Cassava oral immunotherapy in cassava-latex allergy: A pilot study.

Predicting outcomes of hazelnut oral food challenge: Pediatric cohort analysis.

Real-World Variation in Post-Dose Supervision and Activity Restriction During Maintenance Cow's Milk Oral Immunotherapy.

Objective Evaluate long-term effectiveness, safety and tolerability of OM-89 (Uro-Vaxom®), an oral immunostimulant derived from bacterial lysates of Escherichia coli, in the prophylactic management of recurrent urinary tract infections (rUTIs) in women in a real-world outpatient gynecology setting. Methods Retrospective, multicenter observational study based on data from women with a diagnosis of rUTI who received a single 90-day cycle of OM-89 therapy. Data were collected from medical records at the Mexican Institute for Infectious Diseases in Obstetrics and Gynecology (IMIGO) clinic in Monterrey, Mexico, between January 2023 and March 2024.. Primary outcomes included time to UTI recurrence, number of UTI episodes post-treatment, and use of antibiotics to treat a UTI. Secondary outcomes included recurrence-free interval and incidence of adverse events. Results A total of 208 women with recurrent UTIs were included. 72.1% received a single OM-89 90-day cycle, while 27.9% underwent two or more 90-day cycles. The mean recurrence-free interval after one OM-89 cycle was 5.3 ± 2.6 years, and 4.6 ± 2.5 years for those with OM-89 multiple cycles. Post-treatment bacterial cultures revealed a significant reduction in bacterial resistance 72.4% of urine samples and 37.0% of vaginal samples (p < 0.001). Conclusion A single 90-day course of OM-89 was associated with a long term reduction in UTI recurrences and antibiotic use in women with rUTIs. These findings support its use as a safe and effective non-antibiotic preventive strategy in clinical practice. Keywords: Recurrent urinary tract infections, OM-89, Uro-Vaxom®, oral immunotherapy, antibiotic stewardship, women's health, E. coli, resistance.

Inhaled salbutamol versus placebo for the treatment of acute IgE-mediated abdominal pain from allergic food reactions (INSPIRE trial): a double-blind randomized trial.

Cashew is a widespread food allergen with a high rate of severe, and near-fatal reactions. Understanding cashew reaction thresholds and its predictors might improve patients' management and precautionary allergen labeling. A prospective cohort study with post hoc analysis of cashew oral food challenges (OFCs) performed at Shamir (Assaf-Harofeh) Medical Center between July-2014 and May-2023. OFCs were performed according to either a diagnostic protocol in patients with suspected cashew allergy or an oral immunotherapy (OIT) protocol, intended to identify individual single highest tolerated dose (SHTD) at the beginning of OIT. No observed adverse effect levels and lowest observed adverse effect levels (NOAEL and LOAEL, respectively) of each OFC were identified. OFCs with extended dosing intervals were performed to determine individual validated SHTD (safe dose). Overall, 293 positive cashew OFCs (155 diagnostic-OFCs and 138 OIT-OFCs) were analyzed. The ED01 and ED05 for all patients were 0.2 mg (range 0.1-4.1) and 0.9 mg (range 0.2-14.8) for discrete, and 0.2 mg (range 0.1-11.7) and 1.2 mg (range 0.3-47.1) for cumulative doses, respectively. Pistachio co-allergy (p < 0.0001), higher sIgE to cashew (p = 0.004), Ana-o-3 (p < 0.001) and pistachio (p = 0.02), and an OIT-OFC protocol (p < 0.001) were associated with lower cashew thresholds. Cashew safe doses for 90% and 75% of the population were only 0.1 and 1 mg protein, respectively compared to 1 and 7.5-10 mg protein for sesame, walnut and peanut. The population cashew ED05 is within the range of other nuts and seeds, but safe doses are lower. Pistachio co-allergy and higher cashew and pistachio sensitization are risk factors for low reaction thresholds.

Allergic diseases continue to increase globally, and accumulating evidence implicates early-life microbial exposures as central determinants of immune tolerance. This review synthesizes advances from 2024 to 2026 regarding probiotic-mediated immune modulation and their translational implications in allergy prevention and therapy. Recent studies confirm strain-specific expansion of Foxp3+ regulatory T cells, suppression of Th2 polarization, reinforcement of epithelial barrier integrity, and durable epigenetic stabilization mediated by short-chain fatty acids such as butyrate. Clinical trials demonstrate benefit in perinatal prevention of atopic dermatitis, modulation of allergic rhinitis symptoms, early-life asthma risk reduction, and probiotic-adjuvanted oral immunotherapy. Probiotics are evolving from adjunctive supplements to biologically active immune modulators with disease-modifying potential. Integration with allergen immunotherapy and precision microbiome profiling may redefine preventive and therapeutic strategies in allergic disease.

