IgE-mediated Reactions Research Articles

P-996. Antibiotic Selection for Group B Streptococcus Prophylaxis in Penicillin Allergic Pregnant Patients

Abstract Background Penicillin (PCN) is preferred by American College of Obstetricians and Gynecologists (ACOG) for the prevention of early-onset Group B Streptococcus (GBS infections in newborns, but 10% of patients report a PCN allergy. Clindamycin and vancomycin are second-line for GBS prophylaxis because they are less effective; thus ACOG recommends PCN testing in pregnant patients who report an allergy. Cefazolin has limited cross-reactivity in IgE-mediated PCN reactions and has excellent activity against GBS. This study aims to determine how PCN allergy testing is utilized in GBS positive, PCN allergic pregnant patients and its effect on antibiotic selection. Methods This is a single-institution, IRB approved, retrospective cohort of patients that gave birth with an EHR documented PCN allergy from January 1, 2022-July 30, 2023. Pregnant patients over the age of 18 with a penicillin allergy and received antibiotics with an indication for GBS prophylaxis were included. Patients were excluded if they received antibiotics for indications other than GBS prophylaxis. The primary outcome was the rate of PCN used compared to cefazolin in skin-tested and non-skin-tested pregnant patients with indications for GBS prophylaxis. The secondary outcomes were rate of PCN allergy testing, adverse effects due to the antibiotic, the rate of neonatal early-onset sepsis, and frequency of PCN use compared to other antibiotics. Results Of 4,780 births, 57 patients met inclusion criteria. Of those 57 patients, only 2 patients received PCN allergy testing referrals. Only 1 of the 2 PCN skin-tested patients had a negative result; however, both patients received cefazolin. The 55 patients without skin testing consults received penicillin (3.9%), cefazolin (51%), clindamycin (22%) and vancomycin (27.5%). Of the 25 patients who received clindamycin or vancomycin, all could have received cefazolin based on allergy cross reactivity data. There were no antibiotic-related adverse effects or neonatal early-onset sepsis. Conclusion PCN allergy testing was found to be used very infrequently in this population; providers should be educated about the availability of this service. Additionally, providers should be educated regarding cross-sensitivity with PCN allergy and encouraged to use cefazolin for GBS prophylaxis. Disclosures YoungYoon Ham, PharmD, Gilead: Honoraria

Beyond the “Master” Role in Allergy: Insights into Intestinal Mast Cell Plasticity and Gastrointestinal Diseases

Mast cells (MCs) are essential components of the immune system that enter the circulation as immature bone marrow progenitors and differentiate in peripheral organs under the influence of microenvironment factors. As tissue-resident secretory immune cells, MCs rapidly detect the presence of bacteria and parasites because they harbor many surface receptors, which enable their activation via a multitude of stimuli. MC activation has been traditionally linked to IgE-mediated allergic reactions, but MCs play a pivotal role in different physiological and pathological processes. In gut, MCs are essential for the maintenance of gastrointestinal (GI) barrier function, and their interactions with neurons, immune cells, and epithelial cells have been related to various GI disorders. This review recapitulates intestinal MC roles in diseases with a main focus on inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Emerging therapies targeting MCs and their mediators in clinical practices will also be discussed.

P-1822. Management of Patients with a History of Penicillin Allergy: A Retrospective Observational Study from Saudi Arabia

Abstract Background It has been estimated that 8 to 25% of populations studied globally are labeled penicillin-allergic. However, almost 90% of these patients may not have a true allergy upon work-up, which led prescribers to substitute β-lactams unnecessarily with other broadspectrum antibiotics. Therefore, the aim of this study was to describe how patients with a history of penicillin allergy are treated for infectious diseases, and determine the cost associated with alternative antibiotics.Table I.Baseline characteristics of patients with a documented history of penicillin allergy. Methods A retrospective observational study conducted in a tertiary-care teaching hospital in Riyadh, Saudi Arabia. Approval was obtained from the Institutional Review Board, and electronic health records (EHRs) of patients were included if they were 18 years old and older, labeled to have penicillin allergy, and were admitted in medical wards or treated as outpatients. Results Among the 235 included patients, the type and severity of allergy reactions were not reported in the majority of patients 200 (85%) and were described in only 35 (15%) patients, which 27 (12%) of them had IgE-mediated allergic reactions (angioedema, anaphylaxis, bronchospasm, and urticaria). None of the cases were referred to an immunologist. Most common antibiotic indications included surgical prophylaxis 81 (33%), followed by respiratory 64 (27%) and gastrointestinal infections 40 (17%). For patients with documented penicillin allergy, macrolides were the most used alternative antibiotics followed by clindamycin, cephalosporins, and fluroquinolones in 63 (26%), 56 (24%), 50 (21%), and 30 (12%) patients, respectively. Conclusion This study reveals that mislabeling penicillin allergies in Riyadh's tertiary hospital leads to using less effective antibiotics, increasing adverse reactions, infections, and healthcare costs. It emphasizes improving allergy verification to enhance antibiotic use and reduce expenditures. Disclosures All Authors: No reported disclosures

