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Biomedical subjects

Ronald van Ree

Publications and source records attributed to Ronald van Ree.

At least 19 recordsLinked to original sources
PubMed2007

Severe immediate allergic reactions to grapes: part of a lipid transfer protein-associated clinical syndrome.

BACKGROUND: Grape allergy is considered rare; grape lipid transfer protein (LTP; Vit v 1), an endochitinase and a thaumatin-like protein (TLP) have been reported as grape allergens. A considerable number of patients have referred to our department for severe reactions to grapes, and several IgE binding proteins were detected. OBJECTIVES: The aim of this study was to identify and characterise the allergens involved in severe allergic reactions to grapes and describe the population in which they occur. METHODS: Patients with reported severe allergic reactions to grapes (n = 37) are described. Grape allergens were purified/fractionated by a combination of chromatographic techniques, identified by proteomic analysis and biochemically characterised. Immunoreactivity was assessed by blot (inhibitions) and RAST (inhibitions), and skin prick tests were performed with the isolated allergens. RESULTS: All subjects were polyallergic, sensitised and reactive to several additional foods and pollen. All patients were sensitised to grape LTP. A 28-kDa expansin, a 37.5-kDa polygalacturonase-inhibiting protein, a 39-kDa beta-1,3-glucanase and a 60-kDa protein were identified as minor grape allergens. Endochitinase and TLP did not play a role. Inhibition experiments revealed the possible cross-reactive role of LTP for clinical sensitivities to other LTP-containing plant foods, but also the involvement of cross-reactive carbohydrate determinants of minor allergens in IgE cross-reactivity. CONCLUSIONS: LTP is the major grape allergen, while additional minor allergens may contribute to clinical reactivity. Severe grape allergy presents in atopic patients who frequently react to other LTP-containing, plant-derived foods. The 'LTP syndrome' is the appropriate term to describe this condition.

Adolescent↗
PubMed2007

IgE-mediated food allergy diagnosis: Current status and new perspectives.

In June 2005, the work of the EU Integrated Project EuroPrevall was started. EuroPrevall is the largest research project on food allergy ever performed in Europe. Major aims of the project are to generate for the first time reliable data on the prevalence of food allergies across Europe and on the natural course of food allergy development in infants. Improvement of in vitro diagnosis of food allergies is another important aim of the project. The present review summarizes current knowledge about the clinical presentation of food allergy and critically reviews available diagnostic tools at the beginning of the project period. A major problem in diagnosis is a relatively poor 'clinical specificity', i. e. both positive skin tests and in vitro tests for specific IgE are frequent in sensitized subjects without food allergy symptoms. So far, no in vitro test reliably predicts clinical food allergy. EuroPrevall aims at improving the predictive value of such tests by proceeding from diagnosis based on allergen extracts to purified allergen molecules, taking into account the affinity of the IgE-allergen interaction, and evaluating the potential of biological in vitro tests such as histamine release tests or basophil activation tests including assays performed with permanently growing cell lines.

Allergens↗
PubMed2007

Suspension-cultured BY-2 tobacco cells produce and mature immunologically active house dust mite allergens.

The replacement of crude allergen extracts by selected allergens currently represents a major goal for the improvement of allergy diagnosis and immunotherapy. Indeed, the development of molecularly defined vaccines would facilitate both standardization and enhance batch-to-batch reproducibility as well as treatment specificity. In this study, we have investigated the potential of tobacco plant cells to produce biologically active forms of the two major allergens from the house dust mite. A detailed characterization of these plant-made allergens has shown similar proteolytic maturation and folding as well as comparable immunoreactivity to their natural counterparts. Altogether, our results exemplify that suspension-cultured BY-2 tobacco cells represent a low cost and environmentally safe expression system suitable to produce recombinant allergens from Dermatophagoides pteronyssinus under a form appropriate for diagnostic and therapeutic purposes.

Allergens↗
PubMed2007

Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth Cohort Study.

