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Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer. [ABSTRACT FROM AUTHOR]

This article discusses a study that explores the use of Toll-like receptor ligands (TLR-L) in combination with amoxicillin (AX) to increase the sensitivity of the basophil activation test (BAT) for detecting hypersensitivity reactions to AX. The results of the study suggest that this approach may be useful in detecting AX hypersensitivity reactions. However, further research is needed to understand the function of TLR-L and activation pathways in basophils. The study found that lipopolysaccharide (LPS) combined with AX was the most effective in activating basophils in patients with antibiotic allergies, but the effects varied among different patient groups. [Extracted from the article]

The article discusses the challenges in diagnosing and managing allergies to nonspecific lipid transfer protein (nsLTP) and the varying degrees of clinical severity in patients. A study was conducted to determine the minimum amount of peach nsLTP required to induce an allergic reaction during a food challenge test. The research found that around 24.5 μg of Pru p 3 (equivalent to 2.5 g of peach with peel) was needed to trigger symptoms, highlighting the importance of standardizing diagnostic tests for better clinical management. The study also emphasized the safety of the double-blind placebo-controlled food challenge procedure and its implications for improving patient quality of life. [Extracted from the article]

Immediate drug hypersensitivity reactions (IDHRs) are a burden for patients and the health systems. This problem increases when taking into account that only a small proportion of patients initially labelled as allergic are finally confirmed after an allergological workup. The diverse nature of drugs involved will imply different interactions with the immunological system. Therefore, IDHRs can be produced by a wide array of mechanisms mediated by the drug interaction with specific antibodies or directly on effector target cells. These heterogeneous mechanisms imply an enhanced complexity for an accurate diagnosis and the identification of the phenotype and endotype at early stages of the reaction is of vital importance. Currently, several endophenotypic categories (type I IgE/non‐IgE, cytokine release, Mast‐related G‐protein coupled receptor X2 (MRGPRX2) or Cyclooxygenase‐1 (COX‐1) inhibition and their associated biomarkers have been proposed. A precise knowledge of endotypes will permit to discriminate patients within the same phenotype, which is crucial in order to personalise diagnosis, future treatment and prevention to improve the patient's quality of life. [ABSTRACT FROM AUTHOR]

Background: Amoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE‐mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high‐risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta‐lactams, although controversy exists regarding the best activation marker. We have performed a real‐life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs. Methods: We prospectively evaluated patients with a clinical suspicion of immediate reactions after AX or AX‐CLV administration during a 6‐year period. The allergological work‐up was done following the EAACI recommendations. BAT was performed in all patients using CD63 and CD203c as activation markers. Results: In AX‐allergic patients, both activation markers, CD63 and CD203c, showed similar SE values (48.6% and 46.7%, respectively); however, specificity was of 81.1% and 94.6%, respectively, with CD203c showing good positive predictive value and like‐hood ratio. In CLV‐allergic patients, CD203c showed higher SE (50%) than CD63 (42.9%), maintaining the same value of SP (80%). Combining the results of both markers can slightly increase the sensitivity (51.4% for AX and 54.8% for CLV), although decreasing the specificity (79.7% and 73%, respectively). Interestingly, all patients with an anaphylactic shock showed a positive BAT to CLV using CD203c. Conclusions: BAT using CD203c showed a good confirmatory power, especially for AX allergy. Placing BAT as a first step in the diagnostic procedure can help reduce the need of performing a complete allergological work‐up in 46.6% of patients, diminishing the risk of reinducing allergic reactions. [ABSTRACT FROM AUTHOR]

Lactococcus lactis-derived microparticles ad mixed with allergen shift immune responses towards a regulatory profile in tree-nut allergic patients Proliferation and cytokine production from supernatant or proliferating cells data after stimulation with TBP alone did not show any significant changes in tree-nut-AP and HC (Figures S4A-C and S6A-C). Sublingual immunotherapy (SLIT) is a disease-modifying intervention that offers a potential long-lasting therapeutic effect in food allergy (FA). [Extracted from the article]

Background: The involvement of allergen‐specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC‐DP) in mucosal and peripheral B‐cell subpopulations in LAR patients. Methods: Nine LAR, 5 allergic rhinitis (AR), and 5 non‐atopic healthy control (HC) individuals were subjected to a 3‐day NAC‐DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera. Results: NAC‐DP induced an increase in IgE+CD38+ plasmablasts in the nasal mucosa of LAR patients, but not in AR or HC individuals. Markers of sequential recombination to IgE (εCSR) (from IgG) were observed in 33% of LAR, 20% of AR, and 0% of HC subjects. NAC‐DP increased the proportion of peripheral CD19+CD20+CD38+ plasmablasts in AR and LAR patients, but not in HC. Expression of the mucosal homing receptor CXCR3 in peripheral CD19+CD20+CD38+ plasmablasts from LAR, AR, and HC individuals was 7%, 5%, and 0.5%, respectively. In vitro DP stimulation increased proliferating CD19+CD20+CD38+ plasmablasts in LAR and AR patients, but not in HC. Serum DP‐sIgG was higher in LAR and AR patients as compared to HC. BAT was positive in 33%, 100%, and 0% of LAR, AR, and HC subjects, respectively. Conclusion: These results suggest that allergen exposure induces the sequential εCSR of IgG+CD19+CD20+CD38+ plasmablasts in the nasal mucosa of LAR patients. [ABSTRACT FROM AUTHOR]

