RESUMO
Among 74 patients with an immediate hypersensitivity reaction (IHR) to iodinated contrast media (ICM), the rate of allergic patients confirmed by positive prick test or diluted intradermal test (IDT) was 8.1%. 12.5% of re-exposed patients had a recurrent IHR despite negative skin tests. Investigations on pure IDT to ICM and development of drug provocation test may provide additional safety nets to uncover recurrent ICM reactors. Agreements among allergists are needed to unify practices.
RESUMO
Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher rates in the RNA of highly allergenic legumes. Transcripts from peanut, soybean, sesame, and mite allergens contained a higher density of gaps than those of nonallergens. Allergen transcripts translate into proteins with a cationic carboxy terminus depleted in hydrophobic residues. In mice, recombinant TI variants of the peanut allergen Ara h 2, but not the canonical allergen itself, induced, without adjuvant, the production of anaphylactogenic specific IgE (sIgE), binding to linear epitopes on both canonical and TI segments of the TI variants. The removal of cationic proteins from bovine lactoserum markedly reduced its capacity to induce sIgE. In peanut-allergic children, the sIgE reactivity was directed toward both canonical and TI segments of Ara h 2 variants. We discovered 2 peanut allergens, which we believe to be previously unreported, because of their RNA-DNA divergence gap patterns and TI peptide amino acid composition. Finally, we showed that the sIgE of children with IgE-negative milk allergy targeted cationic proteins in lactoserum. We propose that it is not the canonical allergens, but their TI variants, that initiate sIgE isotype switching, while both canonical and TI variants elicit clinical allergic reactions.
Assuntos
Alérgenos/genética , Alérgenos/imunologia , Fabaceae/genética , Fabaceae/imunologia , Mudança da Fase de Leitura do Gene Ribossômico , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Albuminas 2S de Plantas/genética , Albuminas 2S de Plantas/imunologia , Adolescente , Anafilaxia/etiologia , Anafilaxia/imunologia , Animais , Antígenos de Plantas/genética , Antígenos de Plantas/imunologia , Arachis/genética , Arachis/imunologia , Bovinos , Criança , Pré-Escolar , Feminino , Variação Genética , Humanos , Soros Imunes/genética , Soros Imunes/imunologia , Imunoglobulina E/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Amendoim/etiologia , Hipersensibilidade a Amendoim/imunologia , Phaseolus/genética , Phaseolus/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Glycine max/genética , Glycine max/imunologia , Transcrição GênicaRESUMO
BACKGROUND: Oral immunotherapy (OIT) protects patients with IgE-mediated food allergies from food-induced allergic reactions due to accidental exposure and may improve their quality of life. This approach has never been evaluated for hazelnut, a major cause of food allergy in Europe. OBJECTIVE: To determine the proportion of hazelnut-desensitized patients after 6 months of OIT and to identify predictors of successful desensitization. METHODS: In a retrospective single-center study, we included patients younger than 18 years who underwent at least 6 months of hazelnut OIT for IgE-mediated allergy, defined by history of hypersensitivity reaction after hazelnut ingestion, positive hazelnut skin prick test result or specific IgE, and positive double-blind, placebo-controlled food challenge. Patients able to tolerate 1635 mg of hazelnut protein (â¼8 hazelnuts) were considered to be hazelnut desensitized. We determined the proportion of desensitized patients after 6 months of OIT, searched for associations between baseline variables and successful desensitization, and estimated the frequency and severity of OIT-related adverse reactions. RESULTS: One hundred patients were included (64% males; median age, 5 years). History of severe reactions was noted in 7% of cases. At 6 months, the proportion of desensitized patients was 34% (95% CI, 25-44). The median eliciting dose (defined as the amount of hazelnut protein provoking a hypersensitivity reaction during the double-blind, placebo-controlled food challenge) increased from 106 mg (interquartile range, 51-249) at baseline to 523 mg (interquartile range, 190-1635) after 6 months of OIT (P < .0001). With longer therapy, the proportion of desensitized patients increased. Using multivariate analysis, successful desensitization was associated with older age (odds ratio [OR], 1.5; 95% CI, 1.2-2.2), smaller hazelnut skin prick test wheal diameter (OR, 0.61; 95% CI, 0.4-0.8), lower hazelnut specific IgE level (OR, 0.86; 95% CI, 0.72-0.98), and absence of cashew allergy (OR, 0.42; 95% CI, 0.12-0.64). Adverse reactions occurred in 30% of patients; none were severe. CONCLUSIONS: In a cohort of 100 patients aged 3 to 9 years, our results show for the first time that hazelnut OIT is associated with hazelnut desensitization and may be safe in most patients undergoing this therapy.