OBJECTIVES: Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in infancy. METHODS: Information on antibiotic use in the first 6 months and eczema and wheeze until age 2 was collected by repeated questionnaires in 2764 families participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) Birth Cohort Study in The Netherlands. Antibiotic intake was evaluated both as maternal antibiotic use during breastfeeding and infant oral medication. Venous blood samples taken from 815 infants at 2 years of age were analyzed for total and specific immunoglobulin E against common food and inhalant allergens using a radioallergosorbent test. Multivariate logistic regression analysis was used to adjust for confounding factors. RESULTS: During the first 2 years, eczema was present in 32% of all infants, recurrent wheeze in 11%, and prolonged wheezing in 5%. At 2 years old, 27% of children were sensitized against > or = 1 allergen. At 6 months old, 11% had been exposed to antibiotics through breast milk and 20% directly through medication. The risk for recurrent wheeze, and prolonged wheeze was higher in infants directly exposed to antibiotics through medication, also after excluding from the analyses children who wheezed in the same period as an antibiotic had been used (avoiding reverse causation). Antibiotic use through breastfeeding was associated with recurrent wheeze, but prolonged wheeze was not. Eczema and sensitization were not associated with antibiotic exposure. CONCLUSIONS: We demonstrated that early antibiotic use preceded the manifestation of wheeze but not eczema or allergic sensitization during the first 2 years of life. Different biological mechanisms may underlie the etiology of wheeze compared with eczema or sensitization. Antibiotic exposure through breastfeeding enhanced the risk for recurrent wheeze, but this needs further confirmation.

Anti-Bacterial Agents↗
PubMed2006

Indoor allergens: relevance of major allergen measurements and standardization.

Major allergen measurements have relevance for the standardization of allergen extracts for immunotherapy and for epidemiologic studies into the cause of allergic diseases. Standardization is still centered around overall IgE-binding potencies (biological standardization). Major allergen levels show significant correlation with IgE-binding potencies, but ratios of the two can differ 5- to 10-fold between individual extracts. Major allergen quantities needed for effective and safe subcutaneous immunotherapy are proposed to be between 5 and 20 microg per maintenance shot. Although this figure is not really based on dose-finding studies, it has reached the status of a guiding principle. It is necessary to add major allergen measurements to standardization requirements to design adequate dosage schemes and elucidate the dose-response relation between major allergen dose and therapeutic effect. This will also help clarify to what extent sublingual immunotherapy requires higher doses of major allergen. Fine specificity of different assays toward isoforms and other variants of single allergens often results in diverging allergen measurements. Standardization should be based on certified major allergen references and accompanying assays that are cross-reactive enough to recognize all variants to facilitate comparability. This will also ensure that primary and secondary prevention strategies aiming at regulating allergen exposure will stay on solid ground.

Air Pollution, Indoor↗
PubMed2006

Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study.

BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.

Bacteria↗
PubMed2006

Effect of postharvest storage on the expression of the apple allergen Mal d 1.

Consumption of fresh apples can cause allergy in susceptible individuals. A competitive enzyme-linked immunosorbent assay (ELISA) has been developed to determine Mal d 1 levels in apple pulp using a monoclonal antibody (BIP-1). The ELISA was able to rank ten cultivars according to their Mal d 1 content (between 3.8 and 72.5 mug/g pulp). For the first time, it has been demonstrated that growing conditions and postharvest storage, using three different treatments over a 5 month period in 2 consecutive years, increase Mal d 1 expression at a translational and transcriptional level (3.5- and 8.5-fold under controlled atmosphere storage). Expression of three major Mal d 1 isoforms was observed by real-time polymerase chain reaction over the 5 month storage period, and Mal d 1.02 was the most highly expressed isoform. In conclusion, Mal d 1 gene expression was significantly increased during modified atmosphere storage. Individuals suffering from birch pollen-apple allergy syndrome might experience fewer problems consuming freshly picked apples.

Allergens↗
PubMed2006

Maturity and storage influence on the apple (Malus domestica) allergen Mal d 3, a nonspecific lipid transfer protein.

Consumption of apples can provoke severe allergic reactions, in susceptible individuals, due to the presence of the allergen Mal d 3, a nonspecific lipid transfer protein, found largely in the fruit skin. Levels of Mal d 3 were determined in peel as a function of apple cultivar, position of the fruit growing on the tree, apple maturity, and postharvest storage by ELISA. As the apples mature, Mal d 3 levels increased, although the rate was dependent on cultivar and tree position. During storage, levels of Mal d 3 decreased in all cultivars (cvs. Cox, Jonagored, and Gala), the rate of overall decrease being greatest under controlled atmosphere conditions. There was no correlation between Mal d 3 levels and total apple peel protein, indicating specific alterations in Mal d 3 expression. Thus pre- and postharvest treatments (i.e., storage) can modify the allergen load in apple peel, the highest levels being found in overly mature and freshly harvested fruits.

Allergens↗
PubMed2006

Effect of in vitro gastric and duodenal digestion on the allergenicity of grape lipid transfer protein.