365. Amoxicillin Direct Oral Challenge in Patients with High-Risk Allergic Reaction

Abstract Background Historically, penicillin skin testing (PST) has been the first step in allergy evaluation, followed by an oral challenge (OC). Recently, there have been studies looking at the safety of direct OC in patients without a prior PST, mostly in patients with a history of a mild reaction, such as distant rash or unknown reactions. There is, however, a paucity of data for OC without a PST for patients who report a high-risk reaction to penicillin. Our hospital protocol allows for OC without PST of patients who have had a severe IgE-mediated reaction, as long as the reaction occurred more than 10 years ago. Methods Patients over the age of 18 admitted with a high-risk penicillin allergy who were tested with a direct OC were included. High-risk reactions include anaphylaxis, angioedema, hives, as well as shortness of breath. Patients that had a PST prior to an OC or did not have a penicillin allergy were excluded. Data collected were age at the time of challenge, reported allergy and historic reaction, presence of other high-risk allergies, onset to symptoms, time since last reaction, and result of OC. If the challenge resulted in a reaction to penicillin and inability to de-label the allergy, data on reaction and use of rescue medications were also collected. Results Of the 288 patients who had received an OC at our institution, 9 were excluded due to prior PST and 2 were excluded due to a non-penicillin allergy. One hundred eight were additionally excluded due to their initial allergic reaction not being high-risk. One hundred sixty-nine patients were included in the analysis. Of the 169 patients with a history of high-risk reactions, 46 patients specifically reported anaphylaxis and 34 patients reported angioedema. One hundred and fifty-nine patients (94.1%) passed the OC and had the allergy de-labeled. Of the 10 patients (5.9%) who reacted during the OC, 3 required diphenhydramine and one required albuterol. The rest did not require the use of rescue medications and were simply observed until the reaction passed. Epinephrine was not used for any patient as a rescue medicine. Conclusion Direct OC without a prior PST for patients who report a high-risk allergic reaction to penicillin drugs is reasonable after 10 years have passed from the initial reaction. Disclosures YoungYoon Ham, PharmD, Gilead: Honoraria

Effective desensitization in an IgE-mediated hypersensitivity reaction to tocilizumab in neuromyelitis optica

Effective desensitization in an IgE-mediated hypersensitivity reaction to tocilizumab in neuromyelitis optica

Early markers of baked milk and egg tolerance in young children with IgE-mediated immediate reactions.

Background. Children with milk and egg allergies have outcomes in which, three-quarters are tolerant to baked forms of the allergenic food. Identifying predictors of tolerance to baked foods for IgE-mediated immediate-type reactions may guide the early introduction of baked allergens to diet and tolerance development. This study explores factors associated with early tolerance to baked foods. Methods. We retrospectively analysed patients with IgE-mediated immediate-type food allergy in infancy who either became tolerant to the baked form before two years or remained reactive after two years. Results. We examined 143 patients solely with IgE-mediated immediate-type egg and/or milk allergies excluding the ones having atopic dermatitis, 76 (42 egg-allergics; 34 milk-allergics) achieved tolerance, and 67 (38 egg-allergics; 29 milk-allergics) were reactive beyond the age of two. Independent markers favoring tolerance to baked forms at two years included the absence of anaphylaxis during the first reaction, applicable to milk and egg allergens. The absence of familial atopy and concomitant egg allergy were also independent predictors for milk-allergic subjects. Receiver operating characteristic analysis determined cut-off values for specific-Immunoglobulin E (sIgE) levels (kU/L) predicting mild phenotype at first admission: egg white-sIgE ≤ 7.39, milk-sIgE ≤ 5.99, and casein-sIgE ≤ 4.99, with AUC values of 0.703, 0.716, and 0.749, respectively. Conclusions. This study identifies key prognostic for tolerance of baked allergen for IgE-mediated immediate-type reactions, providing valuable insights to determine the patients who need more intensive care versus the ones who don't need baked allergen avoidance early in their life from their initial admission at infancy.

