Biomedical subjects

André H Penninks

Publications and source records attributed to André H Penninks.

8 recordsLinked to original sources

PubMed2007

The importance of dietary control in the development of a peanut allergy model in Brown Norway rats.

This report describes the further development of a peanut allergy model in Brown Norway (BN) rats and in particular the importance of allergen-free breeding of the laboratory animals for the allergen to be used. For this purpose BN rats were bred for 3 generations on soy- and peanut-free feed since it is known that the legumes peanut and soy are cross-reactive. In addition, the effect of cholera toxin (CT), an oral adjuvant often used to increase the sensitivity of food allergy models, was investigated in the BN rat model. BN rats that were bred on both soy- and peanut-free feed could be sensitized orally to peanut (all exposed rats developed peanut-specific IgE, IgG2a and IgG1) and the adjuvant CT could only enhance this sensitization to a limited extent. We also found different protein recognition patterns against purified peanut allergens (Ara h1, Ara h2 and Ara h3) between intraperitoneally (i.p.) and orally sensitized BN rats. Orally sensitized rats recognized all tested allergens whereas i.p. sensitized rats only recognized Ara h1 and Ara h2. Our conclusion is that a model for food allergy should preferably be (A) oral and (B) if possible without the use of adjuvantia. Our model in BN rats unites these preferred characteristics. In addition, we show the importance of dietary control when conducting oral sensitization studies. Special attention must be paid to unscheduled dietary pre-exposure of the animals to the protein under investigation to obtain optimal oral sensitization.

Adjuvants, Immunologic↗

PubMed2005

Recent advances using rodent models for predicting human allergenicity.

The potential allergenicity of newly introduced proteins in genetically engineered foods has become an important safety evaluation issue. However, to evaluate the potential allergenicity and the potency of new proteins in our food, there are still no widely accepted and reliable test systems. The best-known allergy assessment proposal for foods derived from genetically engineered plants was the careful stepwise process presented in the so-called ILSI/IFBC decision tree. A revision of this decision tree strategy was proposed by a FAO/WHO expert consultation. As prediction of the sensitizing potential of the novel introduced protein based on animal testing was considered to be very important, animal models were introduced as one of the new test items, despite the fact that non of the currently studied models has been widely accepted and validated yet. In this paper, recent results are summarized of promising models developed in rat and mouse.

Administration, Oral↗

PubMed2005

Reversible denaturation of Brazil nut 2S albumin (Ber e1) and implication of structural destabilization on digestion by pepsin.

The high resistance of Brazil nut 2S albumin, previously identified as an allergen, against proteolysis by pepsin was examined in this work. Although the denaturation temperature of this protein exceeds the 110 degrees C at neutral pH, at low pH a fully reversible thermal denaturation was observed at approximately 82 degrees C. The poor digestibility of the protein by pepsin illustrates the tight globular packing. Chemical processing (i.e., subsequent reduction and alkylation of the protein) was used to destabilize the globular fold. Far-UV circular dichroism and infrared spectroscopy showed that the reduced and alkylated form had lost its beta-structures, whereas the alpha-helix content was conserved. The free energy of stabilization of the globular fold of the processed protein as assessed by a guanidine titration study was only 30-40% of that of the native form. Size exclusion chromatography indicated that the heavy chain lost its globular character once separated from the native 2S albumin. The consequences of these changes in structural stability for degradation by pepsin were analyzed using gel electrophoresis and mass spectrometry. Whereas native 2S albumin was digested slowly in 1 h, the reduced and alkylated protein was digested completely within 30 s. These results are discussed in view of the potential allergenicity of Brazil nut 2S albumin.

2S Albumins, Plant↗

PubMed2004

Food allergy: what do we learn from animal models?

PURPOSE OF REVIEW: This review summarizes selected articles on animal models of food allergy published in 2003. The research areas that are covered include mechanistic studies, the search for new therapies, as well as screening models for hazard identification of potential allergens. RECENT FINDINGS: Novel treatment options of both prevention and therapeutic strategies have been reported with promising results. The induction of de-sensitization to food proteins was achieved by exposure to a mixture of recombinant food allergens and T helper 1 (Th1)-skewing bacterial components. Furthermore, research in animal models has provided new insights into the role of protein structure, digestion, and gut permeability in sensitization and tolerance induction to food proteins. The Th2 hypothesis of food allergy was tested in mouse strains, linking genetic susceptibility to sensitization with differential Th1-Th2 responses. In this context, the role of the liver in development of food antigen-specific Th2 cells, and the importance of costimulatory molecules in Th2 skewing were demonstrated. Finally, rodent models to predict potential allergenicity of novel foods have been further developed using different routes of sensitization. SUMMARY: Currently, several animal models of food allergy are used, including mouse, rat, swine, and dog. Continuing research in these models may elucidate the immunological mechanisms that underlie the sensitization and challenge phase of food allergy and may result in improved therapeutic options. Furthermore, the development of animal models to predict relative allergenicity of novel foods remains an important topic.

Animals↗

PubMed2003

How accurate and safe is the diagnosis of hazelnut allergy by means of commercial skin prick test reagents?