BACKGROUND: Severe grape allergy has been linked to lipid transfer protein (LTP) sensitization. LTPs are known to be resistant to pepsin digestion, although the effect of gastroduodenal digestion on its allergenicity has not been reported. OBJECTIVE: We sought to investigate the effect of gastric and gastroduodenal digestion on the allergenic activity of grape LTP. METHODS: The proteolytic stability of grape LTP was investigated by using an in vitro model of gastrointestinal digestion. The allergenicity of LTP and its digesta was assessed in vitro by means of IgE immunoblotting, RASTs, and in vivo skin prick tests in the same patients with grape allergy. RESULTS: Grape LTP was resistant to gastric digestion, and yielded a 6000-d relative molecular mass C-terminally trimmed fragment after duodenal digestion. This fragment retained the in vitro IgE reactivity of the intact protein. Inclusion of phosphatidylcholine during gastric digestion protected the LTP to a limited extent against digestion. Digestion did not affect the in vivo (skin prick test) biologic activity of LTP. CONCLUSION: The allergenic activity of grape LTP was highly resistant to in vitro digestion. This property might facilitate sensitization through the gastrointestinal tract and might also potentiate the ability of LTPs to elicit severe allergic reactions in sensitized individuals. CLINICAL IMPLICATIONS: Purified natural allergens will facilitate the development of component-resolved diagnostic approaches, including allergen chips. This study contributes to our understanding of the role digestion plays in symptom elicitation in true food allergy.

Allergens↗
PubMed2006

Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods.

BACKGROUND: Allergy to a plant food can either result from direct sensitization to that food or from primary sensitization to pollen, latex, or another food. OBJECTIVE: We sought to investigate the primary sensitizers in apple allergy across Europe, the individual allergens involved, and whether these differences determine the clinical presentation. METHODS: Patients (n = 389) with positive case histories and skin prick test responses to fresh apple were selected in the Netherlands, Austria, Italy, and Spain. Skin prick tests and RASTs to a panel of pollens and plant foods were performed, as well as RASTs to Bet v 1 and the apple allergens Mal d 1, 2, 3, and 4. RESULTS: In the Netherlands, Austria, and Italy apple allergy is mild (>90% isolated oral symptoms) and related to birch pollinosis and sensitization to Bet v 1 and its apple homologue, Mal d 1, which has an odds ratio of local reactions of 2.85 (95% CI, 1.47-5.55). In Spain apple allergy is severe (>35% systemic reactions) and related to peach allergy and sensitization to Mal d 3 (nonspecific lipid transfer protein), which has an odds ratio of systemic reactions of 7.76 (95% CI, 3.87-15.56). CONCLUSION: The analysis of individual apple allergens in a clinical context has provided insight into the sensitization pathway and into the intrinsic risk an allergen bears to induce mild or severe food allergy. CLINICAL IMPLICATIONS: Information on the sensitization pathway is essential to develop preventive strategies in food allergy. The application of individual food allergens with a known intrinsic risk will improve the prognostic value of diagnostic tests.

Adult↗
PubMed2006

Cooking birch pollen-related food: divergent consequences for IgE- and T cell-mediated reactivity in vitro and in vivo.

BACKGROUND: The major birch pollen allergen Bet v 1 cross-reacts with homologous food allergens, resulting in IgE-mediated oral allergy syndromes (OASs). To avoid this food, allergy allergologists and guidebooks advise patients to consume birch pollen-related foods after heating. OBJECTIVE: We sought to evaluate whether cooked Bet v 1-related food allergens induce IgE- and T cell-mediated reactions in vitro and in vivo. METHODS: Recombinant Bet v 1, Mal d 1 (apple), Api g 1 (celery), and Dau c 1 (carrot) were incubated at increasing temperatures. Protein structures were determined by means of circular dichroism. Mediator release was tested in basophil activation assays. PBMCs and Bet v 1-specific T-cell lines with known epitope specificity were stimulated with native and cooked food allergens. Patients with birch pollen allergy who experienced OAS and the exacerbation of atopic dermatitis (AD) on ingestion of fresh apple, celery, or carrot were retested in double-blind, placebo-controlled food challenges with the respective foods in cooked form. RESULTS: In vitro, cooked food allergens lost the capacity to bind IgE and to induce mediator release but had the same potency to activate Bet v 1-specific T cells as native proteins. In vivo, ingestion of cooked birch pollen-related foods did not induce OAS but caused atopic eczema to worsen. CONCLUSION: T-cell cross-reactivity between Bet v 1 and related food allergens occurs independently of IgE cross-reactivity in vitro and in vivo. In patients with AD, the resulting immune reaction can even manifest as late eczematous skin reactions. Therefore the view that cooked pollen-related foods can be consumed without allergologic consequences should be reconsidered. CLINICAL IMPLICATIONS: Symptom-free consumed pollen-related food allergens might cause T cell-mediated late-phase skin reactions in patients with pollen allergy and AD.

