M Á López-Matas, L Martín-López, F Vílchez-Sánchez, M Pedrosa, R Rodríguez-Pérez, J Domínguez-Ortega, J Carnés
{"title":"Bioinformatics-Based Prediction of B- and T-Cell Epitopes in R-Mandelonitrile Lyase, a Recently Described Peach Allergen.","authors":"M Á López-Matas, L Martín-López, F Vílchez-Sánchez, M Pedrosa, R Rodríguez-Pérez, J Domínguez-Ortega, J Carnés","doi":"10.18176/jiaci.1052","DOIUrl":"10.18176/jiaci.1052","url":null,"abstract":"","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"220-222"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V Tubita, P Mir Ihara, M F González-Matamala, C Picado, R M Muñoz Cano
{"title":"Prostaglandin E2: A Potential Link Between NSAIDs and the Menstrual Cycle, Cofactors of Food-Dependent Anaphylaxis.","authors":"V Tubita, P Mir Ihara, M F González-Matamala, C Picado, R M Muñoz Cano","doi":"10.18176/jiaci.1070","DOIUrl":"10.18176/jiaci.1070","url":null,"abstract":"<p><p>Food-induced anaphylaxis presents a significant health risk, accounting for 25% to 50% of adult allergic reactions. The variability in severity, even with identical allergen exposure (dose and allergen), suggests the involvement of other factors (cofactors) in exacerbation of allergic responses. Cofactors may function in 2 ways: by lowering the reaction threshold, ensuring patients remain asymptomatic in the absence of the cofactor and only experience symptoms when it is present; or by increasing severity, enabling patients with mild symptoms to endure a stronger reaction in the presence of the cofactor. Two cofactors have emerged, namely, nonsteroidal anti-inflammatory drugs (NSAIDs), which are well documented, and the menstrual cycle, which has received less attention. However, their intricate interplay has not yet been elucidated. Widely used for their anti-inflammatory properties, NSAIDs disrupt gastrointestinal integrity, reduce synthesis of prostaglandin E2 (PGE2) by inhibiting the enzyme cyclooxygenase (COX), and participate in mast cell activation, thus exacerbating food allergy symptoms. Similarly, the hormonal fluctuations during the menstrual cycle affect the COX pathway, modulating mast cell activation and allergic sensitivities. PGE2, a key mediator in immune modulation, plays a crucial role in maintaining immune homeostasis and suppressing mast cell activation. This review examines the potential role of PGE2 as a plausible link between NSAIDs and menstruation as cofactors in food allergy, suggesting a central role in modulating allergic sensitivities.</p>","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"155-169"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Deep Intronic Polymorphism at 9q21.11 Contributes to the Risk of Atopic Dermatitis Through Methylation-Regulated Expression of Tight Junction Protein 2.","authors":"Y Ye Lim, Y Y Sio, Y H Say, K Reginald, F T Chew","doi":"10.18176/jiaci.0978","DOIUrl":"10.18176/jiaci.0978","url":null,"abstract":"<p><strong>Background and objective: </strong>Atopic dermatitis (AD) is a chronic inflammatory itchy skin condition. Genome- and epigenome-wide association studies provide insights into genetic susceptibility and the pathogenesis of potential underlying disease. This study sought to functionally characterize an AD-associated single-nucleotide polymorphism (SNP) located deep intronic of the tight junction protein 2 (TJP2) gene (9q21.11 locus), identified through a genome-wide association study (GWAS).</p><p><strong>Methods: </strong>The association between the 9q21.11 locus (rs7872806) and AD was identified through a GWAS of 956 cases and 723 controls. TJP2 expression in peripheral blood mononuclear cells (PBMCs) was assessed against the rs7872806 genotype. Allele-specific methylation was evaluated at CpG sites 10 kb up- and down-stream of the 9q21.11 locus. The effect of DNA methylation on TJP2 expression was validated via in vitro methylation and 5-aza-2'-deoxycytidine-induced transcriptional activation studies. Transepidermal water loss (TEWL) measurements were used to determine skin barrier function.