Successful Desensitization to Irinotecan in a Patient with Metastatic Esophageal Squamous Cell Carcinoma and a History of Anaphylaxis in Response to Irinotecan-Case Report and Literature Review.

Background:Irinotecan is a topoisomerase I inhibitor used for the treatment of various cancers, such as gastrointestinal, pancreatic, pulmonary, ovarian, and cervical cancers. Among chemotherapy agents, it represents a rare trigger of drug hypersensitivity reactions, with few cases being reported until today. Methods: We present the case of a patient with metastatic esophageal cancer and a history of irinotecan-induced grade IV (WAO classification) anaphylaxis. An IgE-mediated reaction was confirmed in our case, as evidenced by a positive intradermal skin test result, and we carried out a successful desensitization protocol, given irinotecan's indispensability in the treatment regimen. Our case underscores the fact that in such situations where the culprit drug is also the only therapeutic option available for such a patient, implementing a desensitization protocol may represent the only viable approach to ensure safe and successful dosing. Results: A comprehensive review of the literature was also conducted to assess previously reported irinotecan-induced hypersensitivity reactions, the utility of skin tests in identifying sensitisation to irinotecan, and the existing desensitization protocols. We found a total of seventeen cases of hypersensitivity reactions to irinotecan in the literature, out of which four provided the skin test results obtained and six performed desensitization protocols for irinotecan. Conclusions: Our literature review highlights that skin testing and desensitization protocols can provide suitable solutions for managing hypersensitivity reactions to irinotecan.

Approach to a Child with Cow’s Milk Allergy

Cow’s milk allergy is a common problem in childhood that needs frequent visits to a pediatrician. The objective of this review is to provide the general pediatrician with an overview of cow’s milk allergy in children discussing the etiology, patient evaluation, and management. This review provides an approach to a child with cow’s milk allergy based on the best available evidence from electronic literature searches. Cow’s milk allergy may be IgE-mediated, non-IgE-mediated, and mixed. IgE-mediated reactions occur immediately after ingestion of milk. Skin manifestations like erythema, hives, pruritus, angioedema, and flaring of eczematous lesions are common manifestations of IgEmediated food allergy. Non-IgE-mediated cow’s milk allergies are proctocolitis, enterocolitis, enteropathy, and contact dermatitis. Cow’s milk-induced allergic proctocolitis is the common cause of rectal bleeding from 1 day to 6 months of age. The key to the diagnosis of food allergy depends on obtaining a good history and physical examination. Quantitative measurements of serum cow’s milk specific IgE and skin prick test are useful tests. Strict avoidance of the offending food is the mainstay of management. Bangladesh J Child Health 2023; Vol 47 (2) : 59-64

Revealed at last: Structure of the antibody-receptor complex common to all IgE-mediated allergic hypersensitivity reactions.

Immunoglobulin E (IgE) binds with high affinity to its receptor, FcεRI, on mast cells and basophils, and cross-linking of allergen-specific IgE by minute amounts of multivalent allergen stimulates a powerful and immediate allergic reaction. In this issue of Science Signaling, Zhang et al. report the three-dimensional structures of the human and murine receptors, with and without bound IgE-Fc, to reveal some intriguing differences between mouse and human in this critical antibody-receptor interaction.

Heat Treatment of Hazelnut Allergens Monitored by Polyclonal Sera and Epitope Fingerprinting.

Hazelnuts are frequently involved in IgE-mediated reactions and are the main cause of nut allergies in Europe. Most food products are processed before human consumption. Food processing can modify the structure, properties, and function of proteins, and as a result, the IgE-binding capacity of allergens can be affected. In this study, we aimed to investigate epitope changes caused by the roasting of hazelnuts using epitope fingerprinting. Rabbit sera were raised against hazelnut proteins, and their epitopes were characterized. Immunoassays using specific polyclonal antibodies from rabbits targeting the main allergens in hazelnuts revealed marked reductions in the levels of Cor a 1 (PR-10), Cor a 11 (7S globulin), and Cor a 14 (2S albumin). However, rabbit antibodies can recognize different epitopes. Using antibodies that are different and characterized could help establish reliable methods for estimating the effects of treatments on the allergenicity of foods. In this work, we provide the first practical application that could lead to sets of peptide epitopes to compare and standardize immune diagnostics, even for complex protein preparations.