Allergens↗
PubMed2006

An antibody produced in tobacco expressing a hybrid beta-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes.

N-glycosylation of a mAb may have a major impact on its therapeutic merits. Here, we demonstrate that expression of a hybrid enzyme (called xylGalT), consisting of the N-terminal domain of Arabidopsis thaliana xylosyltransferase and the catalytic domain of human beta-1,4-galactosyltransferase I (GalT), in tobacco causes a sharp reduction of N-glycans with potentially immunogenic core-bound xylose (Xyl) and fucose (Fuc) residues as shown by Western blot and MALDI-TOF MS analysis. A radioallergosorbent test inhibition assay with proteins purified from leaves of WT and these transgenic tobacco plants using sera from allergic patients suggests a significant reduction of potential immunogenicity of xylGalT proteins. A mAb purified from leaves of plants expressing xylGalT displayed an N-glycan profile that featured high levels of galactose, undetectable xylose, and a trace of fucose. Hence, a transgenic plant expressing the hybrid GalT might yield more effective and safer monoclonals for therapeutic purposes than WT plants and even transgenic plants expressing the unchanged GalT.

Antibodies↗
PubMed2006

Cloning of oleosin, a putative new hazelnut allergen, using a hazelnut cDNA library.

The clinical presentation of non-pollen related allergy to hazelnut can be severe and systemic. So far, only a limited number of non-pollen related hazelnut allergens have been identified and characterized. The aim of this study was to identify and clone new hazelnut allergens. A lambda ZAP cDNA library of hazelnut was constructed. The library was screened with serum of six hazelnut allergic patients displaying different IgE-binding patterns on hazelnut immunoblot. Rapid amplification of cDNA ends (RACE) protocols were applied to obtain full-length clones. Expression experiments were carried out in Eschericchia coli. Expression was monitored by SDS-PAGE, protein staining and immunoblotting. A hazelnut cDNA library was constructed. IgE screening resulted in the cloning of two isoforms of a novel putative hazelnut allergen. The clones were identified as oleosins, with theoretical molecular masses of 16.7 and 14.7 kDa and pI of 10.5 and 10.0, respectively. The isoforms demonstrated only 37% amino acid sequence identity but contained the typical hydrophobic stretch in the middle of the protein (53% identity) with the characteristic oleosin proline knot region (11/12 amino acids identical). Expression in E. coli of the longer isoform resulted in a clear band on SDS-PAGE. The expressed protein was recognized on an immunodot blot by IgE from serum that was used for screening the cDNA library. Hazelnut contains multiple isoforms of oleosin. IgE binding of a hazelnut-allergic patient to a recombinant version suggest that hazelnut oleosin is an allergen, as has been described for peanut and sesame.

Amino Acid Sequence↗
PubMed2006

Allergen-specific IgE testing in the diagnosis of food allergy and the event of a positive match in the bioinformatics search.

Current documents on risk assessment of genetically modified foods recommend including IgE-binding tests on sera from allergic patients. However, there is no generally accepted recommendation on technical aspects of the testing procedures or on the interpretation of the results, despite that fact that both false positive and false-negative results may be caused by variability of the test procedures. The present article discusses the state-of-the-art of serological test procedures for qualitative and quantitative determination of specific IgE and interpretation of test results. It is emphasized that the use of sera from clinically well-characterized subjects is of high importance. In the case of a positive test result, the biological activity of the detected IgE antibodies, i. e., the potential to trigger mediator release from basophils or mast cells in an allergen-specific manner, should be taken into account. However, present data also indicate that validation of such mediator release tests is required, both in terms of experimental protocols and with respect to correlation of the test results with the clinical situation. Further studies are also required to prove the usefulness of targeted serum screening, i. e., the testing of gene products from organisms not known to be allergenic with sera from subjects allergic to related species.

Allergens↗
PubMed2005

IgE binding to pepsin-digested food extracts.

