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Background: Previously, the protective farm effect was imitated using the whey protein beta-lactoglobulin (BLG) that is spiked with iron-flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin-iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model., Methods: Binding of iron-catechin into BLG was confirmed by spectroscopy and docking calculations. Serum IgE binding of children allergic or tolerating milk was assessed to loaded (holo-) versus empty (apo-) BLG and for human mast cell degranulation. BLG and Bet v 1 double-sensitized mice were orally treated with the holoBLG or placebo lozenge, and immunologically analysed after systemic allergen challenge. Human PBMCs of pollen allergic subjects were flow cytometrically assessed after stimulation with apoBLG or holoBLG using catechin-iron complexes as ligands., Results: One major IgE and T cell epitope were masked by catechin-iron complexes, which impaired IgE binding of milk-allergic children and degranulation of mast cells. In mice, only supplementation with the holoBLG lozenge reduced clinical reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen presentation. In allergic subjects, stimulation of PBMCs with holoBLG led to a significant increase of intracellular iron in circulating CD14+ cells with significantly lower expression of HLADR and CD86 compared to their stimulation with apoBLG., Conclusion: The FSMP lozenge targeted antigen presenting cells and dampened immune activation in human immune cells and allergic mice in an antigen-non-specific manner, thereby conferring immune resilience against allergic symptoms., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Elevation of the gastric pH increases the risk for sensitization against food allergens by hindering protein breakdown. This can be caused by acid-suppressing medication like sucralphate, H2-receptor blockers and proton pump inhibitors, as shown in recent murine experimental and human observational studies., Objective: The aim of the present study was to assess the sensitization capacity of the dietary supplement base powder and of over-the-counter antacids., Methods: Changes of the pH as well as of protein digestion due to base powder or antacids were measured in vitro. To examine the in vivo influence, BALB/c mice were fed codfish extract with one of the acid-suppressing substances. Read-out of antibody levels in the sera, of cytokine levels of stimulated splenocytes and of intradermal skin tests was performed., Results: The pH of hydrochloric acid was substantially increased in vitro by base powder as well as antacids in a time- and dose-dependent manner. This elevation hindered the digestion of codfish proteins in vitro. A significant increase in codfish-specific IgE antibodies was found in the groups fed codfish combined with Rennie Antacidum or with base powder; the latter also showed significantly elevated IgG1 and IgG2a levels. The induction of an anaphylactic immune response was proven by positive results in intradermal skin tests., Conclusions: Antacids and dietary supplements influencing the gastric pH increase the risk for sensitization against allergenic food proteins. As these substances are commonly used in the general population without consulting a physician, our data may have a major practical and clinical impact.

Background: One of the concerns of allergen-specific immunotherapy is the possible boost of inflammatory allergen-specific T lymphocytes. To address this problem, treatment with B cell epitopes devoid of allergen-specific T cell epitopes would be a promising alternative., Objective: In this study, we examined the therapeutic potency of a single mimotope, mimicking a structural IgE epitope of grass pollen allergen Phl p 5 in an established memory mouse model of acute allergic asthma., Methods: In the experimental set-up, BALB/c mice were primed with intraperitoneal injections of recombinant Phl p 5a (rPhl p 5a) and subsequently aerosol challenged with the nebulized allergen. Mice developed signs of bronchial asthma including hypereosinophilia around bronchi, goblet cell hyperplasia and enhanced mucus production., Results: When the mice were subsequently treated with the grass pollen mimotope coupled to keyhole limpet haemocyanin, bronchial eosinophilic inflammation and mucus hypersecretion decreased. Further, a decrease of Th2 cytokines IL-4 and IL-5 could be observed in the bronchoalveolar lavage (BAL). In contrast to rPhl p 5a, the mimotope was in vitro not able to stimulate splenocytes to proliferation or IL-5 production. Despite not affecting the levels of pre-existing IgE, vaccination with the single mimotope thus rendered anti-inflammatory effects in a mouse model of acute asthma., Conclusion: From our data, we conclude that vaccination with a mimotope peptide representing a single IgE epitope of the allergen Phl p 5a and being devoid of allergen-specific T cell epitopes is able to down-regulate inflammation in acute asthma.

Background: Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins., Objective: Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm., Methods: We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays., Results: Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo., Conclusion: Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.

Background: Recently we have shown that anti-acid drugs lead to an enhanced risk of food allergy. This may be due to hindered peptic digestion, caused by an elevation of the gastric pH. Additionally, it is known that aluminium-linked antigens lead to an increased probability of sensitization., Objective: Our aim in this study was to show whether sucralfate promotes sensitization not only by preventing peptic digestion but also by acting as a T-helper type 2 (Th2) adjuvant., Methods: To avoid the effect of sucralfate on the gastric pH and to show only the adjuvant effect, BALB/c mice were immunized on the parenteral route with codfish extract plus sucralfate, and control groups with aluminium hydroxide (alum) (Th2 adjuvant) or monophosphoryl lipid A (MPL) (Th1 adjuvant). Antigen-specific antibodies and cytokine levels were determined. The in vivo effect was investigated by intradermal skin tests., Results: Codfish-specific high IgG1 and IgE antibody levels as well as elevated IL-4 and IL-5 levels in alum- and MPL-treated mice, but more importantly also in sucralfate-treated mice, indicated a Th2 shift. Positive skin tests confirmed this Th2 response., Conclusions: Our data show that parenterally applied sucralfate is able to induce a Th2 response probably due to the aluminium content. This indicates that orally applied sucralfate may lead to an enhanced risk of food allergy not only by inhibiting peptic digestion but also by acting as a Th2 adjuvant.