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Background: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. Methods: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. Results: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. Conclusion: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies.

Additional file 3. Consent Form (in German).

BackgroundThere is a need to support the diagnosis of anaphylaxis by objective markers. miRNAs are promising noncoding RNA species that may serve as serological biomarkers, but their use in diagnosing anaphylaxis has not been systematically studied to our knowledge. We aimed to comprehensively investigate serum biomarker profiles (proteins, lipids, and miRNAs) to support the diagnosis of anaphylaxis.MethodsAdult patients admitted to the emergency room with a diagnosis of anaphylaxis (3 hours) were included. Blood samples were taken upon emergency room arrival and 1 month later.ResultsNext-generation sequencing of 18 samples (6 patients with anaphylaxis in both acute and nonacute condition, for 12 total samples, and 6 healthy controls) identified hsa-miR-451a to be elevated during anaphylaxis, which was verified by quantitative real-time PCR in the remaining cohort. The random forest classifier enabled us to classify anaphylaxis with high accuracy using a composite model. We identified tryptase, 9α,11β-PGF2, apolipoprotein A1, and hsa-miR-451a as serological biomarkers of anaphylaxis. These predictors qualified as serological biomarkers individually but performed better in combination.ConclusionUnexpectedly, hsa-miR-451a was identified as the most relevant biomarker in our data set. We were also able to distinguish between patients with a history of anaphylaxis and healthy individuals with higher accuracy than any other available model. Future studies will need to verify miRNA biomarker utility in real-life clinical settings.FundingThis work is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) as part of the clinical research unit (CRU339): Food Allergy and Tolerance (FOOD@) (project number 409525714) and a grant to MW (Wo541-16-2, project number 264921598), as well as by FOOD@ project numbers 428094283 and 428447634.

Additional file 1. The SPIRIT Checklist.

Summary Background Acetylsalicylic acid (ASA) may cause difficult-to-treat symptoms of the airways, skin, or gastrointestinal tract in hypersensitive patients. Due to the chemical relationship between salicylic acid and ASA, a role of a low-salicylate diet has been discussed. Methods This review evaluates whether low salicylate diets are meaningful from an allergological or nutritional–physiological perspective. Results The body’s arachidonic acid metabolism plays a crucial role in the pathogenesis of ASA intolerance. Despite their chemical affinity, ASA and salicylic acid affect the arachidonic pathway differently. The intake of salicylic acid with food is low compared to therapeutic doses of ASA. There is increasing evidence that protective effects of a high fruit and vegetables diet is related in part to the intake of salicylates. In salicylate-low diets, fruit and vegetables are reduced, harboring the risk of an insufficient diet and malnutrition. Conclusion Dietary therapy in ASA-intolerant patients is not recommended.

Additional file 1. Questionnaire.

Background Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. Methods Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. Results The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. Conclusions Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more. Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged >= 65 (elderly) in comparison to data from adults (18-64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed. Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001). Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome.

Refractory anaphylaxis (unresponsive to treatment with at least two doses of minimum 300 μg adrenaline) is a rare and often fatal hypersensitivity reaction. Comprehensive data on its definition, prevalence, and risk factors are missing. Using the data from the European Anaphylaxis Registry (11,596 cases in total) we identified refractory anaphylaxis cases (n = 42) and analyzed these in comparison to a control group of severe anaphylaxis cases (n = 4,820). The data show that drugs more frequently elicited refractory anaphylaxis (50% of cases, p < 0.0001) compared to other severe anaphylaxis cases (19.7%). Cases elicited by insects (n = 8) were more often due to bees than wasps in refractory cases (62.5 vs. 19.4%, p = 0.009). The refractory cases occurred mostly in a perioperative setting (45.2 vs. 9.05, p < 0.0001). Intramuscular adrenaline (as a first line therapy) was administered in 16.7% of refractory cases, whereas in 83.3% of cases it was applied intravenously (significantly more often than in severe anaphylaxis cases: 12.3%, p < 0.0001). Second line treatment options (e.g., vasopression with dopamine, methylene blue, glucagon) were not used at all for the treatment of refractory cases. The mortality rate in refractory anaphylaxis was significantly higher (26.2%) than in severe cases (0.353%, p < 0.0001). Refractory anaphylaxis is associated with drug-induced anaphylaxis in particular if allergens are given intravenously. Although physicians frequently use adrenaline in cases of perioperative anaphylaxis, not all patients are responding to treatment. Whether a delay in recognition of anaphylaxis is responsible for the refractory case or whether these cases are due to an overflow with mast cell activating substances-requires further studies. Reasons for the low use of second-line medication (i.e., methylene blue or dopamine) in refractory cases are unknown, but their use might improve the outcome of severe refractory anaphylaxis cases.