Background and objectives: Food allergy, particularly peanut allergy, is a significant and growing health concern, especially in high-income countries. Affecting 2% of children and 1% of adults, peanut allergy is a chronic condition that severely impacts quality of life. The standard treatment remains allergen avoidance, though oral immunotherapy (OIT) has emerged as a potential strategy for desensitization. This systematic review and meta-analysis aims to evaluate the efficacy and safety of peanut oral immunotherapy (POIT) based on randomized controlled trials (RCTs). Methods: A systematic review and meta-analyses were conducted following PRISMA guidelines. Eligible studies included double-blind RCTs evaluating POIT versus placebo or avoidance. Databases such as PubMed, Google Scholar, Cochrane-Controlled Register of Trials, and ClinicalTrials.gov were searched. Risk of bias was assessed using the Cochrane Risk of Bias tool (ROB2), and statistical analysis was performed using the RevMan software. Results: A total of 20 studies with 2161 participants (median age: 8.6 years) were included. POIT demonstrated a significant increase in desensitization rates (RR = 7.25, 95% CI: 2.66–19.79, P = 0.0001). However, POIT was also associated with increased risks of anaphylaxis (RR = 2.27, 95% CI: 1.48–3.47, P = 0.0002) and epinephrine use (RR = 2.05, 95% CI: 1.35–3.12, P = 0.0008). Adverse effects such as gastrointestinal symptoms, respiratory events, and skin abnormalities were more frequent in the POIT group, leading to a higher treatment discontinuation rate (RR = 2.50, 95% CI: 1.20–5.21, P = 0.01). Conclusion: POIT is effective in inducing desensitization in peanut-allergic individuals but carries significant risks, including an increased likelihood of anaphylaxis and adverse events. These findings reinforce previous meta-analyses and highlight the need for individualized risk-benefit assessments in clinical practice. Further research is required to optimize treatment protocols and improve patient safety.

Immune checkpoint blockade and therapeutic cancer vaccines have transformed cancer treatment, yet their clinical application in colorectal cancer remains constrained by the lack of efficient oral delivery strategies for biomacromolecules such as antibodies and protein antigens. Here, we report a smart oral immunotherapy strategy that enables the codelivery of programmed death-ligand 1 antibody (anti-PD-L1) and ovalbumin (OVA) antigen for localized colorectal cancer treatment through an arginine-based polymeric nanoplatform. A biosafe cationic arginine-derived polymer (2A6S) was rationally engineered to electrostatically load both antibody and antigen cargos, while an enteric polymer coating (EudragitL100) protected the nanocomplexes from gastric degradation and ensured intestinal release. This dual-protective oral platform (EAPO NPs) achieved efficient colon lesion delivery and significantly enhanced local antitumor immune activation in an orthotopic MC38-OVA colorectal tumor model. Encouragingly, oral administration of EAPO NPs induced 53.34% tumor inhibition using only twice the antibody/antigen dosage compared with systemic injection, while substantially reducing potential systemic immunotoxicity. By integrating immune checkpoint blockade with antigen-specific immune priming through a single oral nanoplatform, this work establishes a simple, safe, and effective strategy for localized intestinal immunotherapy, which could be applicable to colorectal cancer and other colon-associated diseases.

