Tamar Kinaciyan

Antacid medication inhibits digestion of dietary proteins and causes food allergy: A fish allergy model in balb/c mice

BACKGROUND Digestible proteins were supposed to be irrelevant for oral sensitization and induction of food allergy. Approximately 10% of the adult population uses antacids for the treatment of dyspeptic disorders, drugs that hinder peptic digestion. In these patients, proteins that are normally degradable might act as food allergens. OBJECTIVE We aimed to study the influence of antacid intake on the allergenicity of dietary proteins, taking sturgeon caviar and parvalbumin, the major fish allergen, as examples. METHODS Caviar proteins and recombinant parvalbumin from carp, rCyp c 1, were applied for intragastric feedings with or without the antacids sucralfate, ranitidine or omeprazole, using a Balb/c mouse model. RESULTS Both caviar proteins and parvalbumin were rapidly degraded in an in vitro digestion assay at pH 2.0, but not at pH 5.0, imitating the effect of antacids. The groups fed with caviar in combination with ranitidine hydrochloride intramuscularly or sucralfate orally had significant levels of caviar-specific IgE antibodies (P <.01), T-cell reactivity, and elevated counts of gastrointestinal eosinophils and mast cells. Food allergy in these groups was further evidenced by oral provocation tests and positive immediate-type skin reactivity. In contrast, feedings with caviar alone led to antigen-specific T-cell tolerance. None of the groups showed immune reactivity against the daily mouse diet. As a proof of the principle, feeding mice with parvalbumin in combination with ranitidine or omeprazole intramuscularly induced allergen-specific IgE antibodies (P <.05). CONCLUSIONS When antacid medication impairs the gastric digestion, IgE synthesis toward novel dietary proteins is promoted, leading to food allergy.

Premedication with Montelukast Reduces Local Reactions of Allergen Immunotherapy

Background: Local reactions (LRs) are a very frequent side effect of specific immunotherapy with allergens and can impair patients’ adherence. Antihistamine pretreatment – originally introduced as a safety measure to reduce anaphylactic side effects – has been the only treatment option for LRs so far, although these swellings usually do not appear immediately but after hours. We were interested whether pretreatment with the leukotriene antagonist montelukast would be better suited for preventing those reactions than pretreatment with the antihistamine desloratadine. Methods: Fifteen patients with a history of severe anaphylactic reactions to hymenoptera stings were enrolled into a prospective, double-blind, randomized, placebo-controlled pilot study. We selected a rush immunotherapy protocol consisting of 19 injections of hymenoptera venom administered over 5 consecutive days, where the majority is developing LRs, and counted the number of injections until an LR of >3 cm occurred. The patients were randomized to 3 treatment groups: premedication with placebo, 10 mg montelukast and 5 mg of the antihistamine desloratadine. Results: Compared with placebo, the occurrence of LRs (>3 cm) was significantly delayed by montelukast (p < 0.01, analysis of variance) but not by desloratadine (p = 0.19). The difference between montelukast and desloratadine was close to significant (p = 0.054). Itching, recorded on a scale from 0 to 5, did not differ between the 3 groups. Conclusion: Montelukast can be useful in the prevention of LRs after specific immunotherapy.

Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen with significant homology to ribosomal inactivating proteins.

Background Patients suffering from allergic rhinoconjunctivitis and dyspnoea during summer may exhibit these symptoms after contact with flowers or dietary products of the elderberry tree Sambucus nigra.

Mobile telephone as new source for nickel dermatitis

Nickel is widely known as the most relevant contact allergen, with sensitization rates up to 28.4% among young adults (1). Therefore, the ‘EU nickel directive’, introduced in 1994, tried to protect these patients from nickel-releasing consumer products for direct and prolonged contact with the skin (2). The only technical products mentioned in this 12-year-old directive are ‘wrist-watch cases, watch straps and tighteners’ (3).

Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model.

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.

Characterization of the human T cell response to antigen 5 from Vespula vulgaris (Ves v 5)

Background The T cell reactivity to the major allergen of bee venom, phospholipase A2, has been thoroughly characterized. In contrast, only little is known about the human cellular response to major allergens from wasp venom.

Allergologic exploration of germins and germin-like proteins, a new class of plant allergens

Background:  Germins and the related germin‐like proteins (GLPs) are glycoproteins expressed in many plants in response to biotic and abiotic stress. To test the potential impact of germins and GLPs, recombinant germin from Triticum aestivum (tGermin) and GLPs from Arabidopsis thaliana (tGLP), both produced in transformed tobacco plants, were used.