Effect of Small-Molecule Natural Compounds on Pathologic Mast Cell/Basophil Activation in Allergic Diseases.

Pathologic mast cells and basophils, key effector cells in allergic reactions, play pivotal roles in initiating and perpetuating IgE-mediated allergic responses. Conventional therapies for allergies have limitations, prompting exploration into alternative approaches such as small-molecule natural compounds derived from botanical sources. This review synthesizes the existing literature on the effects of these compounds on pathologic mast cells and basophils, highlighting their potential in allergy management, and utilizes the PubMed database for literature acquisition, employing keyword-based searches to identify relevant peer-reviewed sources. Additionally, mechanistic insights were evaluated to contextualize how small-molecule natural compounds can inhibit mast cell/basophil activation, degranulation, and signaling pathways crucial for IgE-mediated allergic reactions. Small-molecule natural compounds exhibit promising anti-allergic effects, yet despite these findings, challenges persist in the development and translation of natural compound-based therapies, including bioavailability and standardization issues. Future research directions include optimizing dosing regimens, exploring synergistic effects with existing therapies, and employing systems pharmacology approaches for a holistic understanding of their mechanisms of action. By harnessing the therapeutic potential of small-molecule natural compounds, effective treatments for allergic diseases may be realized, offering hope for individuals with allergies.

Cellular and Humoral Response After Induction of Protection and After Finishing Hymenoptera Venom Immunotherapy.

Hymenoptera venom allergy (HVA) is an IgE-mediated hypersensitivity reaction caused by Hymenoptera species stings (honeybee, vespid, or ant). The only effective treatment is Hymenoptera venom immunotherapy (VIT). Our study aimed to evaluate whether humoral and cellular biomarkers measured before, during, and after honeybee VIT are associated with the success of VIT, which was assessed by the response to a sting challenge one year after finishing VIT. In this prospective study, blood biomarkers of 25 patients undergoing honeybee VIT at the referral center in Slovenia were evaluated. A controlled honeybee sting challenge confirmed successful VIT in 20 of 25 (80%) patients. Honeybee venom (HBV) recombinant allergen profiles, evaluated before the treatment, were comparable between responders and non-responders. Longitudinal follow-up, up to 1 year after finishing VIT, showed that the immune responses do not differ significantly between patients with successful VIT and treatment failure. Those responses were characterized by decreased sIgE, tIgE, and BST, whereas sIgG4 levels increased. The basophil sensitivity also significantly decreases after VIT in both groups of patients. The analyzed biomarker which correlated considerably with treatment failure was higher basophil sensitivity to allergen stimulation before VIT. Similarly, systemic adverse events (SAEs) during the build-up phase of VIT correlated with treatment failure. Our study demonstrated similar sensitization profiles, and humoral and basophil immune responses to immunotherapy, in two different well-characterized groups of patients, one with successful VIT and the other with treatment failure. Notably, only high basophil sensitivity measured before VIT and SAEs during VIT were significantly associated with VIT failure, and both have the potential to be predictors of VIT failure.

Clinical diagnosis and management of wheat and buckwheat allergy: application and prospects of allergen component diagnostics

Wheat and buckwheat allergies are common food allergies that significantly impact patients' quality of life and health. Wheat allergy encompasses various forms, including wheat food allergy, exercise-induced allergic reactions (WDEIA), baker's occupational asthma/allergy, and contact urticaria. IgE-mediated allergic reactions involve sensitization to stable wheat allergens such as ω-5 gliadin and gluten. Although buckwheat allergy is less common, it is gaining attention in certain regions. Allergen component diagnostic technologies, by detecting specific allergen components [e.g., ω-5 gliadin, gliadins (α, β, γ), and Tri a 14], offer precise allergen source identification, aiding in the optimization of diagnosis and management processes. Oral challenge tests are considered the gold standard for diagnosing wheat allergy, and combining skin prick tests with specific IgE measurements can enhance diagnostic accuracy. While avoidance of allergens remains the primary management strategy, research into immunotherapy is ongoing. Future research should focus on a deeper understanding of the structural and immunological characteristics of wheat and buckwheat allergens to develop more accurate diagnostic tools and treatment methods, thereby improving allergy management and patient quality of life. This article provides a detailed interpretation of the Molecular Allergology User's Guide 2.0 (MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and recent research advances on wheat and buckwheat allergies, highlighting the crucial role of allergen component diagnostics in optimizing food allergy diagnosis and treatment processes, supporting clinicians in accurately identifying common allergens and their cross-reactivity, and formulating more personalized treatment plans for patients.