</p><p><strong>Results: </strong>The major allele \"G\" of rs7872806 was found to increase the risk of AD by 2.64-fold (adjusted P value, 2.40 × 10-18; OR, 0.38) and was associated with increased methylation levels at the cg13920460 site (P<.001) and lower TJP2 expression in PBMCs (Pearson P=1.09 × 10-6, Pearson R, -0.313, P<.001). Inhibition of methylation by 5-aza-2'-deoxycytidine increased TJP2 promoter activity by up to 85%. Elimination of the cg13920460 methylation site increased expression by approximately 25%. The major allele of rs7872806 was also found to be associated with increased TEWL (P<.001).</p><p><strong>Conclusion: </strong>Epigenetic influence at CpG site cg13920460 is associated with rs7872806 located deep intronic at 9q21.11. The SNP confers susceptibility to AD by altering TJP2 expression and promoting TEWL.</p>","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"179-193"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138811904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J Bernaola, M Otal-Buesa, B Barroso, M Valverde-Monge, J Sastre
{"title":"Revisiting the Impact of Misdiagnosed Drug Hypersensitivity in Hospitalized Patients: A 10-Year Perspective.","authors":"J Bernaola, M Otal-Buesa, B Barroso, M Valverde-Monge, J Sastre","doi":"10.18176/jiaci.1056","DOIUrl":"10.18176/jiaci.1056","url":null,"abstract":"","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"223-224"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Tomás-Pérez, J Domenech-Witek, M R Ávila-Castellano, C Carballas-Vázquez, A A Vásquez-Bautista, V Jover-Cerdá, R González-Mendiola
{"title":"Position Paper on the Treatment of Eosinophilic Esophagitis With Dupilumab.","authors":"M Tomás-Pérez, J Domenech-Witek, M R Ávila-Castellano, C Carballas-Vázquez, A A Vásquez-Bautista, V Jover-Cerdá, R González-Mendiola","doi":"10.18176/jiaci.1038","DOIUrl":"10.18176/jiaci.1038","url":null,"abstract":"<p><p>Eosinophilic esophagitis (EoE) is a chronic allergic condition affecting the esophagus and driven by food antigens. Many individuals diagnosed with EoE have other allergic conditions, such as food allergy, asthma, allergic rhinitis, and atopic dermatitis. The clinical goals of therapy in EoE include symptomatic, histologic, and endoscopic remission. The current paradigm for the treatment of EoE in Spain includes proton pump inhibitors, swallowed topical corticosteroids, and food elimination diets. These treatments have proven very effective in clinical studies. In April 2024, the Spanish Agency for Medicines and Medical Products approved dupilumab as the second drug for the treatment of EoE, thus adding this biologic to the therapeutic arsenal in EoE. The present review includes a positioning statement by the authors, all of whom are members of the Spanish Society of Allergy and Clinical Immunology Food-EoE Working Group.</p>","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"170-178"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V Paradis, A Des Roches, C Elbany, C Braun, F J Graham, K Samaan, R Labrosse, L Paradis, P Bégin
{"title":"Use of a 24-Hour Hotline vs Voicemail for Off-Hour Support During Oral Immunotherapy for Food Allergy.","authors":"V Paradis, A Des Roches, C Elbany, C Braun, F J Graham, K Samaan, R Labrosse, L Paradis, P Bégin","doi":"10.18176/jiaci.1063","DOIUrl":"10.18176/jiaci.1063","url":null,"abstract":"","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"227-229"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Blank, B Dorn, P Seiringer, J Grosch, B O Slusarenko, M Dittmar, R Kaczmarcyk, D Rogner, A Jung, L Plail, B Eberlein, T Biedermann, U Darsow, K Brockow, C B Schmidt-Weber, T Jakob
