...positive responses to D pteronyssinus became negative in all patients with LAR when wortmannin was added to the assay (see Fig E1 in this article's Online Repository at www.jacionline.org). Since ...the first study of Huggins and Brostoff,8 several investigators have reported local production of IgE antibodies in patients with NAR.2,3 Others have shown that a percentage of patients with NAR respond to NPTs with allergens, being defined as having "local allergic rhinitis" or "entopy. ...BAT was able to diagnose at least 50% of cases of LAR to D pteronyssinus and was more sensitive than detection of nasal specific IgE and less time-consuming than NPTs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Scope
Chickpea (Cicer arietinum) allergy has frequently been reported particularly in Spain and India. Nevertheless, chickpea allergens are poorly characterized. The authors aim to identify and ...characterize potential allergens from chickpea.
Methods and Results
Candidate proteins are selected by an in silico approach or immunoglobuline E (IgE)‐testing. Potential allergens are prepared as recombinant or natural proteins and characterized for structural integrity by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE), circular dichroism (CD)‐spectroscopy, and mass spectrometry (MS) analysis. IgE‐sensitization pattern of Spanish chickpea allergic and German peanut and birch pollen sensitized patients are investigated using chickpea extracts and purified proteins. Chickpea allergic patients show individual and heterogeneous IgE‐sensitization profiles with extracts from raw and boiled chickpeas. Chickpea proteins pathogenesis related protein family 10 (PR‐10), a late embryogenesis abundant protein (LEA/DC‐8), and a vicilin‐containing fraction, but not 2S albumin, shows IgE reactivity with sera from chickpea, birch pollen, and peanut sensitized patients. Remarkably, allergenic vicilin, DC‐8, and PR‐10 are detected in the extract of boiled chickpeas.
Conclusion
Several IgE‐reactive chickpea allergens are identified. For the first time a yet not classified DC‐8 protein is characterized as minor allergen (Cic a 1). Finally, the data suggest a potential risk for peanut allergic patients by IgE cross‐reactivity with homologous chickpea proteins.
Chickpeas (Cicer arietinum) frequently can cause immunoglobuline E (IgE)‐mediated hypersensitivity reactions. However, chickpea allergens are poorly characterized. Using a molecular and biochemical methods, IgE‐reactive chickpea allergens are identified. Emphasizing the charcterization of a yet not classified DC‐8 protein as minor allergen (Cic a 1). Finally, data provide evidence for potential risk for peanut allergic patients by IgE‐cross‐reactivity with homologous chickpea proteins.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Increasing age is associated with severity and higher mortality of COVID‐19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more ...likely to die. We evaluated the association between relative telomere length (RTL) and COVID‐19 mortality. RTL was measured in patients hospitalized because of COVID‐19. We used Kaplan–Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID‐19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio HR (aHR) = 3.33; 95% confidence interval CI = 1.05–10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23–11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID‐19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Beta‐lactams generate different allergenic determinants that induce selective or cross‐reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the ...selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta‐lactams.
Methods
Prospective study evaluating children aged under 16 years reporting DHRs to beta‐lactams. Reactions were classified as immediate and non‐immediate reactions. The workup included sIgE, skin testing, and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for non‐immediate ones.
Results
Of the 510 children included, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%).
Among non‐immediate reactions (11.4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6–7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities.
Conclusions
There were few confirmed cases of either type of reaction. Skin testing proved less valuable in non‐immediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have non‐immediate reactions, while clavulanic acid selectivity was exclusive to the non‐immediate typology. Over half the cases with DPTs required 6–7 days of treatment for DHR confirmation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Purpose
Cross‐reactive hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAIDs) is a relatively common adverse drug event caused by two or more chemically unrelated drugs and ...that is attributed to inhibition of the COX activity, particularly COX‐1. Several studies investigated variations in the genes coding for COX enzymes as potential risk factors. However, these studies only interrogated a few single nucleotide variations (SNVs), leaving untested most of the gene sequence.
Experimental Approach
In this study, we analysed the whole sequence of the prostaglandin‐endoperoxide synthase genes, PTGS1 and PTGS2, including all exons, exon‐intron boundaries and both the 5′ and 3′ flanking regions in patients with cross‐reactive hypersensitivity to NSAIDs and healthy controls. After sequencing analysis in 100 case–control pairs, we replicated the findings in 540 case–control pairs. Also, we analysed copy number variations for both PTGS genes.