Comparing Two Peanut Desensitization Protocols in Preschool Children: A Real-World Clinical Practice.

Peanut allergy is the main food allergy in childhood and poses significant health concerns. This study aimed to critically evaluate the effectiveness and safety of oral immune therapy (OIT) using crushed peanuts versus peanut puffs. Children with an allergist diagnosed peanut allergy based on a history of an IgE-mediated reaction and a positive skin prick test for peanuts were recruited at the Montreal Children's Hospital and the Children's Clinic located in Montreal. Based on age and personal preference, initial doses of peanut were given in either puff (Bamba) or crushed peanut form. Patients continued the same dose for 2-5 weeks at home, filled out a symptom diary, and returned to the clinic for up-dosing until maintenance was reached (2 teaspoons of peanut butter). A continuation ratio regression model was used to evaluate the effect of the allergen type on the severity of anaphylactic and allergic reactions (ARs) during OIT while adjusting for potential confounders. Between October 2020 and June 2023, 191 children (59.6% male; median age 1.95 years) were recruited. Most patients (75.1%) had eczema, and 12.7% had asthma. Oral desensitization was performed using one of two strategies according to the allergist: crushed peanut (n = 60 [31.4%]) and peanut puff (n = 131 [68.6%]). Of the participants, the consumption of puff lowered reaction severity by a factor of 3.94 (95% CI, 1.6-9.6), in comparison to crushed peanuts. Older age markedly elevates the adjusted odds of reacting to a particular severity level as compared to a lower level by 1.20 (95% CI, 1-1.4). Modified peanut desensitization using peanut puffs has shown potential in reducing the severity of ARs in younger children. Older children may experience a higher risk of severe reactions, indicating the need for age-specific approaches to desensitization protocols.

GA2LEN ANACARE consensus statement: Potential of omalizumab in food allergy management.

Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.

Intensive Care for Anaphylaxis in Children: Current Trends

Anaphylaxis is an acute allergic reaction with rapid clinical development and risk of death. This article provides an analysis of literary sources devoted to intensive care of anaphylaxis in childhood. It was revealed that the prevalence of anaphylaxis is increasing, in children and adolescents as well. The main triggers of anaphylaxis in pediatric practice include food products, insect bites and drugs. Anaphylaxis is an IgE-mediated hypersensitivity reaction of type 1, characterized by the release of chemical mediators that lead to smooth muscle contraction, increased permeability and vasodilation and vagal activation. Clinically, anaphylaxis is manifested by allergic skin rash, angioedema, obstruction of the upper respiratory tract (URT), broncho-obstructive syndrome (BOS), arterial hypotension, tachycardia. Intensive care for anaphylaxis in children begins with stabilization of the condition: stopping the entry of a possible allergen into the body, hospitalization in the anesthesiology and intensive care unit, restoring patency of the URT, conducting oxygen therapy, monitoring vital functions. The first-line drug for the treatment of anaphylaxis in children is adrenaline at a dose of 0.01 mg/kg, which stops all the main pathophysiological links of anaphylaxis. Adrenaline autoinjectors are not used in the Russian Federation. Second-line drugs for intensive care for anaphylaxis in children include glucocorticosteroids (GCS), antihistamines, bronchodilators and infusion therapy. The effectiveness of GCS in anaphylaxis in children has not been proven, antihistamines can relieve skin manifestations of an allergic reaction, but do not affect vital disorders. Bronchodilators reduce BOS and are an additional treatment, while infusion therapy eliminates hypovolemia. Knowledge and timely implementation of modern care algorithms for anaphylaxis in children and adolescents will improve the quality of emergency care and reduce the risk of fatal outcomes in this pathology.

Short-term influence of Immufen™ on mild allergic rhinitis: a randomized, double-blind, placebo-controlled study.

