Frontiers in allergy最新文献

Background & aims: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder in which IgG4 involvement is unclear. We aimed to evaluate immunoglobulin G4 (IgG4) in eosinophilic esophagitis (EoE) and investigate the correlation among IgG4-positive plasma cells in esophageal tissue, total serum immunoglobulin E (IgE), specific IgE, and specific IgG4 (sIgG4) levels to six foods (milk, egg, wheat, soy, peanut, and seafood).

Methods: A retrospective observational study with prospective patient inclusion was conducted from 2017 to 2024 in a real-world setting. Clinical, endoscopic, therapeutic, and outcome characteristics of the patients were collected. Positive staining was defined as >10 IgG4-positive plasma cells per HPF. Peripheral blood analyses included measurements of total IgE, specific IgE, and sIgG4.

Results: Seventy-eight patients were included. Patients with positive histological staining exhibited a significantly higher proportion of endoscopic edema (16.1% vs. 2.1%) (p = 0.045; RR = 8.8, 95% CI:1-79.8) and a greater need for second-line treatment (64.5% vs. 41.3%) (p = 0.04; RR = 2.5, 95% CI:1-6.6). Patients with positive IgG4 histological staining exhibited significantly higher median concentrations of serum sIgG4 to milk casein (50.1 mg_A/L vs. 11.2 mg_A/L; p = 0.005; r = 0.31) and egg (63.4 mg_A/L vs. 20.1 mg_A/L; p = 0.011; r = 0.28) than those with negative stain. Patients who did not show histological response to first-line treatment had significantly higher concentrations of sIgG4 to casein (31.8 mg_A/L vs. 18.6 mg_A/L, p = 0.03; r = 0.26) and egg (45.46 mg_A/L vs. 19.2 mg_A/L, p = 0.03; r = 0.27).

Conclusion: Serum sIgG4 levels to casein and egg were associated with infiltration of IgG4-positive plasma cells in esophageal tissue and a worse disease prognosis.

Introduction: Food allergy protocols are highly variable. While it allows the exploration of multiple scientific questions, it limits the possibility to make general assumptions and point out specific features of allergy to different food allergens. Considering this, our research group has developed a standardized food allergy protocol that has allowed us to study egg, milk and shrimp allergy.

Methodology: In this study, we used the same protocol to develop a model of peanut allergy. BALB/c and C57BL/6 mice were sensitized with a subcutaneous injection of 40mg of peanut protein extract (PPE) adsorbed in 3mg of aluminum hydroxide (Al(OH)₃) on days 0 and 14. From day 21 to 35, as an oral challenge, sensitized and control mice received a whole peanut extract (WPE) as the only source of drinking solution, while naïve groups received water.

Results: After oral challenge, BALB/c and C57BL/6 sensitized mice had higher levels of total and specific IgE in the serum, as well as specific IgG1, than control groups. BALB/c, but not C57BL/6, mice presented higher levels of anti-PPE secretory IgA (SIgA), and lower reactivity to fecal bacteria than control group. Sensitized mice from both strains presented positive cutaneous anaphylaxis reaction. Systemic anaphylaxis was more prominent in C57BL/6 mice, while increase in gastrointestinal transit time was more prominent in BALB/c mice. Lastly, jejunum of BALB/c and C57BL/6 sensitized mice presented higher eosinophil, intraepithelial lymphocyte, and goblet cell count, as well as smaller villi length, than control groups.

Conclusion: Our standardized food allergy protocol enabled the development of a peanut allergy model in two different mouse strains, which not only allows the study of peanut allergy itself, but also its comparison to other allergies triggered by food proteins.

Background: Allergen Immunotherapy (AIT) is largely considered to be the only therapy that can provide relief from allergic rhinitis (AR).Although its effectiveness has been confirmed by the results of a large number of practical studies such as randomized controlled trials, it may in some cases have a poor or no response to treatment due to the development of resistance under the influence of certain risk factors. The purpose of this Meta-analysis was to examine the risk factors for AR resistance to AIT treatment.

Methods: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2025. Study quality was assessed using the NOS scale, AHRQ criteria, and the GRADE framework. Statistical analyses, performed with R 4.5.0 and Stata 14, employed fixed-or random-effects models to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was explored via sensitivity analyses, and publication bias was evaluated using funnel plots with Begg and Egger tests.

Results: A total of 12 studies involving 2,552 patients were included in this Meta-analysis. The results suggest that the following factors may be associated with AR resistance to treatment with AIT. Gender: male (OR = 1.53, 95% CI: 1.08-2.18); Specific diagnostic antibody aspects: s-IgE/t-IgE ratio (OR = 1.09, 95% CI: 1.02-1.16), sIgE, sIgG4; For cytokines: IL-10, IL-35, TGF-beta, IFN-gamma; On blood parameters: Eosinophil; Immune Cell Aspects:TH2/CD4, TFH2/CD4, CD23 + BNSM, CD23 + BSM, TFR/CD4, TFR/TFH2; Clinical/personal characteristics: demographics, disease severity, allergen type, treatment details, treatment adherence, symptom control, lung function, airway inflammation, inflammatory markers, immunologic markers, imaging markers, environmental and behavioral factors. With respect to the heterogeneity analysis, the heterogeneity of the other analyses was relatively low, except for age and t-IgE levels, where there was significant heterogeneity.