Key Results
The most salient finding was the presence of two PTGS1 single nucleotide variations, which are significantly more frequent in patients than in control subjects. Patients carrying these single nucleotide variations displayed a significantly and markedly lower COX‐1 activity as compared to non‐carriers for both heterozygous and homozygous patients.
Conclusion and Implications
Although the risk single nucleotide variations are present in a small proportion of patients, the strong association observed and the functional effect of these single nucleotide variations raise the hypothesis of genetic susceptibility to develop cross‐reactive NSAID hypersensitivity in individuals with an impairment in COX‐1 enzyme activity.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The presence of SARS‐CoV‐2 RNA in plasma has been linked to disease severity and mortality. We compared RT‐qPCR to droplet digital PCR (ddPCR) to detect SARS‐CoV‐2 RNA in plasma from ...COVID‐19 patients (mild, moderate, and critical disease).
Methods
The presence/concentration of SARS‐CoV‐2 RNA in plasma was compared in three groups of COVID‐19 patients (30 outpatients, 30 ward patients and 30 ICU patients) using both RT‐qPCR and ddPCR. Plasma was obtained in the first 24h following admission, and RNA was extracted using eMAG. ddPCR was performed using Bio‐Rad SARS‐CoV‐2 detection kit, and RT‐qPCR was performed using GeneFinder™ COVID‐19 Plus RealAmp Kit. Statistical analysis was performed using Statistical Package for the Social Science.
Results
SARS‐CoV‐2 RNA was detected, using ddPCR and RT‐qPCR, in 91% and 87% of ICU patients, 27% and 23% of ward patients and 3% and 3% of outpatients. The concordance of the results obtained by both methods was excellent (Cohen's kappa index = 0.953). RT‐qPCR was able to detect 34/36 (94.4%) patients positive for viral RNA in plasma by ddPCR. Viral RNA load was higher in ICU patients compared with the other groups (P < .001), by both ddPCR and RT‐qPCR. AUC analysis revealed Ct values (RT‐qPCR) and viral RNA load values (ddPCR) can similarly differentiate between patients admitted to wards and to the ICU (AUC of 0.90 and 0.89, respectively).
Conclusion
Both methods yielded similar prevalence of RNAemia between groups, with ICU patients showing the highest (>85%). RT‐qPCR was as useful as ddPCR to detect and quantify SARS‐CoV‐2 RNAemia in plasma.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in drug hypersensitivity reactions through mechanisms that may involve genetic predisposition. We performed a ...fine-mapping GWAS in patients with NSAID-induced hypersen-sitivity reactions with cross-intolerance belonging to the group of NSAID-induced urticaria, angioedema, and anaphylaxis (NIUAA) (2) and matched controls from South Spain, and we replicated the re-sults in patients and paired controls from central Spain. GNAI2 was a significant predictor of NSAID-induced hypersensitivity reactions. This association may reflect its influence on the activation of leukot-riene receptors and the recruitment of immune cells involved in the pathological mechanisms of NSAID hypersensitivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading cause of hypersensitivity drug reactions. The different chemical structures, cyclooxygenase 1 (COX-1) and/or COX-2 inhibitors, are taken ...at all ages and some can be easily obtained over the counter. Vasoactive inflammatory mediators like histamine and leukotriene metabolites can produce local/systemic effects. Responders can be selective (SR), IgE or T-cell mediated, or cross-intolerant (CI). Inhibition of the COX pathway is the common mechanism in CI, with the skin being the most frequent organ involved, followed by the lung and/or the nose. An important number of cases have skin and respiratory involvement, with systemic manifestations ranging from mild to severe anaphylaxis. Among SR, this is the most frequent entity, often being severe. Recent years have seen an increase in reactions involving the skin, with many cases having urticaria and/or angioedema in the absence of chronic urticaria. Aspirin, the classical drug involved, has now been replaced by other NSAIDs, with ibuprofen being the universal culprit. For CI, no in vivo/in vitro diagnostic methods exist and controlled administration is the only option unless the cases evaluated report repetitive and consistent episodes with different NSAIDs. In SR, skin testing (patch and intradermal) with 24-48 reading can be useful, mainly for delayed T-cell responses. Acetyl salicylic acid (ASA) is the test drug to establish the diagnosis and confirm/exclude CI by controlled administration. Desensitization to ASA has been extensively used in respiratory cases though it can also be applied in those cases where it is required.
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