Background/Objectives: Legume allergy is increasingly recognized as plant-based diets expand and legume proteins are widely used in processed foods. We aimed to characterize the clinical features, sensitization profiles, and management outcomes of IgE-mediated legume allergy in Italian children. Methods: This retrospective single-center study (January 2022–January 2024) included children (<18 years) allergic to ≥1 index legume (pea, lentil, chickpea, common bean, or soy). Diagnosis required a compatible clinical history and evidence of IgE sensitization. Clinical and allergy characteristics were analyzed. Results: Fifty-five children (63.6% male) were included; all had atopic comorbidities, and 96.4% had additional food allergies. Median age at first reaction was 18 months; anaphylaxis occurred at onset in 12.7%, most frequently triggered by pea. Pea (70.9%) and lentil (69.1%) were the most prevalent allergies, with pea causing 50% of index-legume anaphylaxis. Multi-legume allergy predominated (74.5%), with frequent co-allergy among pea, lentil, and chickpea (56–86%). Soy allergy was less frequent and mainly associated with Gly m 4 sensitization. Single-legume allergy (25.5%) was associated with later onset (54 vs. 15 months; p = 0.013) and liver transplantation (21% vs. 2%; p = 0.047). Peanut co-allergy occurred in 25.5%. Among 34 oral food challenges (OFCs), 23.5% were positive, including one case of pea-induced anaphylaxis. Of 16 oral immunotherapy (OIT) protocols initiated, 31.3% reached the full target maintenance dose, 37.5% remained on a lower, partial maintenance dose, and 31.3% were discontinued due to oral allergy syndrome (OAS). Conclusions: Pediatric legume allergy is characterized by early onset, frequent multi-legume involvement, and common co-allergies. In this cohort, pea allergy was associated with the highest proportion of severe reactions. Species-specific differences in severity, patterns of multi-legume involvement, and OIT outcomes should be interpreted cautiously given the limited sample size, while highlighting the need for tailored management and improved risk assessment across legume species.

Pumpkin seed, a member of the Cucurbitaceae family, is increasingly consumed because of its high protein content and perceived health benefits. Along with its growing use, cases of pumpkin seed allergy are being reported. However, data on pumpkin seed allergy and oral immunotherapy (OIT) remain scarce. We conducted a retrospective chart review at a tertiary pediatric center (Sainte-Justine University Hospital Center, Montreal, Canada) including all patients who initiated or completed pumpkin seed OIT since 2019. OIT protocols were individualized, with dose increases typically performed every four weeks. Target maintenance doses were at least 300mg of pumpkin seed protein. Eleven patients (median age at OIT initiation: 6.5years; range 1-12) underwent pumpkin seed OIT. Ten patients (91%) reached maintenance dosing within a median of 9.5months (range 6-22) while one patient discontinued OIT due to persistent abdominal pain. No anaphylactic reactions occurred at home during treatment. Two anaphylactic reactions requiring epinephrine occurred during in-clinic up-dosing visits in a single patient, despite this, the patient ultimately achieved maintenance. Gastrointestinal and oral symptoms were the most frequent adverse events and were generally managed with temporary premedication. Most patients (91%) underwent concomitant multi-food OIT. Patients with significant adverse reactions had high ratios of pumpkin-specific IgE to total IgE. Pumpkin seed OIT appears feasible in a highly atopic pediatric population, with a safety profile comparable to that reported for OIT to other food allergens. Given the increasing dietary exposure to pumpkin seeds, larger prospective studies are needed to better define risk factors and long-term outcomes.

Safety and efficacy of three office-based egg oral immunotherapy protocols.

This review summarizes current evidence on emerging biologics and their evolving role in IgE-mediated food allergy management. The goal is to assess the pros and cons of currently available and under evaluation biologicals. Anti-IgE therapies remain central to biologic-based approaches. Omalizumab improves desensitization rates as monotherapy or when combined with oral immunotherapy (OIT), whose enhances safety and accelerates desensitization efficacy. Next-generation anti-IgE antibodies, including UB-221, show increased potency and promising early results. Less encouraging are data on Dupilumab, targeting IL-4/IL1-3 receptor, in IgE-mediated food allergy. Biologics targeting epithelial alarmins, such as anti-IL-33 (etokimab) and anti-TSLP (tezepelumab), demonstrate encouraging preliminary immunologic and clinical effects, with early success noted in peanut allergy trials. Further research focus is devoted to small molecules and vaccines. Biologics offer a meaningful advance in food allergy treatment by targeting key immune pathways with an agnostic approach, therefore, independent on the specific antigen-specificity. This may offer the benefit of targeting multiple food allergies and also, eventually, further co-morbidities. There is broad evidence for an excellent safety profile for omalizumab. Studies are ongoing on other biologicals to explore the efficacy alongside the safety. A new era is also opened by the introduction of biosimilar on the market, by dramatically amortizing the economic burden. With the availability of multiple therapeutic options, the challenge for clinicians is to provide a personalized approach, shaped on the specific patient's need.