BACKGROUND: Pepsin resistance of allergens like lipid transfer protein and 2S albumin has been suggested as explanation for the severity of symptoms often induced by these allergens. Component-resolved diagnosis with purified labile and stable allergens has therefore been proposed to better characterize the risk involved in a positive in vitro IgE test. However, for many foods, purified allergens are not (yet) available. OBJECTIVE: It was the aim of this study to evaluate the potential of pepsin-digested whole-food extracts to distinguish between IgE responses to stable (potentially severe) and labile (mild) allergens. METHODS: Sera (n = 143) from Italian, Spanish and Dutch patients with hazelnut and/or apple ingestion-related symptoms were analyzed for residual IgE binding to pepsin-resistant hazelnut and/or apple allergens. Control and pepsin-digested hazelnut and apple extracts were used for radioallergosorbent test analysis and immunoblot analysis. RESULTS: Pepsin digestion of food extracts, like from hazelnut and apple used for in vitro diagnostic tests, provides a way to distinguish sensitization to pepsin-resistant allergens from that to pepsin-susceptible allergens. In this selected group of patients, IgE reactivity to pepsin-digested extracts correlated with sensitization to the stable allergen lipid transfer protein. The analysis further revealed that the use of soluble pepsin can result in false-positive in vitro tests (2/143). CONCLUSION: Pepsin-digested food extracts are a convenient tool to identify patients with IgE antibodies against potentially dangerous stable allergens, in particular for those foods where the relevant stable allergens have not yet been identified. This can increase the clinical prognostic value of food allergy serology.

Allergens↗
PubMed2005

In vivo assessment with prick-to-prick testing and double-blind, placebo-controlled food challenge of allergenicity of apple cultivars.

BACKGROUND: Apple cultivars have been reported to differ in allergenicity on the basis of in vitro and skin prick tests with apple extracts. OBJECTIVES: We sought to evaluate the efficacy of the prick-to-prick method in assessing differences in allergenicity of apple cultivars and to confirm differences by means of double-blind, placebo-controlled food challenge (DBPCFC). METHODS: Intra-assay and intracultivar variation of prick-to-prick test results were determined in 6 Dutch and 8 Spanish patients with apple allergy by using 5 apples of the cultivars Golden Delicious, Fuji, and Ecolette in duplicate. In addition, 21 cultivars were screened for allergenicity in 15 Dutch patients with birch pollen and apple allergy. Two selected cultivars (Golden Delicious and Santana) were tested with DBPCFCs. The influence of storage conditions on allergenicity was assessed in 5 cultivars. RESULTS: Intra-assay variation of skin prick testing was 3.9%, and intracultivar variation was 4.1%. A ranking of 21 cultivars was made on the basis of prick-to-prick tests in 9 patients. Apple cultivars were classified as of low, intermediate, and high allergenicity, with a significant difference between low and high allergenicity (P < .001). A significant difference in allergenicity determined between Golden Delicious and Santana cultivars (P < .05) was confirmed by means of DBPCFC. With 5 cultivars, controlled atmosphere (2.5% oxygen/1% carbon dioxide) was shown to reduce allergenicity (P < .001) by 15% compared with storage at 2 degrees C. CONCLUSIONS: Prick-to-prick testing with fresh apples is a reproducible method of assessing allergenicity. Apples can be classified as of low or high allergenicity for the majority of patients. This was confirmed by using DBPCFCs. Selection of cultivars and control of storage conditions are both viable strategies for reduction of symptoms in patients with apple allergy.

Allergens↗
PubMed2005

Lipid transfer proteins from fruit: cloning, expression and quantification.

BACKGROUND: Lipid transfer proteins (LTP) are stable, potentially life-threatening allergens in fruits and many other vegetable foods. The aim of this study was to clone and express recombinant apple LTP (Mal d 3), as has previously been done for peach LTP (Pru p 3) and set up quantitative tests for measuring fruit LTPs. METHODS: cDNA for Mal d 3 and Pru p 3 was cloned, expressed in the yeast Pichia pastoris and the resulting proteins were purified via cation exchange chromatography. The immune reactivity of rMal d 3 was compared to nMal d 3 by RAST (inhibition), immunoblotting and basophil histamine release testing. To obtain monoclonal and monospecific polyclonal antibodies, mice and rabbits were immunized with purified nMal d 3. RESULTS: The deduced amino acid sequence of Mal d 3 was identical to the published sequence, Pru p 3 differed at two positions (S9A and S76H). The rMal d 3 had an IgE-binding potency and biological activity close to its natural counterpart. One sandwich ELISA selectively detecting apple LTP and another cross-reactive with cherry, nectarine and hazelnut LTP were developed. In addition, a competitive RIA was developed with polyclonal rabbit antiserum and labeled nMal d 3. CONCLUSION: rMal d 3 (as shown before for rPru p 3) may be a useful tool for application in component-resolved diagnosis of food allergy. Assays for the measurement of LTP will increase the traceability of this potentially dangerous allergen.

Allergens↗