Conclusion: The risk of developing resistance to AIT treatment for AR is closely associated with patient factors including gender, antibodies, cytokines, hematological parameters, clinical/personal characteristics, immune cells, and other indicators.

Systematic review registration: PROSPERO CRD420251154551.

Purpose: Skin prick test (SPT) and the level of serum-specific IgE (sIgE) antibodies to shrimp have low specificity in the diagnosis of shrimp allergy. Measurement of sIgE to tropomyosin is available as a test, but the accuracy remains controversial. This study aims to evaluate the diagnostic accuracy of sIgE measurement to tropomyosin in the diagnosis of shrimp allergy and compare the diagnostic performance to SPT and sIgE to shrimp.

Methods: Patients with a history of immediate reaction to shrimp allergy were recruited. All participants underwent SPT with commercial shrimp extract. Measurements of sIgE to shrimp and tropomyosin were carried out. An oral food challenge (OFC) with shrimp was performed to confirm the diagnosis.

Results: Fifty symptomatic patients (mean age 27.3 years) with suspected shrimp allergy were evaluated. OFC confirmed allergy in 13 (26%) patients. Diagnostic modalities offered distinct advantages and limitations. Tropomyosin sIgE (rPen a 1) yielded superior specificity (91.9%) at the cost of sensitivity (23.1%), while extract-based tests (SPT and shrimp sIgE) provided better sensitivity (46.2%-61.5%) but lacked specificity (43.2%-51.4%). Implementing a two-step algorithm-combining SPT with tropomyosin sIgE-successfully optimized specificity to 94.6%. Nevertheless, given the suboptimal predictive values across all methods (PPV 25%-50%; NPV 73%-77%), these tools alone cannot safely guide management, and OFC remains essential.

Conclusion: Measurements of sIgE to tropomyosin provided higher specificity and increased diagnostic efficiency than SPT and measurement of sIgE to shrimp for the diagnosis of shrimp allergy.

Olfactory perception plays a fundamental role in nutrition, emotional development, and social behavior, yet olfactory disorders (OD) in children remain largely underrecognized and understudied. This mini review summarizes current evidence and proposes a structured clinical approach for the evaluation and management of pediatric OD. Etiologies are diverse, encompassing congenital syndromes such as Kallmann and CHARGE, post-infectious and post-traumatic forms, inflammatory airway diseases, and structural or iatrogenic causes. Accurate diagnosis begins with a detailed medical history and comprehensive ENT examination, complemented by psychophysical olfactory testing adapted for pediatric populations. Although several validated tools exist-such as the Sniffin' Sticks, U-Sniff, Pediatric Smell Wheel, and pBOT-6-standardized age-specific protocols and normative data remain limited. Imaging techniques, particularly MRI, provide valuable insights into congenital and acquired abnormalities of the olfactory bulbs and tracts, while CT is reserved for sinonasal or bony pathology. Multidisciplinary collaboration among pediatricians, neurologists, endocrinologists, geneticists, and otolaryngologists is essential to achieve etiological precision. Management strategies depend on the underlying cause and include medical or surgical treatment for reversible conditions, intranasal corticosteroids for inflammatory diseases, and olfactory training for post-infectious or congenital forms. Regular follow-up with objective testing and family education supports recovery and long-term adaptation. Despite the scarcity of pediatric-specific evidence, this review highlights the need for awareness, early diagnosis, and individualized management of OD in children, proposing a practical diagnostic and therapeutic framework to guide clinical decision-making in everyday ENT practice. A structured search strategy was applied to summarize the currently available evidence and highlight practical implications for clinical care.

Introduction: Hereditary α-tryptasemia (HαT), defined by increased TPSAB1 copy number and elevated basal serum tryptase, is associated with mast cell (MC)-mediated symptoms. However, its role in gastrointestinal disease remains unclear. Because intestinal MCs express the non-IgE-dependent activation receptor MRGPRX2, we investigated whether MRGPRX2 expression and MC phenotypes are altered in individuals with HαT in the context of inflammatory bowel disease (IBD).

Methods: We genotyped 854 biobanked IBD samples to identify individuals with HαT. Spatial transcriptomic analysis was performed on descending colon tissue from individuals with HαT (n = 4) as well as tissue and severity matched non-HαT controls (n = 4). Small intestinal biopsies were additionally analyzed using mass cytometry (CyTOF) from HαT individuals (n = 5) and non-HαT controls (n = 9). Droplet digital PCR (ddPCR) was used to establish TPSAB1 copy number variant for HαT detection. Comparisons across groups were performed using Welch's t-test with effect sizes and 95% CI.

Results: Across complementary platforms, HαT was associated with increased gastrointestinal mast cell abundance and elevated expression of mast cell activation markers, including CD203c, LAMP-1, and SIGLEC8. Both spatial transcriptomics and ddPCR demonstrated significantly increased MRGPRX2 and SIGLEC8 transcript levels in IBD samples from individuals with HαT compared with matched non-HαT IBD controls.