Background: mRNA‐based COVID‐19 vaccines have been reported to induce hypersensitivity reactions (HSR) in a small number of individuals. We aimed to evaluate the real‐world incidence of the BNT162b2 mRNA COVID‐19 vaccine HSR and to determine the value of the basophil activation test (BAT) in the allergological workup of patients reporting these reactions. Methods: We prospectively enrolled patients with a clinical history indicative of HSR to the BNT162b2 mRNA COVID‐19 vaccine. The allergological workup included skin testing (STs) and BAT with polyethylene glycol (PEG) and the vaccine. In those with negative allergy assessments, the administration of the second dose of the BNT162b2 mRNA COVID‐19 vaccine was offered. Results: Seventeen adults were included. Eleven cases (64.7%) tested negative in the allergological workup and tolerated the re‐administration of the second dose of the vaccine and considered non‐allergic. Six cases (35.3%) were considered allergic and classified into three groups: 2 subjects displayed positive STs and/or BAT to PEG (Group A), two individuals displayed positive BAT to the vaccine (Group B), and in 2 patients with moderate or severe reactions, the culprit was not identified, tested negative to STs and BAT to both PEG and vaccine (Group C). We further evaluated the value of BAT when the results were positive to the vaccine and negative to PEG by performing BAT in controls groups, finding positive BAT results in 50% of controls, all of them recovered from COVID‐19 infection. In contrast, BAT was negative in patients who had not suffered from COVID‐19 disease. Conclusions: BAT can be used as a potential diagnostic tool for confirming allergy to PEG excipient but not to the vaccine as a positive result in BAT may indicate a past COVID‐19 infection instead of an allergy. [ABSTRACT FROM AUTHOR]

Background: Nonimmediate (delayed)‐allergic reactions to penicillins are common and some of them can be life‐threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods: Using next‐generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results: The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37–23.32; p <.0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838 genetic variants of the HLA‐DRB3 genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06–1.92; p =.001), but not immediate hypersensitivity. Conclusion: We showed that the HLA‐DRB3 locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of HLA‐DRB3*02:02 alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins. [ABSTRACT FROM AUTHOR]

The immunological mechanisms involved in drug hypersensitivity reactions (DHRs) are complex, and despite important advances, multiple aspects remain poorly understood. These not fully known aspects are mainly related to the factors that drive towards either a tolerant or a hypersensitivity response and specifically regarding the role of B and T cells. In this review, we focus on recent findings on this knowledge area within the last 2 years. We highlight new evidences of covalent and non‐covalent interactions of drug antigen with proteins, as well as the very first characterization of naturally processed flucloxacillin‐haptenated human leukocyte antigen (HLA) ligands. Moreover, we have analysed new insights into the identification of risk factors associated with the development of DHRs, such as the role of oxidative metabolism of drugs in the activation of the immune system and the discovery of new associations between DHRs and HLA variants. Finally, evidence of IgG‐mediated anaphylaxis in humans and the involvement of specific subpopulations of effector cells associated with different clinical entities are also topics explored in this review. All these recent findings are relevant for the underlying pathology mechanisms and advance the field towards a more precise diagnosis, management and treatment approach for DHRs. [ABSTRACT FROM AUTHOR]

Immediate allergic reactions to cephalosporins: Evaluation of cross-reactivity with a panel of penicillins and cephalosporins. Cephalosporins are, after penicillins, the most important -lactam inductors of immediate allergic reactions. According to these results, we hypothesize that pyrazinone B 1 b may be recognized by IgE specific to cefaclor or cefprozil (cephalosporins with equal R SP 1 sp ) but to a lesser extent by IgE specific to ampicillin (penicillin containing the same R SP 1 sp ). [Extracted from the article]

Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell–mediated reactions classically occur more than 6 hours after drug administration and include life‐threatening conditions such as toxic epidermal necrolysis, Stevens‐Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA‐B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA‐compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim‐sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future. [ABSTRACT FROM AUTHOR]

GNAI2 variants predict nonsteroidal anti-inflammatory drug hypersensitivity in a genome-wide study Keywords: G proteins; GNAI2; hypersensitivity; Nonsteroidal anti-inflammatory drugs (NSAIDs) EN G proteins GNAI2 hypersensitivity Nonsteroidal anti-inflammatory drugs (NSAIDs) 1250 1253 4 05/20/20 20200501 NES 200501 To the Editor, 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 hypersensitivity 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 results in patients and paired controls from central Spain. Drug hypersensitivity reactions (DHRs) involve the release of cellular mediators through both specific and nonspecific immunological mechanisms.[1] Nonspecific immunological mechanisms are the mainstay of nonsteroidal anti-inflammatory drug (NSAID)-induced DHRs. [Extracted from the article]

