The TWEAK/Fn14 axis in anaphylactic shock

Galli, Stephen J.

doi:10.1016/j.jaci.2019.11.044

Cited by 2 publications

(3 citation statements)

References 11 publications

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“…IgE‐dependent anaphylaxis has been clearly characterized in humans 6 in food‐induced anaphylaxis. In contrast, IgE‐independent mechanisms (including those mediated by IgG, by the complement system, and direct activation of mast cells and basophils by drugs) have been studied in experimental animal models 7–10 and barely in humans 11,12 …”

Section: Introductionmentioning

confidence: 99%

“…In contrast, IgE-independent mechanisms (including those mediated by IgG, by the complement system, and direct activation of mast cells and basophils by drugs) have been studied in experimental animal models [7][8][9][10] and barely in humans. 11,12 The diagnosis is carried out at the time of the reaction and is always based on clinical symptoms. Therefore, it often depends on the qualifications and experience of the specialist that assesses the patient since objective biomarkers that fully discriminate an anaphylactic event do not exist.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers

Perales-Chordá

Obeso

Twomey

et al. 2021

Clin Experimental Allergy

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Background Despite the increasing incidence of anaphylaxis, its underlying molecular mechanisms and biomarkers for appropriate diagnosis remain undetermined. The rapid onset and potentially fatal outcome in the absence of managed treatment prevent its study. Up today, there are still no known biomarkers that allow an unequivocal diagnosis. Therefore, the aim of this study was to explore metabolic changes in patients suffering anaphylactic reactions depending on the trigger (food and/or drug) and severity (moderate and severe) in a real‐life set‐up. Methods Eighteen episodes of anaphylaxis, one per patient, were analysed. Sera were collected during the acute phase (T1), the recovery phase (T2) and around 2–3 months after the anaphylactic reaction (T0: basal state). Reactions were classified following an exhaustive allergological evaluation for severity and trigger. Sera samples were analysed using untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC‐MS) and proton nuclear magnetic resonance spectroscopy (1H‐NMR). Results ‘Food T1 vs T2’ and ‘moderate T1 vs T2’ anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food + drug or severe anaphylaxis. Moreover, the model of food anaphylaxis was able to distinguish the well‐characterized IgE (antibiotics) from non‐IgE‐mediated anaphylaxis (nonsteroidal anti‐inflammatory drugs), suggesting a differential metabolic pathway associated with the mechanism of action. Metabolic differences between ‘moderate vs severe’ at the acute phase T1 and at basal state T0 were studied. Among the altered metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. Conclusions The results of this exploratory study provide the first evidence that different anaphylactic triggers or severity induce differential metabolic changes along time or at specific time‐point, respectively. Besides, the basal status T0 might identify high‐risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers

Perales-Chordá

Obeso

Twomey

et al. 2021

Clin Experimental Allergy

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“…Our findings regarding their negative association with anaphylaxis expands their potential protective roles beyond airways allergic reactions to glutenin-induced life-threatening systemic anaphylaxis. Notably, the TWEAK R (Fn14) axis has been positively linked to anaphylaxis in previous mouse models of passive and active sensitization with adjuvant [53,54]. In this study, we demonstrate for the first time that TWEAK R is negatively linked to glutenin-induced active anaphylaxis in an adjuvantfree mouse model of food allergy.…”

Section: Discussionmentioning

confidence: 58%

Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis

Jorgensen,

Gao,

Arul Arasan

et al. 2023

IJMS

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Wheat is a prominent allergenic food that can trigger life-threatening anaphylaxis. Presently, it remains unclear whether wheat glutenin (WG) extract possesses inherent sensitization potential independently, without the use of adjuvants, and whether it can sensitize mice to the extent of inducing life-threatening systemic anaphylaxis. In this study, we tested the hypothesis that repeated skin exposures to WG extract without adjuvant will sensitize mice with the resultant anaphylactic reaction upon systemic WG challenge. Balb/c mice were bred and maintained on a strict plant protein-free diet and were repeatedly exposed to a WG extract or vehicle once a week for 9 weeks. WG-specific (s)IgE and total (t)IgE levels were quantified. Mice were challenged with WG extract to induce anaphylactic reactions as measured by hypothermic shock response (HSR) and mucosal mast cell degranulation response (MMCR). We also conducted proteomic analysis of 120 spleen immune markers. These skin-sensitized mice exhibited exposure-dependent IgE responses and near-fatal anaphylaxis upon challenge. Proteomic analysis identified seven dramatically elevated immune biomarkers in anaphylactic mice. These data reveal that WG is intrinsically allergenic, and that chronic skin exposure to WG extract can prime the mice for potentially fatal anaphylaxis.

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The TWEAK/Fn14 axis in anaphylactic shock

Cited by 2 publications

References 11 publications

Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers

Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers

Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis

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