Abstract
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.
Highlights
Anaphylaxis is a type I hypersensitivity reaction that is potentially life-threatening if not adequately treated
We were able to distinguish between patients with a history of anaphylaxis and healthy individuals with higher accuracy than any other available model
Total mast cell tryptase is the only laboratory parameter routinely used for the diagnosis of anaphylaxis, but its moderate sensitivity and specificity require improvement
Summary
Anaphylaxis is a type I hypersensitivity reaction that is potentially life-threatening if not adequately treated. To more confidently administer adrenaline as the first-line treatment in cases where the elicitor of anaphylaxis is unknown and the diagnosis uncertain - there is a high medical need for objective laboratory parameters supporting the diagnosis of anaphylaxis (preferably using easy to acquire biological samples i.e., blood). Total mast cell tryptase is the only laboratory parameter routinely used for the diagnosis of anaphylaxis, but its moderate sensitivity and specificity require improvement (3). There is a need to support the diagnosis of anaphylaxis by objective markers. MiRNAs are promising non-coding RNA species that may serve as serological biomarkers, but their use in diagnosing anaphylaxis has not been systematically studied. We aimed to comprehensively investigate serum biomarker profiles (proteins, lipids, and miRNAs) to support the diagnosis of anaphylaxis
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