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• W2031393112 abstract "To the Editor: The absorption of dietary protein is important in the development and elicitation of food-induced allergic reactions. Eighty years ago, it was suggested that undigested egg proteins were absorbed in human subjects.1Wilson S.J. Walzer M. Absorption of undigested proteins in human beings. IV Absorption of unaltered egg protein in infants and in children.Am J Dis Child. 1935; 50: 49-54Crossref Google Scholar Subsequent investigations have demonstrated absorption of intact dietary proteins, including food allergens, in the human circulation after ingestion.2Husby S. Jensenius J.C. Svehag S.E. Passage of undegraded dietary antigen into the blood of healthy adults. Quantification, estimation of size distribution, and relation of uptake to levels of specific antibodies.Scand J Immunol. 1985; 22: 83-92Crossref PubMed Scopus (155) Google Scholar The absorption fraction is largely unknown, but approximately 50 ppm of the ingested dose has been estimated.3Paganelli R. Levinsky R.J. Solid phase radioimmunoassay for detection of circulating food protein antigens in human serum.J Immunol Methods. 1980; 37: 333-341Crossref PubMed Scopus (57) Google Scholar Absorption of food proteins can take hours, but systemic reactions occurring in less than 30 minutes are common among individuals with food allergy.4Wensing M. Penninks A.H. Hefle S.L. Koppelman S.J. Bruijnzeel-Koomen C.A. Knulst A.C. The distribution of individual threshold doses eliciting allergic reactions in a population with peanut allergy.J Allergy Clin Immunol. 2002; 110: 915-920Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar We therefore aimed at investigating the absorption and kinetics of allergenic peanut proteins and a possible local uptake from the oral cavity in healthy adults. The study was approved by the local ethical committee (KF 01-081/01). Blood samples were drawn from individuals who had ingested peanuts. All had negative case histories for peanut allergy and negative skin prick test responses and specific IgE assay results for peanuts, soy, and pollen, and all had fasted 8 hours before peanut intake. The allergenic activity of absorbed peanut in serum was detected by means of histamine release (HR) from passively sensitized basophils.5Poulsen L.K. Pedersen M.H. Platzer M. Madsen N. Sten E. Bindslev-Jensen C. et al.Immunochemical and Biological Quantification of Peanut Extract.Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M. 2003; 94: 97-105PubMed Google Scholar In brief, Lymphoprep-isolated mononuclear cells (specific density: 1.077) (Nycomed, Oslo, Norway) containing 1% to 2% basophils were obtained from buffy coat bank blood with an anti-IgE–induced HR of greater than 30% and no response to peanut. These donor cells were stripped of cell-bound IgE and subsequently sensitized with serum from a patient with peanut allergy (verified on the basis of double-blind placebo-controlled peanut challenge, HR, skin prick test, and specific IgE level of 136 kUA/L; Pharmacia CAP system). The specificity of HR was confirmed by the absence of peanut-induced HR from basophils when sensitized with serum from nonallergic individuals. The HR standard curve was made by using an extract of 4 peanut species (raw peanut, stock solution of 6.4 mg protein/mL) subsequently diluted in nonallergic serum. Standard or serum samples (50% diluted) from the indicated time points were incubated with sensitized basophils, and the released histamine was determined by means of fluorometric analyses and expressed as the percentage of the total cellular histamine content. A release of greater than 10% was considered positive, and the assay sensitivity was 5 pg of peanut protein per milliliter of serum. Experiment 1a. Ten individuals (5 female patients; median age, 25 years) ingested 100 g of raw peanut, and blood was drawn at 0, ½, 1, 2, 3, 4, 5, and 24 hours. Peanut allergens were detected in the serum of 8 of 10 individuals (Fig 1, A), as demonstrated by a significant increase in HR 30 minutes to 5 hours after ingestion that peaked at 3 hours but with a considerable interindividual variation in the amount of absorbed peanut allergen. Experiment 1b. One individual (male; age, 36 years) ingested 5 different amounts (1-100 g) of raw peanut weekly, and blood was drawn at the indicated intervals (Fig 1, B). Detection of peanut allergens was possible from as early as 10 minutes to 24 hours after ingestion of 3.5 to 100 g, with a rough relationship between ingested dose and biologic activity. The 35 g dose appeared to produce larger biologic activity than 100 g, indicating a lack of a linear relationship in either uptake or detection system. Because absorption was measurable within 10 minutes after ingestion, a possible preintestinal uptake was investigated in experiment 2. Experiment 2. Six individuals chewed 10 g of raw peanuts for 2 minutes, followed by spitting out the food and rinsing their mouths with water. The individuals were instructed not to swallow any of the chewed peanuts and saliva. Blood was drawn, and allergenic activity was measured (Fig 2). A significant increase in HR was observed already at 10 minutes. To our knowledge, this is the first time that absorption of allergenic proteins has been studied by using a biologic test. Because the HR does not display a linear relationship between allergen concentration and mediator release, we attempted to quantify the absorbed peanut proteins in the serum by means of ELISA, but this was 10 times less sensitive than HR and was only able to detect peanut antigen in a minority of the samples. Interestingly, a similar HR response was observed when, for example, 35 and 100 g were ingested (Fig 1, B). This probably reflects the fact that HR has reached its maximum at 50% to 60%. Because no titration was performed, it is not possible to differentiate between these highly positive sera. More quantitative data for pharmacokinetic calculations of the area under the curve would be needed for estimation of the total absorbed amount, but this was not possible with a biologic test such as HR. It should be emphasized that HR measures biologic activity (ie, IgE cross-linking), which might still be possible for partly digested proteins. Our findings demonstrated allergen absorption from the buccal mucosa, which might explain the early onset of many systemic reactions. We chose peanut for this study because it is an important food allergen, but differences in uptake could explain the variances in allergenicity seen among different foods. A generalization of our results therefore awaits studies of other foods. Moreover, it is possible that patients with food allergy, in comparison with nonallergic individuals, have different absorption rates or that a local allergic inflammation might itself change the absorption rate. C. G. Dirks performed the experiments and data analysis and drafted the manuscript. M. H. Pedersen developed the peanut extract. M. H. Platzer and P. S. Skov assisted in the experimental design and data analysis. P. S. Skov and L. K. Poulsen designed the study and contributed to the final manuscript. C. Bindslev-Jensen designed the study and provided serum from a patient with verified peanut allergy." @default.
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• W2031393112 title "Does absorption across the buccal mucosa explain early onset of food-induced allergic systemic reactions?" @default.
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