The article discusses a study on immediate allergic reactions to proton pump inhibitors, specifically omeprazole. The research found that the Basophil Activation Test (BAT) positivity decreases over time after the reaction, emphasizing the importance of conducting allergology studies close to the reaction. The study followed 18 patients with omeprazole allergy for three years, showing that BAT remains reliable for evaluating immediate reactions to omeprazole, especially in severe cases, but the duration of positivity is influenced by activation levels post-reaction. [Extracted from the article]

Introduction Methods Results Conclusion Basophil activation test (BAT) might be an alternative to nasal allergen challenge (NAC) to identify the allergic etiology in rhinitis patients. Here, we investigate the diagnostic performance of BAT for allergic phenotypes of rhinitis.Rhinitis patients and healthy controls were subjected to NAC with Dermatophagoides pteronyssinus (DP), Alternaria alternata (AA), grass (GP) and olive (OP) pollens. Rhinitis subjects also underwent skin prick test (SPT) with relevant allergens. Patients were classified into allergic rhinitis (AR, positive NAC and SPT), local allergic rhinitis (LAR, positive NAC and negative SPT), dual allergic rhinitis (DAR, defined as AR for ≥1 allergen and LAR for ≥1 allergen), and non‐allergic rhinitis (NAR, negative NAC and SPT) phenotypes. BAT with DP, AA, GP and OP was conducted in study individuals and compared with NAC results.A total of 47 AR, 31 DAR, 26 LAR, 12 NAR and 21 control subjects were recruited. The best positivity cut‐offs of BAT for DP‐, AA‐, GP‐ and OP‐driven allergy (all phenotypes) were a %CD63 cells of 8.650, 14.250, 26.200, and 12.780, respectively (AUC 0.851, 0.701, 0.887, and 0.921, respectively).Sensitivity, specificity, negative and positive predictive values of BAT (all phenotypes) ranged 43.5%(AA)‐83.3%(OP), 88.9%(GP)‐100%(AA), 87%(GP)‐100%(AA), and 61.1%(DP)‐80.0%(pollens), respectively. BAT identified 79%–100% of SPT‐positive allergies (AR and DAR), and 25%–75% of SPT‐negative allergies (LAR and DAR), while ≤10% of NAR/HC subjects tested positive. BAT positivity correlated with rhinitis severity in LAR patients (p = 0.018), and associated with conjunctivitis (p = 0.015) in allergic subjects.BAT can replace NAC for AR confirmation, and limit the number of NAC required for LAR and DAR diagnosis. BAT can demonstrate sIgE in SPT‐negative allergies. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of an algorithm for diagnosing betalactam (BL) allergy. The diagnostic process involves a clinical history, skin tests, in vitro tests, lymphocyte transformation tests, and drug provocation tests. The sensitivity and specificity of these tests vary, with skin tests and in vitro tests showing lower sensitivity but higher specificity. The article also discusses risk stratification, the development of assessment tools, and the use of alternative drugs for allergic patients. It includes a list of various antibiotics categorized by generation, along with recommendations for administration and testing based on structural similarities. The document is authored by a group of researchers and clinicians from Spain and provides references for further exploration. [Extracted from the article]

Background Methods Results Conclusions Delabelling pathways offer confirmatory diagnosis and can prevent unnecessary second‐line therapies or drug desensitization procedures after chemotherapeutic hypersensitivity reactions (CHT‐HSRs). However, these pathways rely on risky in vivo tests. Data on whether in vitro tests could be helpful are scarce. We assessed the role of basophil activation test (BAT) in the diagnosis of HSRs to platin salts (PSs) and taxanes (TXs) in a well‐defined population featuring varied endophenotypes and severities of HSRs.We conducted a 3‐year‐long multicentric, prospective study with 121 suspected‐immediate CHT‐HSR patients. The allergy workup included clinical history (initial reaction based on Type I, cytokine release syndrome, and mixed phenotype's symptoms and if unable to fit in any of these, as “indeterminate”), skin testing (ST), and drug provocation testing (DPT), provided risk assessment was favorable. Final diagnosis classified patients as “hypersensitive,” “non‐hypersensitive,” or “inconclusive.” We performed BAT using CD63 and CD203c as activation markers in patients and controls. Patients underwent DPT regardless of BAT results to prevent bias.ST positivity significantly correlated with skin involvement, Type I phenotype, cancer recurrence, and lifetime exposures before reactions. DPTs were negative in all indeterminate phenotype patients (p = .02) and those considered low‐risk, whereas they were negative in 62% moderate‐risk patients. 55% were confirmed as hypersensitive (mainly Type I reactions, p < .0001), 24% as non‐hypersensitive (mainly TXs and indeterminate phenotypes), and 21% as inconclusive. BAT showed 79% sensitivity in Type I IgE‐mediated reactions to PSs with a high correlation to ST.BAT is a promising tool for delabelling and endotyping CHT‐HSRs, especially Type I reactions to PSs, possibly identifying patients at risk of positive DPT. ST seems useful in confirming CHT‐HSRs, especially PS‐induced reactions, and DPT remains the gold standard, being essential even in moderate‐risk patients. [ABSTRACT FROM AUTHOR]