Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans

Schöll, Isabella; Untersmayr, Eva; Bakos, Noémi; Roth‐Walter, Franziska; Gleiß, Andreas; Boltz‐Nitulescu, George; Scheiner, Otto; Jensen‐Jarolim, Erika

doi:10.1093/ajcn/81.1.154

Cited by 139 publications

(128 citation statements)

References 34 publications

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“…We have shown previously that anti-acid treatment is an important factor for induction of food-specific IgE in adult humans (5) and in mouse models (4,11). These anti-acid medications are also used as first-line drug treatment for up to 50% of pregnant women (15).…”

Section: Discussionmentioning

confidence: 99%

“…For the adult population, we could show in previous studies that the risk to develop sensitization against food allergens increases with the usage of acid-suppressing drugs (4,5), which are applied for the treatment of dyspeptic disorders such as gastric reflux, heartburn, and gastritis. We suggested that the hindered peptic digestion due to the elevated pH in the stomach leaves bigger fragments of alimentary proteins.…”

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confidence: 99%

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Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Schöll¹,

Ackermann²,

Özdemir

et al. 2007

FASEB j.

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The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1-and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. Keywordssensitization against food; sucralfate; digestion; children; lactation The incidence of food allergies has been steadily increasing in the past decades and these allergies now affect ~3.5-4% of the adult population in the United States(1) and ~2.2-5.5% of children in the first year of life (2). Apart from several environmental influence factors, no genuine explanation accounts for this high number of children with food sensitization. It is known that the risk for sensitization in the offspring is higher when one or both parents, but especially when the mother is atopic (3). This may be due to hereditary factors, but an atopic mother may also transfer factors that directly bias the immune response of the infant to an allergic phenotype. For the adult population, we could show in previous studies that the risk to develop sensitization against food allergens increases with the usage of acid-suppressing drugs (4, 5), which are applied for the treatment of dyspeptic disorders such as gastric reflux, heartburn, and gastritis. We suggested that the hindered peptic digestion due to the elevated pH in the stomach leaves bigger fragments of alimentary proteins. These proteins could then elicit allergy due to persistence of their native conformation. © FASEBApproximately two-thirds of pregnant women suffer from heartburn and reflux due to low esophageal sphincter pressure, which is caused by changes of the hormone status (6). For their treatment, Richter suggested a step-up algorithm beginning with lifestyle modifications and dietary changes. As the first-line medical treatment antacids and sucralfate are used (7). The same review states that actually ~30-50% of women use antacids to relieve heartburn and other acid-reflux symptoms during pregnancy. For sucralfate, another nonabsorbable drug like antaci...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Schöll¹,

Ackermann²,

Özdemir

et al. 2007

FASEB j.

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“…While Ara h 1 does not need to survive the digestion process as an intact protein or as large fragments to react with the immune system for induction of a specific immune response, this could still be the case for other food allergens. Previous studies examining the influence of digestion on the allergenic potential of other food proteins have revealed digestion to be an effective approach for a significant impairment of sensitization 35,36 and IgE-binding capacity. 35,37,38 We have previously shown that mixtures of peptides smaller than 2−5 kDa, which was generally thought to be the lower size limit for a peptide with inherent sensitizing capacity, 31 may still act as a "complete" allergen, 39 being able to sensitize, elicit allergic reaction, and react with IgE.…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

Digested Ara h 1 Loses Sensitizing Capacity When Separated into Fractions

Bøgh

Barkholt²,

Rigby

et al. 2012

J. Agric. Food Chem.

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The major peanut allergen Ara h 1 is an easily digestible protein under physiological conditions. The present study revealed that pepsin digestion products of Ara h 1 retained the sensitizing potential in a Brown Norway rat model, while this sensitizing capacity was lost by separating the digest into fractions by gel permeation chromatography. Protein chemical analysis showed that the peptide composition as well as the aggregation profiles of the fractions of Ara h 1 digest differed from that of the whole pool. These results indicate that the sensitizing capacity of digested Ara h 1 is a consequence of the peptides being in an aggregated state resembling the intact molecule or that most peptides of the digests need to be present in the same solution, having a synergistic or adjuvant effect and thereby augmenting the immune response against other peptides.

