UNASSIGNED: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations.
UNASSIGNED: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks.
UNASSIGNED: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, \"dyspnea\" and \"headache\" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies.
UNASSIGNED: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters.
UNASSIGNED: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE-mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE-FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues.

Accurate identification of the allergy-eliciting stinging insect(s) is essential to insuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy (VIT). Diagnostic testing using whole venom extracts with skin tests and serological-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in clinical history-positive patients. As a second-level evaluation, serological testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 versus yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from inter-species cross-reactivity [hyaluronidases (Api m 2, Ves v 2, Pol d 2) and dipeptidyl peptidases IV (Api m 5, Ves v 3, Pol d 3)]. Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole venom and molecular venom allergens (highlighted above) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom allergic patient testing with maximally achievable analytical sensitivity (0.1 kUA/L) and confirmed reproducibility (inter-assay CVs<10%). Emerging oligo- and multiplex (fixed panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient\'s clinical history, combined with the proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.

BACKGROUND: In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100 IU/mL at baseline.
METHODS: Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline.
RESULTS: Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: -31.9% (-41.9; -22.6); placebo: -6.3% (-21.3; 14.9)] and week 24 [dupilumab: -48.2% (-56.8; - 39.5); placebo: - 6.3% (-34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes.
CONCLUSIONS: Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04180488.

BACKGROUND: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management.
METHODS: We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients\' profile, and an assessment of OMA efficacy and safety.
RESULTS: We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing.
CONCLUSIONS: One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.

UNASSIGNED: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping.
METHODS: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens.
RESULTS: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients\' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes.
CONCLUSIONS: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

UNASSIGNED: Chronic Rhinosinusitis (CRS) is a common condition causing a significant worldwide burden, affecting 5%-12% of the general population. CRS is classified into type 2 and non-type 2 disease based on endotype dominance. Type 2 inflammation is distinguished by the presence of IL-4, IL-5, and IL-13 cytokines, along with eosinophil and mast cell activation and recruitment. Evidence of type 2 inflammation is ascertained by tissue eosinophil count >10/high-power field (HPF) or serum eosinophil >250 cells/mcL or total immunoglobulin E (IgE) > 100 IU/ml.
UNASSIGNED: To investigate the prevalence and characteristics of type 2 inflammation in patients who presented with nasal polyps and underwent Endoscopic Sinus Surgery (ESS) in Saudi Arabia.
UNASSIGNED: A retrospective cross-sectional Study.
UNASSIGNED: This study was conducted among patients who presented with nasal polyps and underwent ESS at King Saud University Medical City (KSUMC) from 2015 to 2020. Patients with nasal/sinus diseases other than Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) were excluded. Demographic data, olfaction status, and co-morbidities were collected, and radiological images were evaluated. Type 2-CRS was determined by meeting at least one of three predictor criteria (blood eosinophils ≥250 cells/mcL, tissue eosinophils ≥10/HPF, or total IgE levels ≥100 IU/ml). Blood parameters and histopathologic analysis were obtained for each patient.
UNASSIGNED: Of the 381 patients included in the study, the prevalence of type 2-CRS, based on the EPOS2020 criteria, was 99.7% in our population. Among these patients, 47.5% had hyposmia, 38.8% had anosmia, and 13.6% had normal olfaction. The most prevalent co-morbidity was allergic rhinitis, followed by bronchial asthma.
UNASSIGNED: This study aimed to determine the prevalence of type 2 inflammation among patients Diagnosed with CRSwNP and underwent ESS in Saudi Arabia. The results showed a prevalence of 99.7%, indicating that almost all recorded patients with CRSwNP in our population had type 2 inflammation.

Immune tolerance to foods develops in the intestine upon food ingestion and is essential to prevent IgE-mediated food allergy and gut inflammation. In homeostasis, the intestine is a tolerogenic environment that favors the formation of food-specific Foxp3+ regulatory T cells. A tolerogenic intestinal environment depends on colonization by diverse microbiota and exposure to solid foods at a critical period in early life. These early immune responses lead to the induction of antigen-specific Foxp3+ regulatory T cells in draining mesenteric lymph nodes. These peripherally induced regulatory cells circulate and seed the lamina propria of the gut, exerting suppressive function systemically and locally in the intestine. Successful establishment of a tolerogenic intestinal environment in early life sets the stage for oral tolerance to new antigens in adult life.

Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.