BACKGROUNDPeanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS Randomization and BlindingEligible participants were randomly assigned, in a 3:1 ratio, to receive either AR101, a peanut-derived pharmaceutical product that was manufactured

Immunotherapy (IT) by injection more readily induces clinical tolerance to stinging insects than to respiratory allergens. However, while systemic immunization induces adaptive responses systemically, the induction of mucosal immunity generally requires local Ag exposure. Taken together, these observations suggest that the poor success rate of systemic IT for asthma could be a consequence of inadequate immune modulation in the airways. In support of this position, investigations presented in this report demonstrate that allergen IT more effectively induces airway allergen tolerance in Th2-sensitized mice, when delivered by the intranasal (i.n.) vs the intradermal (i.d.) route. Moreover, compared with native allergen, allergen immunostimulatory sequence oligodeoxynucleotide conjugate proved to be a more effective i.n. IT reagent for protecting allergic mice from airway hypersensitivity responses. Furthermore, for both native allergen and allergen immunostimulatory sequence oligodeoxynucleotide conjugate, i.n. and i.d. IT delivery were similarly effective in modulating systemic immune profiles in Th2-sensitized mice, while only i.n. IT had significant immunomodulatory activity on B and T cell responses in the airways. The present investigations may be the first to suggest that i.n. IT is more effective than i.d. IT for the treatment of asthma. Furthermore, our results suggest that modulating airway rather than systemic immunity may be the more important therapeutic target for the induction of clinical tolerance to respiratory allergens.

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We previously demonstrated that treatment of acute asthmatic rats with gene therapy using plasmid-encoding Galectin-3 (Gal-3) resulted in an improvement of cellular and functional respiratory parameters. The next question that we wanted to clarify was if in a chronic situation where the treated animal continues to inhale the Ag, does this procedure prevent the chronicity and the remodeling? Chronic inflammation was induced by intranasal administration of OVA over a period of 12 wk. In the treated group, the Gal-3 gene was introduced by intranasal instillation in 50 mul of plasmid-encoding Gal-3. Noninvasive airway responsiveness to methacholine was tested at different times. Cells were obtained by bronchoalveolar lavage and used for RNA extraction and cytometric studies. Eosinophils were counted in blood and bronchoalveolar lavage fluid. Real-time PCR was used to measure Gal-3 and cytokine mRNA expression in lung. Lungs were paraffined and histologic analyses were performed (H&E, periodic acid-Schiff, and Masson Trichrome stain). Our results showed that 12 wk after the first intranasal Ag instillation in chronically asthmatic mice, treatment with the Gal-3 gene led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion and subepithelial fibrosis in the chronically asthmatic mice, with a quantitatively measured reduction in lung collagen, a prominent feature of airway remodeling. Plasmid-encoding Gal-3 acts as a novel treatment for chronic asthma in mice producing nearly complete blockade of Ag responses with respect to eosinophil airway accumulation, airway hyperresponsiveness, and remodeling.

We evaluated the usefulness of individual tryptase levels and variations after adverse drug reactions in 64 patients. Our aim was to find a tool for the diagnosis of drug allergy. Thirty-seven subjects were confirmed to have drug allergy, 12 had nonsteroidal anti-inflammatory drug (NSAID) reactions, five had negative controlled drug challenges (NAAR), and 10 had symptoms after placebo intake (PLA). Serum tryptase levels greatly increased after anaphylactic shocks (2242%) and anaphylaxis (710.5%). Patients with allergic urticaria and those with idiosyncratic responses to acetylsalicylic acid (ASA) exhibited a small increase in serum tryptase (49.5% and 38.2%, respectively). In the other two groups (NAAR and PLA), no variation in this serum protease was observed. The time of appearance of the serum tryptase peak differed considerably among patients with similar clinical reactions (from 30 min to 6 h) and was independent of the latent period, severity of symptoms, or the amount of tryptase released. We conclude that serum tryptase determinations are helpful in the diagnosis of anaphylactic shock and anaphylaxis, but serial measurements may be needed to confirm mast-cell participation in milder reactions.