{"title":"Component-Resolved IgE and IgG4 Profiling Reveals Robust IgG4 Responses Primarily to Abundant Hymenoptera Allergens During Venom Immunotherapy and in Beekeepers.","authors":"S Blank, B Dorn, P Seiringer, J Grosch, B O Slusarenko, M Dittmar, R Kaczmarcyk, D Rogner, A Jung, L Plail, B Eberlein, T Biedermann, U Darsow, K Brockow, C B Schmidt-Weber, T Jakob","doi":"10.18176/jiaci.1072","DOIUrl":"https://doi.org/10.18176/jiaci.1072","url":null,"abstract":"<p><strong>Background and objectives: </strong>Venom immunotherapy (VIT) and natural exposure to Hymenoptera venom induce immune tolerance in allergic patients and beekeepers, respectively. Specific IgE (sIgE) and IgG4 (sIgG4) antibodies play crucial roles in allergic reactions and immune tolerance. To investigate the dynamics of sIgE and sIgG4 responses to Hymenoptera venom in patients undergoing VIT and in nonallergic beekeepers at a component-resolved level.</p><p><strong>Methods: </strong>Serum samples from patients allergic to honeybee venom (HBV) or yellow jacket venom (YJV) and from beekeepers were collected during the first year of VIT and before and after the beekeeping season, respectively. sIgE and sIgG4 levels to whole venom and molecular allergens were measured using the ImmunoCAP platform.</p><p><strong>Results: </strong>Pronounced sIgE and sIgG4 responses to Ves v 1 and 5 in YJV-allergic patients were accompanied by more frequent sensitization to Ves v 1 after up-dosing. While sIgE profiles in HBV-allergic patients were highly diverse, with a marked contribution of Api m 1 and Api m 10 sIgE, the sIgG4 response during VIT was strongly dominated by Api m 1. Different VIT preparations did not significantly affect the sIgG4 response to low-abundance HBV allergens. In beekeepers, induction of sIgG4 was dependent on sting frequency and was dominated by Api m 1.</p><p><strong>Conclusions: </strong>Robust induction of IgG4 during VIT and natural venom exposure occurs primarily to abundant allergens and is unaffected by the choice of VIT preparation. The effectiveness of VIT and beekeepers´ tolerance to HBV indicate that strong sIgG4 responses to lowabundance allergens are not crucial for immune tolerance.</p>","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"0"},"PeriodicalIF":6.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Morejón, S Quirce, J Domínguez-Ortega, D Romero, A Noblejas, J J Ríos-Blanco, L De Las Vecillas
{"title":"Mepolizumab as an Effective Alternative to Immunosuppressive and Teratogenic Therapies for the Early Treatment of EGPA: A Case Report.","authors":"L Morejón, S Quirce, J Domínguez-Ortega, D Romero, A Noblejas, J J Ríos-Blanco, L De Las Vecillas","doi":"10.18176/jiaci.1087","DOIUrl":"https://doi.org/10.18176/jiaci.1087","url":null,"abstract":"","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"0"},"PeriodicalIF":6.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V I Hinkkanen, T Savinko, K Palosuo, H Alenius, M J Mäkelä, P Karisola
{"title":"Regular Allergen Exposure During Oral Immunotherapy Alters the Transcriptomic Innate Immune Response After Cellular Restimulation in Children With Egg Allergy.","authors":"V I Hinkkanen, T Savinko, K Palosuo, H Alenius, M J Mäkelä, P Karisola","doi":"10.18176/jiaci.1079","DOIUrl":"https://doi.org/10.18176/jiaci.1079","url":null,"abstract":"<p><strong>Background and objectives: </strong>Oral immunotherapy (OIT) is a promising treatment for food allergies. However, the molecular mechanisms leading to desensitization remain unknown. To better understand the immunological mechanisms and transcriptional changes underlying desensitization to food allergens during OIT.</p><p><strong>Methods: </strong>Our cohort consisted of 40 Finnish children with egg allergy who underwent OIT. Peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, and 8 months of therapy and stimulated with an egg allergen extract. Differentially expressed genes (DEGs) were identified based on quantile-normalized and batch-corrected microarray data using a linear model. Gene enrichment and Pearson correlation analyses were conducted.