Allergic rhinitis (AR) is an IgE-mediated reaction to inhaled allergens, and is a prominent health concern affecting approximately 400 million people worldwide. A comprehensive understanding of AR's pathophysiology is imperative for developing novel therapies, especially considering its frequent co-morbidity with asthma and conjunctivitis. The escalating prevalence of AR is correlated with increased urbanization and environmental pollutants, recognized as prominent contributing factors. Dysregulation in immune networks, Th1/Th2 cytokine imbalance, activation of mast cells and eosinophils are implicated in AR progression. Classic AR symptoms include nasal congestion, nasal itching, rhinorrhea, and sneezing which significantly impact the quality of life, social interactions, and workplace productivity. This randomized, double-blind, placebo-controlled, three-arm, three-sequence study was aimed to assess the efficacy of supplementation of a co-delivery form of turmeric extract with ashwagandha extract (CQAB) in comparison with a bioavailable curcumin (CGM) and placebo in alleviating AR symptoms and enhancing the quality of life in individuals with mild AR. Participants received either placebo, CGM, or CQAB twice/day for 28 days, and subjective measures were recorded at the baseline and at the end of study. CQAB supplementation demonstrated a significant (P < 0.05) improvement in Total Nasal Symptom Score (TNSS) compared to placebo and CGM. Furthermore, CQAB administration resulted in enhanced sleep quality (P < 0.05) as evaluated by the BIS questionnaire, heightened energy levels, and decreased fatigue and overall mood disturbance (POMS-SF) compared to both placebo and CGM. The results suggests that CQAB has the potential to be used as a dietary supplement in alleviating AR discomforts. https://ctri.nic.in/Clinicaltrials/login.php; Identifier CTRI/2021/01/030355.

Genetic variability of the major birch pollen allergen Bet v 1 and characterization of B- and T-cell epitopes

The hanging birch pollen collected in the period April – May 2020, 2021 in the territory of six regions of the Republic of Belarus was studied. Recombinant plasmid DNA was obtained. A nucleotide sequence of cloned fragments was determined. The results on the spectrum of isoforms of the Bet v 1 protein were analyzed. The obtained sequences corresponded to one degree or another to 11 genetic variants of the studied allergen. There were 7 isoforms of Bet v 1 defined within one tree. The predominant isoform of the birch pollen allergen Bet v 1 in the territory of the Republic of Belarus was Bet v 1.0101 (Bet v 1a, X15877.1). The identified variants were analyzed for their potential allergenicity by screening amino acids that according to the literature data were identified as affecting IgE-binding. The analysis of amino acid residues included in the IgE-binding conformational epitopes revealed amino acid substitutions exhibiting the multidirectional (high or low) IgE-binding activity in positions 31, 58, 113, 114, 126. The structure of dominant epitopes recognized by the T-cell receptor was studied. It was found that the C-terminal immunodominant T-cell epitope Bet v 1143–157 is highly conserved among various isoforms of the allergen in contrast to the epitope Bet v 178–93 located in the central region. The revealed amino acid substitutions of the studied sites can affect the activation of T-cells, cross-reactivity and significantly increase the variability of the expected IgE-mediated reaction.

The decrease in peripheral blood basophils in a mouse model of IgE-induced inflammation involves their migration to lymph nodes

During the active phase of urticaria, a decrease in peripheral blood basophils, known as basopenia, is observed. We previously reported that basopenia occurs as a result of basophils migrating to the skin in a contact dermatitis model where a Th2 response is induced with oxazolone. Although there is currently no established model for urticaria, given that urticaria is an IgE-mediated immediate-type allergic reaction, we aimed to determine whether an IgE-mediated model could reproduce the decrease in basophils in peripheral blood observed during the active phase of urticaria. Mice were pretreated with 2,4,6-trinitrophenylhaptene (TNP)-specific IgE and basophil dynamics were examined following stimulation with TNP-ovalbumin. Mast cell-deficient WBB6F1-KitW/KitW-v mice were used to investigate the role of mast cells in this IgE-mediated model. Following stimulation, we observed immediate ear swelling and basopenia after 0.5 hours. However, the number of basophils observed in the skin lesions was low, while a higher number of basophils were observed in the antigen-draining lymph nodes (LN). In mast cell-deficient mice, no increase in basophils in the LN was observed, reflecting reduced antigen influx into the LN, but basophils remained in the skin. In the IgE-mediated mouse model, basopenia was observed, which coincided with the induction of inflammation in the skin. The migration of basophils to the LN in this model suggests that the systemic immune system, including the LN, should be considered when exploring the pathogenesis of urticaria in humans.

Basophil activation test is a complementary tool in the diagnosis of immediate reactions to platinum salts and taxanes.

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 invivo tests. Data on whether invitro 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.