Serological profiling reveals hsa-miR-451a as a possible biomarker of anaphylaxis

Francuzik, Wojciech; Pažur, Kristijan; Dalke, Magdalena; Dölle‐Bierke, Sabine; Babina, Magda; Worm, Margitta

doi:10.1172/jci.insight.156669

Cited by 18 publications

(19 citation statements)

References 61 publications

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“…Increased serum levels of miR-101-3p were observed also in neonatal sepsis ( 57 ). MiR-451a, mostly expressed in blood cells and released in extracellular vesicles, attenuates type I IFN and IL-6 responses ( 58 , 59 ) and was reported to progressively decrease with COVID-19 severity ( 19 – 21 ). MiR-155-5p plays a key role in the homeostasis and function of the immune system ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

et al. 2022

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BackgroundSARS-CoV-2 induces a spectrum of clinical conditions ranging from asymptomatic infection to life threatening severe disease. Host microRNAs have been involved in the cytokine storm driven by SARS-CoV-2 infection and proposed as candidate biomarkers for COVID-19.MethodsTo discover signatures of circulating miRNAs associated with COVID-19, disease severity and mortality, small RNA-sequencing was performed on serum samples collected from 89 COVID-19 patients (34 severe, 29 moderate, 26 mild) at hospital admission and from 45 healthy controls (HC). To search for possible sources of miRNAs, investigation of differentially expressed (DE) miRNAs in relevant human cell types in vitro.ResultsCOVID-19 patients showed upregulation of miRNAs associated with lung disease, vascular damage and inflammation and downregulation of miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis, and stress response. Compared with mild/moderate disease, patients with severe COVID-19 had a miRNA signature indicating a profound impairment of innate and adaptive immune responses, inflammation, lung fibrosis and heart failure. A subset of the DE miRNAs predicted mortality. In particular, a combination of high serum miR-22-3p and miR-21-5p, which target antiviral response genes, and low miR-224-5p and miR-155-5p, targeting pro-inflammatory factors, discriminated severe from mild/moderate COVID-19 (AUROC 0.88, 95% CI 0.80-0.95, p<0.0001), while high leukocyte count and low levels of miR-1-3p, miR-23b-3p, miR-141-3p, miR-155-5p and miR-4433b-5p predicted mortality with high sensitivity and specificity (AUROC 0.95, 95% CI 0.89-1.00, p<0.0001). In vitro experiments showed that some of the DE miRNAs were modulated directly by SARS-CoV-2 infection in permissive lung epithelial cells.ConclusionsWe discovered circulating miRNAs associated with COVID-19 severity and mortality. The identified DE miRNAs provided clues on COVID-19 pathogenesis, highlighting signatures of impaired interferon and antiviral responses, inflammation, organ damage and cardiovascular failure as associated with severe disease and death.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

et al. 2022

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“…Specifically, a study in a pediatric population with foodinduced anaphylaxis has shown increased circulating serum levels of miR-21-3p and miR-487b-3p [181]. Similarly, other evidences propose miR-451a as the most relevant biomarker in adult blood samples [88].…”

Section: Micrornasmentioning

confidence: 93%

“…Years later, those are considered a blend of prostaglandins and cysteinyl-leukotrienes released mainly through MC activation [35,86]. In addition, some of these molecules have been considered as valuable biomarkers in anaphylaxis [84,87,88]. Interestingly, non-steroidal anti-inflammatory drugs has been related with the increase of PGE2 and the production and overexpression of adenosine receptor 3 (A3) [89,90].…”

Section: Sphingosine-1-phosphate (S1pmentioning

confidence: 99%

“…Apolipoprotein B (ApoB) inversely correlates with severity in a pediatric population of food-induced anaphylaxis [170]. Moreover, the decrease of serum apolipoprotein AI (ApoAI) has been suggested as a good promising biomarker for this pathological event [88]. In addition, a drop in this protein and apolipoprotein E (ApoE) levels has also been reported in the serum of anaphylactic mice models and human patients.…”

Section: Circulating Proteinsmentioning

confidence: 99%

“…However, although this sampling is less invasive than blood collection, its sensitivity and specificity is much lower [53,56,57]. In addition, due to its stability both in urine and sera from anaphylactic patients, 9alpha,11beta-PGF2 appears to be a promising lipidic-derived biomarker of this pathological event [84,87,88]. Moreover, an exploratory study published recently point to the relevance of other altered metabolites in anaphylaxis.…”

Section: Metabolitesmentioning

confidence: 99%

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Anaphylaxis: Mediators, Biomarkers, and Microenvironments

Fernández-Bravo¹,

Palacio-Garcia²,

Requena-Robledo³

et al. 2022

J Investig Allergol Clin Immunol

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The life-threating nature of the anaphylactic reactions promotes a growing interest to discover new biomarkers that could support their better diagnosis and prevention. However, both the clinical features and the etiopathology of anaphylaxis are very diverse, hindering the elucidation of valuable molecular indicators of disease. Most studies of anaphylaxis have focused on the immune system. Precisely, anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and the release of several mediators. Among them, determinations of the serum tryptase levels is the main in vitro test used to confirm the reaction and there are no available biomarkers with predictive capacity for this pathological event. However, recent research has postulated that alternative pathways, cell types and systems are involved. Consequently, different molecular products have been explored and indicated as potential biomarkers, but none of them have been translated into the clinical practice yet. Precisely, vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs and metabolites have been found to be altered in patients with anaphylaxis. The recognition of biological processes and molecular pathways interacting in the magnitude of the microenvironments switched on in anaphylaxis will notably nourish the clinical practice and the recognition of better molecular markers. Therefore, this article covers a broad review of the different mediators described in anaphylaxis and their proposal as biomarkers of this pathological event, as well as their role in the molecular basis of the reaction.

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An interdisciplinary approach to characterize peanut‐allergic patients—First data from the FOOD@ consortium

Worm

Höfer

Birkner

et al. 2022

Clinical & Translational All

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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.

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Serological profiling reveals hsa-miR-451a as a possible biomarker of anaphylaxis

Cited by 18 publications

References 61 publications

Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

An interdisciplinary approach to characterize peanut‐allergic patients—First data from the FOOD@ consortium

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