Early oral immunotherapy for food allergy (<3 years of age; eOIT) shows promise for inducing sustained unresponsiveness. However, concerns about its feasibility remain. Parental experiences with eOIT have not yet been studied, but understanding these is crucial for improving its clinical implications. Assessing the feasibility of eOIT from a parental perspective. This sequential explanatory mixed-methods study enrolled parents of children from the ORKA study, a prospective intervention study on eOIT for various allergens. Parents completed a baseline anxiety questionnaire, monthly feasibility questionnaires, and daily adherence diaries. After treatment, focus groups were conducted and analyzed using interpretative phenomenological analysis. Parents of 124 children with 189 treated food allergies were included. They reported little anxiety (mean STAI score 32.6 on a scale of 20-80) and high confidence in managing eOIT. Overall, feasibility was assessed positively (mean feasibility score 16.1-23.6 on a scale of 12-60). Adherence was between 96.7% (dose escalation) and 94.7% (maintenance dosing). The participant dropout rate was 9.7%. Focus groups with 10 participants revealed 5 themes: driven by hope, the hidden burden, navigating obstacles, guiding hands, and gratitude in the journey. Parents were motivated by the hope of tolerance development and desire to actively manage the allergy. However, eOIT was emotionally burdensome, especially during initiation and in maintaining adherence. Practical challenges included dose administration. Professional support and expectation management were perceived as essential. Regardless of clinical outcomes, parents viewed the effort as worthwhile. eOIT is feasible from a parental perspective, though emotionally and practically demanding. A family-centered approach with adequate education, practical guidance, and psychosocial support is recommended.

Food allergy immunotherapy strategies including oral, epicutaneous, and sublingual remain some of the most effective therapeutic options for food allergic patients and are currently the only therapeutic options that are expected to have the potential for long-lasting therapeutic benefits after therapy has ended. Recent studies have identified novel ways of implementing food allergy immunotherapy, including the use of real-world foods for oral immunotherapy and sublingual immunotherapy. Other studies have uncovered key mechanisms for how these therapies induce desensitization to food allergens and sustained unresponsiveness. Notably, many of these mechanisms have the potential for monitoring or predicting therapeutic response. The landscape of food allergy immunotherapy is changing to adapt to the shifting food allergy therapeutic landscape. Many studies are now shifting away from commercial or pharmaceutical products in order to increase accessibility with real world food options.

Cashew allergy presents a significant challenge for oral immunotherapy (OIT), as current treatment approaches often rely on unmodified allergens that carry a high risk of triggering severe immune responses. To address this challenge, this study explores a novel strategy by conjugating resveratrol to cashew allergens using a free-radical grafting method. The conjugation process, initiated by ascorbic acid and hydrogen peroxide, led to covalent bonding confirmed by reductions in free amino and thiol groups and a notable increase in β-turn content from 39.1% to 49.0%, indicating irreversible structural modification. Immunoblotting demonstrated reduced binding to anti-cashew IgG and human sIgE, further confirming structural modification and suggesting diminished allergenic potential, respectively. Cytotoxicity tests using Caco-2 cells confirmed high biocompatibility up to 1000μg/mL, while resveratrol conjugation significantly suppressed TNF-α-induced IL-8 secretion, highlighting the anti-inflammatory properties of the conjugates. These findings support the potential of resveratrol-conjugated cashew allergens as safer, multifunctional candidates for next-generation OIT interventions.

Correlation and Agreement Between Parent-Report and Self-Report Food Allergy Quality of Life Questionnaires After Oral Immunotherapy.

Nutritional, Growth, and Microbiome Implications of Oral Immunotherapy: Unintended Consequences and Clinical Considerations.

Early-life peanut oral immunotherapy associated with long-term ingestion and immunologic changes.

Oral immunotherapy (OIT) can be effective and relatively safe for the treatment of food allergies, especially when started early in life. Grocery store foods used in OIT protocols are often heterogeneous in allergen potency and display product-to-product, lot-to-lot, and unit-to-unit variations, due to raw material variability and processing. This variability complicates dosing and poses a potential risk of anaphylaxis and/or subtherapeutic efficacy for patients. To improve practice, a 'gradient of standardization' framework is proposed, comprising four product categories: products assumed to contain the allergens of interest, products known to contain the allergens but in unknown amounts, partially quantified products, and fully standardized preparations. Based on verified allergen content rather than protein amount, this classification would help clinicians weigh safety and efficacy against feasibility and move toward greater conformity and standardization, supporting evidence-based dosing and probably improving patient outcomes. Ideally, foods as medicines for OIT should be well-described, minimally processed, and, preferably, with defined allergen content. Precise dosing, consistent procedures, neutral vehicles, and validated allergen quantification tools could potentially ensure reproducibility, reduce risk, strengthen clinical effectiveness, and facilitate meaningful comparisons across clinical trials and research studies. We suggest that standardized "pharmaceutical grade" products, while not always a practical option, should be preferred when available.