Common drugsCommon drugs containing PEG: laxatives, Gaviscon double action, depotcorticosteroids, for example methylprednisolone, Depo Provera, penicillin Importance of brand Depends on brand (checklist of excipients 6.1 on SmPC or contents 6 on PIL). PEG is also called macrogol PEG Molecular Weight Higher PEG MWs appear more allergenic, and molecular weight and amount of PEG determines whether an allergic reaction occurs Topical products Mild usually cutaneous reactions (pruritus, rhino-conjunctivitis) to cosmetics, toothpaste, mouthwashes, shower gels, moisturizers, hand sanitizers and soaps often with lower PEG molecular weights. Vaccine reaction Immediate-onset (minutes) severe systemic allergic reaction to an mRNA COVID−19 vaccine Abbreviations: MW, molecular weight; PEG, polyethylene glycol; SmPC, summary of product characteristics. TA B L E 1 The clinical features of a PEG-allergic patient may help identify at-risk patients before vaccination or if a COVID-19 vaccine reaction was likely due to PEG Key messages 1. The Pfizer/BioNTech COVID-19 vaccine can cause severe anaphylaxis of unknown cause 2. Here, we show polyethylene glycol allergy caused one of the first cases of anaphylaxis to the Pfizer/BioNTech COVID-19 vaccine 3. Allergy skin prick testing with polyethylene glycol triggered anaphylaxis, highlighting the importance of safety procedures during investigation | 863 RESEARCH LETTER
The role(s) of the novel stargazin-like ␥-subunit proteins remain controversial. We have shown previously that the neuron-specific ␥7 suppresses the expression of certain calcium channels, particularly Ca V 2.2, and is therefore unlikely to operate as a calcium channel subunit. We now show that the effect of ␥7 on Ca V 2.2 expression is via an increase in the degradation rate of Ca V 2.2 mRNA and hence a reduction of Ca V 2.2 protein level. Furthermore, exogenous expression of ␥7 in PC12 cells also decreased the endogenous Ca V 2.2 mRNA level. Conversely, knockdown of endogenous ␥7 with short-hairpin RNAs produced a reciprocal enhancement of Ca V 2.2 mRNA stability and an increase in endogenous calcium currents in PC12 cells. Moreover, both endogenous and expressed ␥7 are present on intracellular membranes, rather than the plasma membrane. The cytoplasmic C terminus of ␥7 is essential for all its effects, and we show that ␥7 binds directly via its C terminus to a heterogeneous nuclear ribonucleoprotein (hnRNP A2), which also binds to a motif in Ca V 2.2 mRNA, and is associated with native Ca V 2.2 mRNA in PC12 cells. The expression of hnRNP A2 enhances Ca V 2.2 I Ba , and this enhancement is prevented by a concentration of ␥7 that alone has no effect on I Ba . The effect of ␥7 is selective for certain mRNAs because it had no effect on ␣2␦-2 mRNA stability, but it decreased the mRNA stability for the potassium-chloride cotransporter, KCC1, which contains a similar hnRNP A2 binding motif to that in Ca V 2.2 mRNA. Our results indicate that ␥7 plays a role in stabilizing Ca V 2.2 mRNA.
Suspected anaphylaxis to the COVID-19 vaccines in the UK is reported at a rate of about 11-17 per million doses for the Pfizer/ BioNTech and AstraZeneca vaccines respectively [MHRA yellow card data, 23 June 2021]. This will underestimate the true size of the problem as cases are not reported and 43% of these data relate to second doses. However, after investigation, true allergy is rarely found and many are not IgE mediated 1 and are often labelled immunogenic reactions. Recent studies have shown successful revaccination in patients who had suspected allergic reactions to their first dose. 2,3 Polysorbate 80 (PS80) is the potentially allergenic excipient in the AstraZeneca and Janssen/Johnson and Johnson COVID-19 vaccines. PS80 is used as an excipient in many drugs (including some vaccines, e.g., some influenza vaccines) and as a food additive and is thus widely tolerated. 4 There have been cases of clinical reactivity
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