Anaphylaxis, drug allergy, urticaria, and angioedemaPGE2 deficiency predisposes to anaphylaxis by causing mast cell hyperresponsiveness
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Section snippets
Anaphylaxis registry, data extraction, and analysis
The European Anaphylaxis Registry, which contains data from patients with anaphylactic reactions, has been covered by several publications.4,6,22 Serum samples from 48 patients with a history of Hymenoptera sting anaphylaxis were collected in 2010-2019. A group of 27 healthy subjects served as controls. Severity was classified according to anaphylaxis severity grade (Ring and Mesmer23), as based on the clinical reaction patterns of the most recent anaphylaxis episode (assessed before first aid
Patients with anaphylaxis are characterized by lower levels of PGE2
To test our hypothesis that low PGE2 level predisposes to severe allergic reactions, we analyzed sera from 48 patients with a history of Hymenoptera sting anaphylaxis for levels of PGE2 in comparison with the levels in 27 healthy donors. Patients with anaphylaxis indeed exhibited substantially lower levels of the lipid mediator (a mean level of 142.3 ± 14.11 pg/mL) compared with the controls (a mean level of 324.7 ± 33.73 pg/mL) (Fig 1, A). When only the group of patients with anaphylaxis was
Discussion
PGE2 is the most versatile and pleiotropic eicosanoid mediator.35, 36, 37 Studies in the past few decades have suggested a protective role of COX and PGE2 in the precipitation of allergic symptoms.38, 39, 40, 41 Our work on the anaphylaxis registry revealed COX inhibitors as facilitators of allergic responses; hence their classification as (extrinsic) cofactors.8
The aim of this study was to delineate whether the PGE2 network may have a more general role in anaphylaxis. We first demonstrated
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2023, Clinical Immuno-OncologyAn update on anaphylaxis and urticaria
2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Lower PGE2 levels and higher susceptibility to anaphylaxis were confirmed in mice of the black 6 inbred mouse strain C57BL/6 versus in mice of the albino inbred mouse strain Balb/c. The data suggest that homeostatic levels of PGE2 attenuate MC activation via the prostanoid receptors for PGE2 EP2/EP4 and protect against anaphylaxis.22,23 The classical biomarkers of anaphylaxis such as histamine or tryptase have limitations in clinical practice, and so far, they have not been established to differentiate among different phenotypes.
Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease
2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Of note, high levels of IL-4 within the tissues may be a direct cause of the reduction in COX-2 and PGE2 levels in AERD, as IL-4 can inhibit PGE2 production through selective inhibition of COX-2 mRNA,29,30 although the specific enzymatic pathways that were affected by dupilumab and led to the increase in PGE2 level are not yet clear. Deficient levels of PGE2 likely have a major role in AERD disease pathogenesis, as PGE2 signaling inhibits 5-lipoxygenase (5-LO) function, preventing the synthesis of cysLTs,31 and PGE2 also has direct protective effects on mast cells.32 Thus, the rise in nasal PGE2 levels and subsequent restoration of respiratory tissue levels of PGE2 that we observed with dupilumab treatment could contribute to the significant decrease seen in nasal and urinary LTE4 through suppression of mast cell activation and through 5-LO inhibition of cysLT-producing granulocytes (Fig 3, A and D).
Diversities of allergic pathologies and their modifiers: Report from the second DGAKI-JSA meeting
2022, Allergology InternationalAdvances in mast cell biology
2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Although PGE2 is thought to play a critical role in tenuously maintaining stabilization of airway MCs in patients with AERD,21 no previous studies examined its role in anaphylaxis. Using samples from patients enrolled in a European Anaphylaxis Registry, Rastogi et al22 demonstrated that serum levels of PGE2 in subjects presenting with hymenoptera anaphylaxis were significantly lower than in healthy controls, and correlated inversely with severity of reaction. The investigators also used a model of passive systemic anaphylaxis to demonstrate that C57BL/6 mice displayed greater reductions in core body temperature and lower serum levels of PGE2 than did BALB/c mice.
This work was supported by grants from the Deutsche Forschungsgemeinschaft to M.W. (WO 541/16-1 and 16-2).
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
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These authors shared the role of first author.
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These authors shared the role of senior author.