BACKGROUND: Allergy to tree nuts, like hazelnuts, ranks among the most frequently observed food allergies. These allergies can start at early childhood and are, in contrast to other food allergies, not always outgrown by the patient. Tree nut allergy is frequently associated with severe reactions. Diagnosis partially relies on in vivo testing by means of a skin prick test (SPT) using commercially available SPT reagents. METHODS: Protein and allergen composition of nine commercial SPT solutions was evaluated using standard protein detection methods and specific immunoassays for measurement of five individual allergens. Diagnostic performance was assessed by SPT in 30 hazelnut-allergic subjects, of which 15 were provocation proven. RESULTS: Protein concentrations ranged from 0.2-14 mg/ml. SDS-PAGE/silver staining revealed clear differences in protein composition. The major allergen Cor a 1 was present in all extracts but concentrations differed up to a factor 50. An allergen associated with severe symptoms, Cor a 8 (lipid transfer protein), was not detected on immunoblot in three products, and concentrations varied by more than a factor 100 as was shown by RAST inhibition. Similar observations were made for profilin, thaumatin-like protein and a not fully characterized 38-kD allergen. Ratios of individual allergens were variable among the nine extracts. SPT showed significant difference, and 6/30 patients displayed false-negative results using 3/9 products. CONCLUSION: Variability in the composition of products for the diagnosis of hazelnut allergy is extreme. Sometimes, allergens implicated in severe anaphylaxis are not detected by immunoblotting. These shortcomings in standardisation and quality control can potentially cause a false-negative diagnosis in subjects at risk of severe reactions to hazelnuts.

Adolescent↗

PubMed2003

Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.

The need for widely accepted and validated animal models to test the potential allergenicity and potency of novel (biotechnology-derived) proteins has become an important issue for their safety evaluation. In this article, we summarize the results of the development of an oral sensitization protocol for food proteins in the rat. Young Brown Norway rats were exposed to either various purified allergenic proteins (e.g., ovalbumin, partly purified), a whole food (cow's milk), or total protein extracts (hen's egg white, peanut) by daily gavage dosing during 42 days without the use of an adjuvant. The results showed that Brown Norway rats can be sensitized orally to the various allergenic food proteins tested, resulting in antigen-specific immunoglobulin (Ig) G and IgE responses, without the use of adjuvants. Animals orally exposed to cow's milk or total protein extracts of egg white also developed specific IgE and IgG antibodies that recognized the same proteins compared with antibodies from patients allergic to egg white or cow's milk. We also studied local and systemic immune-mediated effects. In ovalbumin-sensitized rats, some clinical symptoms of food allergy were studied upon an oral challenge with ovalbumin. The results demonstrated that gut permeability was increased and that in some animals breathing frequency and systolic blood pressure were temporarily decreased. The results obtained show that the Brown Norway rat provides a suitable animal model for food allergy research and for the study of relative allergenicity of existing and novel food proteins.

Administration, Oral↗

PubMed2002

The distribution of individual threshold doses eliciting allergic reactions in a population with peanut allergy.

BACKGROUND: Hidden peanut in consumer products can endanger patients with peanut allergy. Individual threshold doses for eliciting allergic reactions need to be elucidated to assess the risks for development of allergic reactions after accidental ingestion of peanut in a population with peanut allergy. OBJECTIVE: We sought to determine the distribution of individual threshold doses in a population with peanut allergy and to correlate these thresholds to the severity of peanut-induced symptoms. METHODS: Twenty-six adult patients with a convincing history of peanut-related symptoms, a specific IgE level of 0.7 kU/L or greater, or a positive skin prick test response of 2+ or greater to peanut were included. These patients underwent double-blind, placebo-controlled food challenges with increasing doses of peanut. A threshold dose could be established when objective or repetitive subjective reactions occurred after active doses. RESULTS: All patients had subjective oral symptoms (n = 26), prior subjective gastrointestinal symptoms (n = 14), or objective symptoms (n = 5). Reactions started within 30 minutes after ingestion of peanut, but in 2 patients additional symptoms were delayed by 1 to 2 hours. Threshold doses for allergic reactions ranged from a dose as low as 100 microg up to 1 g of peanut protein. Fifty percent of the study population (95% CI, 30%-70%) already had an allergic reaction after ingestion of 3 mg of peanut protein. Patients with severe symptoms had lower threshold doses compared with those of patients with mild symptoms (P =.027). CONCLUSIONS: A substantial part of a population with peanut allergy will react to very low amounts of peanut, requiring accurate declaration of peanut content in consumer products. This is even more important because patients with severe reactions react to lower doses than patients with mild symptoms.

Adolescent↗

PubMed2002

Assessment of protein allergenicity: studies in brown norway rats.

For the safety evaluation of genetically engineered crops, the potential allergenicity of the newly introduced protein(s) has become an important issue. There is, however, no universal and reliable test system for the evaluation of the allergic sensitizing ability of food proteins. Therefore, there is a growing interest in the development of animal models. This paper summarizes the results of a promising food allergy model developed in Brown Norway (BN) rats. The results demonstrate that BN rats can be sensitized via the relevant oral route of exposure. Daily gavage dosing of the animals with several food proteins, without the use of adjuvants, resulted in significant antigen-specific IgE responses. In addition, the profile of allergens recognized by the immune system of the BN rat, appeared comparable to the profile of allergens recognized by allergic humans. Besides oral sensitization, local and systemic immune-mediated effects, such as increased gastrointestinal permeability, decreased breathing frequency, and decreased blood pressure, could also be observed in the sensitized animals after an oral challenge. All together, these observations suggest that this BN rat model might provide a suitable animal model to study the allergenicity of food proteins in humans.

Allergens↗