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“…On the other hand, anti-OVA IgG1 antibody was detected in serum of most of the OVA/E+SA mice with marked induction (Table 1). Interestingly it has been reported that although oral administration of allergenic hazelnut alone did not sensitize BALB/c mice, oral hazelnut with an antiulcer drug, omeprazole, sensitized mice with induction of hazelnut-specifi c IgG1 but not IgE, leading to immediate hypersensitive skin reactions (Schöll et al, 2005). In the OVA/E and OVA/E+SA groups, a similar increase of plasma histamine mediating IgE-dependent anaphylaxis was seen, but anaphylaxis was manifested more severely in the OVA/E+SA group than in the OVA/E group.…”

Section: Discussionmentioning

confidence: 99%

Effective induction of oral anaphylaxis to ovalbumin in mice sensitized by feeding of the antigen with aid of oil emulsion and salicylate

et al. 2012

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INTRODUCTIONThe potential allergenicity of novel proteins introduced into genetically engineered crops and that of proteins generated during the biotechnological process of food production is an important issue for the evaluation for safety of the food crops and products. Many approaches for assessing the allergenicity of such proteins have been proposed; these can be broadly classified into four areas, namely, the analysis of protein structure to predict allergenicity, serum screening of allergic proteins, new animal models, and proteomics (Selgrade et al., 2009;Ahuja et al., 2010).The biochemical approaches for the assessment of allergenic proteins are grounded on comparisons of the serologic identity of the novel protein with human allergens, taking into account factors such as structural similarity, amino acid sequence homology, resistance to proteolytic digestion in a simulated gastric fluid, and immunochemical reactivity with serum of subjects with allergy (Ladics, 2008). Although such investigations provide important information, they do not directly assess the inherent sensitizing potential of proteins. Animal models of food allergy are required for evaluating the sensitizing potential of allergenic proteins and to investigate mechanisms of food allergy. It is generally recognized that it is hard to reproduce food allergy in animals by oral feeding of a model allergenic protein at ABSTRACT -It is important to evaluate the ability of novel proteins in food crops and products to elicit potentially harmful immunologic responses, including allergic hypersensitivity. We developed a novel mouse model of food allergy involving an oral challenge of a protein antigen after feeding of the antigen in combination with modulating factors often ingested in daily life, namely, dietary oil emulsion and salicylate. In the model, BALB/c mice were sensitized orally for three weeks with ovalbumin (OVA) in linoleic acid/lecithin emulsion, followed immediately by intraperitoneal injection of sodium salicylate. At the end of the sensitization, the incidence of mice positive for serum OVA-specific IgG1 but not IgE had significantly increased in the combined-sensitization group. After the 3-week sensitization, a single or double oral challenge with OVA effectively and significantly caused severe anaphylaxis, as compared with the groups sensitized with OVA in the emulsion or the vehicle alone. Moderate increase of plasma histamine and intestinal abnormality in histology was found only in the combined-sensitization group. Anaphylaxis symptoms in the sensitized mice were induced more by oral challenge than by intravenous challenge, suggesting a critical role for the mucosal system. This is the first model for successful induction of oral anaphylaxis in mice sensitized by feeding of food protein without adjuvant. It will be useful to elucidate the mechanism of food allergy and to detect modulating factors of oral allergy at sensitization using this model, which simulates real life conditions.

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Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans

Abstract: Our experimental and epidemiologic data suggest that the intake of antiulcer drugs may lead to the induction of immediate-type food hypersensitivity toward hazelnut.

Cited by 139 publications

References 34 publications

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Digested Ara h 1 Loses Sensitizing Capacity When Separated into Fractions

Effective induction of oral anaphylaxis to ovalbumin in mice sensitized by feeding of the antigen with aid of oil emulsion and salicylate

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