Discussion: These findings suggest that enhanced MRGPRX2 expression and mast cell activation may contribute to gastrointestinal symptoms in individuals with HαT, particularly in the setting of IBD. As interest in precision immunogenetics grows, defining mast cell phenotypes linked to α-tryptase copy number may help refine diagnostic evaluation and identify patients who could benefit from emerging mast cell-targeted therapeutic strategies in the context of IBD.

Introduction: Asthma is a multifactorial disease influenced by genetic and environmental factors, including diet. The gut microbiome contributes to airway inflammation via the gut-lung axis, partly through production of short chain fatty acids (SCFAs) from bacterial fermentation of dietary fiber. We hypothesized that dietary fiber supplementation could modulate the gut microbiome and increase SCFAs in children with asthma.

Methods: This is a double-blind, placebo-controlled trial of children who were randomized to consume 12 g of soluble corn fiber (SCF) as a supplement to their usual daily diet (50% the recommended daily fiber intake) or placebo for 4-6 weeks (clinicaltrials.gov NCT03673618). Dietary surveys, asthma symptom questionnaires, fecal, blood and nasal samples were collected before and after the intervention period to quantify fiber intake, asthma control, nasal and gut microbiome, and serum short chain fatty acids (SCFAs).

Results: Of the 20 children enrolled, 15 completed the intervention with an average adherence rate of 83%. SCFA concentrations and gut microbiome changes varied by individual and treatment group. No significant differences in gut or nasal alpha or beta diversity were observed between groups post-intervention. However, differential abundance analysis showed a trend toward increased Bifidobacterium in the SCF group compared to placebo (ANCOM-BC p = 0.0004, FDR q = 0.073).

Discussion: Supplementation of 50% of recommended daily fiber intake had minimal impact on asthma symptoms, the microbiome, or SCFA levels. Future studies should consider higher fiber doses, different fiber types, or targeting individuals with low baseline fiber intake to account for observed variability in microbiome and SCFA responses.

Clinical trial registration: https://clinicaltrials.gov/study/NCT03673618, identifier NCT03673618.

Background: Biological therapies have improved the control of severe asthma. However, biological therapies are expensive. Therefore, the cost-effective use of these medications after achieving improved disease control warrants consideration.

Methods: This retrospective case series analyzed 69 adult patients with asthma who received biological therapies at our department between 2009 and 2023. Among them, 11 patients underwent dosing interval extension. We collected data on their clinical characteristics, asthma control status, and changes in clinical parameters after interval extension.

Results: At the time of dosing interval extension, the mean patient age was 62.1 years, with 5 female patients. Omalizumab was used in five cases, benralizumab in five, and dupilumab in one. The dosing intervals were extended by 1.5 to 2 times. The median duration from the initiation of biologics to interval extension was 7.0 months, with 6 patients undergoing extension within the first 7 months. One year after extension, asthma exacerbation occurred in only one patient receiving omalizumab. The frequency of exacerbations and the proportion of patients receiving oral corticosteroids (OCS) were decreased. The median ACT score remained at 25, while the median daily OCS dose decreased from 5.0 mg to 4.0 mg (prednisolone equivalent). The median % predicted FEV₁ changed from 84.9% to 78.3%.

Conclusions: For patients whose asthma control improves after initiating biological therapy, extending the dosing interval may be a feasible treatment option. Given the retrospective, single-center design and small sample size, these findings are exploratory and generate hypotheses that require validation in larger, prospective studies.

Background: Severe pediatric asthma is a heterogeneous, high-burden disease marked by variable corticosteroid responsiveness, frequent exacerbations, and substantial impairment in quality of life. Advances in airway immunobiology, particularly the delineation of type-2 (T2) pathways (IgE, IL-5, IL-4/IL-13) and epithelial alarmins, have enabled the development of targeted biologic therapies for biomarker-defined patient subgroups.

Objective: To synthesize current evidence on the efficacy and safety of biologic therapies for severe pediatric asthma and to translate biomarker-driven selection into practical clinical guidance, while outlining emerging therapeutic directions.

Summary of findings: Targeted biologics, anti-IgE (omalizumab), anti-IL-5/IL-5Rα (mepolizumab, benralizumab; pediatric data for reslizumab remain limited), anti-IL-4Rα (dupilumab), and anti-TSLP (tezepelumab) improve disease control, reduce severe exacerbations, and enable steroid-sparing in appropriately selected children. Benefits are greatest in T2-high profiles, particularly with elevated blood eosinophils and/or fractional exhaled nitric oxide (FeNO), while tezepelumab shows efficacy across biomarker strata. Lung-function gains are modest to moderate but clinically meaningful. Persisting gaps include optimal treatment duration, stopping rules, long-term safety, cost, and equitable access.

Conclusions: Biologic therapies have reshaped the care of severe pediatric asthma, operationalizing precision medicine through immunologic endotyping and biomarker-guided selection. Priorities now include standardized definitions of response and remission, robust long-term safety data, and strategies to ensure equitable access across diverse pediatric populations.