</p><p><strong>Results: </strong>After 8 months of therapy, 45% of patients were fully desensitized and 55% partially desensitized. Stimulation with egg yielded 49 DEGs at 0 months, 723 DEGs at 3 months, and 759 DEGs at 8 months in PBMCs after comparison with unstimulated controls. At 8 months of OIT, allergen stimulation led to down regulation of proinflammatory pathways, as well as IL-4 and IL-13 signaling. At baseline, the immune response in the fully desensitized group was more reactive than in the partially desensitized group.</p><p><strong>Conclusions: </strong>During OIT, general immune activity is increased, especially the number of down-regulated genes, suggesting active immune suppression. Transcriptomic profiles differ between fully and partially desensitized patients, with a notably more reactive immune response in the fully desensitized group at baseline. Innate immunity seems to play a significant role in the development of desensitization during OIT.</p>","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"0"},"PeriodicalIF":6.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O Domínguez, C Riggioni, E Poyatos, R M Jiménez-Feijoo, M Piquer, A Machinena, M Folqué, I Ortiz de Landazuri, M Torradeflot, J Lozano, L Alsina, M Pascal, M Alvaro-Lozano
{"title":"Biomarkers of Tolerance to Baked Milk in Cow's Milk-Allergic Children at High Risk of Anaphylaxis.","authors":"O Domínguez, C Riggioni, E Poyatos, R M Jiménez-Feijoo, M Piquer, A Machinena, M Folqué, I Ortiz de Landazuri, M Torradeflot, J Lozano, L Alsina, M Pascal, M Alvaro-Lozano","doi":"10.18176/jiaci.1074","DOIUrl":"https://doi.org/10.18176/jiaci.1074","url":null,"abstract":"<p><strong>Background and objectives: </strong>Consuming baked milk (BM) may accelerate tolerance in cow's milk-allergic (CMA) children. In high-risk patients, controlled BM-based oral food challenge (BM-OFC) is recommended, as the benefits can outweigh the risks of a prolonged exclusion diet. To identify predictive biomarkers for BM-OFC outcomes in a cohort at high risk of anaphylaxis and compare the OFC thresholds for baked and pasteurized cow´s milk protein (CMP).</p><p><strong>Methods: </strong>We performed a prospective study of children (≥12 months to <6 years) with a history of CMA. Testing at diagnosis involved prick testing, specific IgE (sIgE) for CM and components, sIgG4, and the basophil activation test (BAT). Patients underwent a BM-OFC aiming for a cumulative dose of 1 g of CM protein. BM-tolerant children subsequently underwent a CM-OFC to confirm CMA.</p><p><strong>Results: </strong>The study population comprised 50 patients (66% with a history of anaphylaxis). A reaction was recorded during BM-OFC in 36% of patients (39% with anaphylaxis). The median reactivity threshold was 138 mg of CMP. Risk factors for BM allergy included history of anaphylaxis, age >3 years, elevated CM-sIgE and casein-sIgE, and a positive BAT result. The cut-offs were as follows: >5 mm for skin prick testing with casein, ≥8.5 kUA/L for CM-sIgE, and ≥5.7 kUA/L for casein-sIgE. These made it possible to distinguish BM-allergic patients from CMA patients who tolerated BM. Among BM-tolerant patients, the CM-OFC threshold was 270 mg, with 43.8% reacting to <100 mg (40% with anaphylaxis).</p><p><strong>Conclusions: </strong>BM-OFC is not risk-free. Nevertheless, two-thirds of high-risk CMA children were BM-tolerant and benefited from early introduction of BM products. Patient selection can be guided by biomarkers and a prior history of anaphylaxis to baked goods. The reactivity threshold to pasteurized milk was less than half of the tolerated dose of BM (1000 mg).</p>","PeriodicalId":50173,"journal":{"name":"Journal of Investigational Allergology and Clinical Immunology","volume":" ","pages":"0"},"PeriodicalIF":6.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}