Malignancy and Specific Allergen Immunotherapy: The Results of a Case Series

Background: Specific immunotherapy with allergen is the only causative treatment for IgE-mediated allergies such as stinging insect allergy or hay fever and works by the induction of blocking antibodies and regulatory T lymphocytes. Objective: Does a hypothetical obstruction of tumor surveillance presupposing the induction of regulatory T cells really justify detaining immunotherapy to oncologic patients as suggested by recent guidelines? Methods: We report 6 patients (4 female, 2 male) suffering or having suffered from stage 1 cancer (4 melanomas, 1 lung cancer, 1 breast cancer) and concomitant IgE-mediated allergy. Four of them had a history of severe anaphylactic reactions to the insect yellow jacket, the 5th suffered from allergic rhinoconjunctivitis to dust mites, and the 6th to grass/rye pollen. Results: Between 2004 and 2010, subcutaneous immunotherapy was safely performed in 5 patients without signs of tumor reactivation. The cancer in 2 of them was diagnosed immediately after specific immunotherapy had been initiated and in another 2 the active cancer phase had already finished years before; the 5th suffered from a relapse around the time of the initiation of immunotherapy. At the time of the writing of the manuscript, 4 of them had already concluded 3 years of treatment, another one almost 1 year. The melanoma in the 6th patient was diagnosed 5 months after reaching the maintenance dose. Immunotherapy with grass/rye pollen was aborted in this patient based on current guidelines. Conclusions: Specific immunotherapy was safely administered in patients suffering concomitantly from IgE-mediated allergy and lower stage cancer.

Cloning of the Patatin–Like Latex Allergen Hev b 7, Its Expression in the Yeast Pichia pastoris and Its Immunological Characterization

The 43–kD latex allergen Hev b 7 was purified from the latex of Hevea brasiliensis and identified by N–terminal and internal peptide sequences as highly homologous to patatins. Patatins are storage proteins encoded by a multigene family found in plants such as potato and tomato. We have obtained a cDNA clone coding for a cytoplasmic form of Hev b 7. The recombinant protein was expressed in the methylotrophic yeast Pichia pastoris at 10 mg/l culture supernatant. Both natural Hev b 7 and rHev b 7 were recognized by IgE in 11% of the latex–allergic patients. rHev b 7 inhibited binding to its counterpart in natural rubber latex extracts. Purified rHev b 7 used at concentrations of 10 μg/ml in skin prick tests produced wheal–and–flare reactions of sizes equal to those produced by nHev b 7. Furthermore, we were able to show that rHev b 7 possessed esterase activity. A plant expression system for the production of larger quantities of recombinant latex allergens as an alternative to the preparation from H. brasiliensis sap is discussed.

Oral exposure to Mal d 1 affects the immune response in patients with birch pollen allergy

BACKGROUND Antibodies and T cells specific for the major birch pollen allergen Bet v 1 cross-react with structurally related food allergens, such as Mal d 1 in apple. OBJECTIVE We sought to evaluate the effects of oral uptake of Mal d 1 on the allergen-specific immune response in patients with birch pollen allergy. METHODS Patients received 50 μg of rBet v 1 sublingually on 2 consecutive days outside of the birch pollen season. One year later, equal amounts of rMal d 1 were administered. Blood samples were collected before and after oral exposure, as well as before and after the intermediate birch pollen season. Allergen-specific IgE levels were determined by using ImmunoCAP. Proliferation of allergen-stimulated PBMCs was assessed, as well as the expression of IL-5, IL-13, IL-10, IFN-γ, and forkhead box protein 3 (Foxp3) in isolated T cells (real-time PCR). Allergen-specific T-cell lines were analyzed for epitope recognition. RESULTS Orally administered Bet v 1 transiently reduced Bet v 1-specific serum IgE levels, as well as Bet v 1- and Mal d 1-induced T-cell proliferation, and enhanced the expression of IL-5, IL-10, and Foxp3. Orally applied Mal d 1 significantly decreased Bet v 1- and Mal d 1-specific IgE levels and induced IL-5 and IL-10 but no Foxp3 expression. In contrast to Bet v 1, Mal d 1 triggered IFN-γ production and T cells with a different epitope repertoire. Inhalation of birch pollen significantly enhanced allergen-specific IgE levels, T-cell proliferation, and IL-5, IL-10, IL-13, and Foxp3 expression. CONCLUSION Two sublingual administrations of 50 μg of Mal d 1 were well tolerated and induced transient immune responses seen during peripheral tolerance development. Thus recombinant Mal d 1 might be suitable and relevant for sublingual treatment of birch pollen-related apple allergy.