated with celery anaphylaxis; cross-reactivities between allergens from invertebrates, particularly tropomyosin, paramyosin, and glutathione S-transferase (GST); and latex-associated cross-reactivities. Clustering cross-reactive allergens may simplify diagnostic procedures and therapeutic regimens. Secondly, IgE cross-reactivity is of interest for its immunologic basis, particularly in relation to the regulation of allergic sensitization: are IgE antibodies to allergens more often cross-reactive than IgG antibodies to “normal” antigens? If so, why? For this discussion, it is relevant to compare not only the structural relation between the two allergens in question, but also the relatedness to the human equivalent (if any) and how the latter influences the immune repertoire. Thirdly, prediction of IgE cross-reactivity is of interest in relation to allergic reactivity to novel foods. Cross-reactivity is a property defined by individual antibodies to individual allergens. Quantitative information (including relative affinity) is required on cross-reactivity in the allergic population and with specific allergens (rather than with whole extracts). Such information is still scarce, but with the increasing availability of purified (usually recombinant) allergens, such quantitative information will soon start to accumulate. It is expected that similarity in short stretches of the linear amino-acid sequence is unlikely to result in relevant cross-reactivity between two proteins unless there is similarity in the protein fold.

Notes: For most foods, true standardization is not yet feasible because there is insufficient information on the relative importance of individual allergens and their variants. Standardization without sufficient information may easily be counterproductive because improvements are less likely to be implemented. In the analysis of natural test material, the following principles apply:〈list xml:id="l1" style="custom"〉1) RAST inhibition is usually inferior to other means of allergen quantitation.2) Immunoblot is inefficient for some “important” allergens and over-efficient for some “unimportant” allergens and may therefore be deceptive.3) Single-component assays are the only satisfactory way to describe complex mixtures.Improving the actual food-testing procedure is important, but will not alone result in a reliable diagnostic procedure. Tests for measuring “effect modifiers” will have to be developed in order to predict in vivo reactions to foods.

Notes: A group of 28 patients from Italy was studied who had asthma after consumption of snail. All patients also had asthma and/or rhinitis caused by house-dust mite. RAST analyses confirmed the combined sensitization to snail and mite. In a few sera, IgE antibodies reactive with other foods of invertebrate origin (mussel and shrimp) were detected. RAST inhibition showed that most IgE antibodies against snail were cross-reactive with house-dust mite. In contrast, the mite RAST was not significantly inhibited by snail. This indicates that house-dust mite was the sensitizing agent. Immunoblot analyses revealed multiple bands in snail extract recognized by IgE. In contrast to what has been described for cross-reactivity between shrimp and mite, tropomyosin played only a minor role as a cross-reactive allergen in these patients. The observations in this study indicate that snail consumption can cause severe asthmatic symptoms in house-dust-mite-allergic patients. It might, therefore, be advisable to screen mite-allergic asthma patients for allergy to snail and other invertebrate animal foods.

Notes: Background: Lipid transfer proteins (LTP) are highly conserved and widely distributed throughout the plant kingdom. Recent studies demonstrated immunological cross-reactivity between LTP from many botanically unrelated fruits and vegetables and concluded that LTP are pan-allergens. This study aimed to evaluate the clinical relevance of such cross-reactivity in a group of subjects monosensitized to LTP.Methods: Twenty LTP-hypersensitive patients were selected from a population of about 600 subjects with history of Rosaceae allergy by means of: 1) negative skin prick test (SPT) with a commercial birch pollen extract; 2) positive SPT with a commercial plum extract, rich in LTP but virtually lacking both Bet v 1-like proteins and profilin; 3) in-vitro IgE reactivity to the 9–10 kDa fraction of peach peel or immunoblot with peach peel showing a single band at 10 kDa; and 4) total inhibition of reactivity to whole peach extract (containing Bet v 1-related allergen, profilin, and LTP) by purified peach LTP on enzyme-linked immunoassay (ELISA). Allergy to foods other than Rosaceae was ascertained by careful interview and analysis of medical recordings. SPT with a large series of plant-derived foods were carried out as well. The cross reactivity between LTPs from botanically unrelated plant-derived foods was assessed by ELISA inhibition tests using walnut and peanut extracts as substrate, and peach LTP as inhibitor.Results: All patients reported allergic reactions after the ingestion of at least one from a large number of vegetable foods other than Rosaceae, and in several cases clinical reactions were very severe (anaphylaxis, asthma, urticaria/angioedema). Nuts and peanuts were the most frequently reported causes of allergic reactions (80% and 40% of patients, respectively). All patients showed positive SPT to several non-Rosaceae food extracts. SPT with nuts, peanut, legumes, celery, rice, and corn were positive in the majority of patients. In ELISA inhibition studies, absorption of sera with peach LTP caused complete inhibition of IgE reactivity to walnut and peanut in all cases.Conclusion: LTP is a clinically relevant pan-allergen. Most Rosaceae-allergic, LTP-hypersensitive patients experience adverse reactions after ingestion of botanically unrelated plant-derived foods as well. In view of the high prevalence and severity of the allergic reactions induced, hazelnut, walnut, and peanut should be regarded as potentially hazardous for these patients.