Sung-Ryeol Kim, Da Eun Lee, Hyun Young Jung, In-Wha Kim, Hye-Ryun Kang, Kyung Hee Park, Jung-Won Park, Jung-Mi Oh, Jae-Hyun Lee
Background
Cefaclor is a commonly prescribed β-lactam antibiotic and a known major cause of immediate-type drug hypersensitivity in Korea. However, its genetic risk factors remain poorly understood. We aimed to identify genetic variants associated with cefaclor-induced anaphylaxis and evaluate their potential clinical implications.
Methods
Whole-exome sequencing and HLA genotyping were performed in 33 patients with cefaclor-induced anaphylaxis and 41 drug-tolerant controls. Associations were assessed using logistic regression. Selected variants were validated in an independent Korean population. Gene set enrichment analysis (GSEA) was performed using association statistics from all variants to investigate relevant biological pathways.
Results
A rare missense variant, rs765144578 in TPSAB1 was strongly associated with anaphylaxis and remained significant in the validation control group. It was found in 90.91% of patients with hypotension, suggesting a link to reaction severity. Rs192498095 in HLA-DRB5 showed a significant association in the discovery cohort. However, it was not detected in the replication set, likely due to its rarity and polymorphic nature. Co-occurrence of rs765144578 in TPSAB1 and rs192498095 in HLA-DRB5 markedly increased risk. GSEA revealed significant enrichment of the TNF-α signaling via NF-κB pathway, reflecting pathway-level immune activation.
Conclusion
Genetic variants in TPSAB1 and HLA-DRB5 may contribute to the risk of cefaclor-induced anaphylaxis, and TPSAB1 may also be associated with severity. These findings may support the development of future screening strategies or individualized risk prediction models in β-lactam allergy.
{"title":"Identifying Genetic Variants in Patients With Cefaclor-Induced Anaphylaxis Using Human Leukocyte Antigen Typing and Whole-Exome Sequencing","authors":"Sung-Ryeol Kim, Da Eun Lee, Hyun Young Jung, In-Wha Kim, Hye-Ryun Kang, Kyung Hee Park, Jung-Won Park, Jung-Mi Oh, Jae-Hyun Lee","doi":"10.1002/clt2.70103","DOIUrl":"10.1002/clt2.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cefaclor is a commonly prescribed β-lactam antibiotic and a known major cause of immediate-type drug hypersensitivity in Korea. However, its genetic risk factors remain poorly understood. We aimed to identify genetic variants associated with cefaclor-induced anaphylaxis and evaluate their potential clinical implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-exome sequencing and HLA genotyping were performed in 33 patients with cefaclor-induced anaphylaxis and 41 drug-tolerant controls. Associations were assessed using logistic regression. Selected variants were validated in an independent Korean population. Gene set enrichment analysis (GSEA) was performed using association statistics from all variants to investigate relevant biological pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A rare missense variant, rs765144578 in <i>TPSAB1</i> was strongly associated with anaphylaxis and remained significant in the validation control group. It was found in 90.91% of patients with hypotension, suggesting a link to reaction severity. Rs192498095 in HLA-DRB5 showed a significant association in the discovery cohort. However, it was not detected in the replication set, likely due to its rarity and polymorphic nature. Co-occurrence of rs765144578 in <i>TPSAB1</i> and rs192498095 in <i>HLA-DRB5</i> markedly increased risk. GSEA revealed significant enrichment of the TNF-α signaling via NF-κB pathway, reflecting pathway-level immune activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Genetic variants in <i>TPSAB1</i> and <i>HLA-DRB5</i> may contribute to the risk of cefaclor-induced anaphylaxis, and <i>TPSAB1</i> may also be associated with severity. These findings may support the development of future screening strategies or individualized risk prediction models in β-lactam allergy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reshed Abohalaka, Selin Ercan, Lauri Lehtimäki, Saliha Selin Özuygur Ermis, Daniil Lisik, Muwada Bashir Awad Bashir, Radhika Jadhav, Linda Ekerljung, Göran Wennergren, Jan Lötvall, Teet Pullerits, Helena Backman, Madeleine Rådinger, Bright I. Nwaru, Hannu Kankaanranta
Background
Fractional exhaled nitric oxide (FENO) is used to differentiate asthma inflammatory phenotypes and guide its management. However, data on FENO reference values in a representative adult population is limited. We aim to derive reference values and determinants of FENO in a representative adult population.
Methods
The West Sweden Asthma Study is a clinical-epidemiological population-representative study of randomly selected adults in Western Sweden. From this cohort, 943 subjects participated in comprehensive clinical investigations, including skin prick testing (SPT), specific immunoglobulin E (sIgE) analysis, and FENO measurement. Clinical allergy was defined as co-occurrence of atopy (positivity to SPT or sIgE) and self-reported allergic symptoms to the same allergen family. FENO levels were analysed in relation to the presence or absence of clinical allergy, asthma, and other factors.
Results
The 95th percentile of FENO ranged from 34 parts per billion (ppb) in those between 30 and 40 years old to 52 ppb in those ≤ 30 years old in the entire sample (N = 943), and from 26 to 37 ppb in those without clinical allergy, asthma, or chronic obstructive pulmonary disease (COPD) (n = 587), depending on age. Sex, smoking, clinical allergy, atopy, asthma, and hypertension influenced FENO levels, meanwhile, age, asthma, clinical allergy, and reversibility-related variables were significant determinants of FENO levels.
Conclusion
The 95th percentile (upper normal limit) for FENO ranges from 34 to 52 ppb overall, and from 26 to 37 ppb in those without clinical allergy, asthma, or COPD, depending on age. These findings provide a guide for interpreting FENO in the general population.
{"title":"Reference Values and Determinants of Fractional Exhaled Nitric Oxide in a Representative Adult Population in Western Sweden","authors":"Reshed Abohalaka, Selin Ercan, Lauri Lehtimäki, Saliha Selin Özuygur Ermis, Daniil Lisik, Muwada Bashir Awad Bashir, Radhika Jadhav, Linda Ekerljung, Göran Wennergren, Jan Lötvall, Teet Pullerits, Helena Backman, Madeleine Rådinger, Bright I. Nwaru, Hannu Kankaanranta","doi":"10.1002/clt2.70107","DOIUrl":"10.1002/clt2.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fractional exhaled nitric oxide (FE<sub>NO</sub>) is used to differentiate asthma inflammatory phenotypes and guide its management. However, data on FE<sub>NO</sub> reference values in a representative adult population is limited. We aim to derive reference values and determinants of FE<sub>NO</sub> in a representative adult population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The West Sweden Asthma Study is a clinical-epidemiological population-representative study of randomly selected adults in Western Sweden. From this cohort, 943 subjects participated in comprehensive clinical investigations, including skin prick testing (SPT), specific immunoglobulin E (sIgE) analysis, and FE<sub>NO</sub> measurement. Clinical allergy was defined as co-occurrence of atopy (positivity to SPT or sIgE) and self-reported allergic symptoms to the same allergen family. FE<sub>NO</sub> levels were analysed in relation to the presence or absence of clinical allergy, asthma, and other factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 95<sup>th</sup> percentile of FE<sub>NO</sub> ranged from 34 parts per billion (ppb) in those between 30 and 40 years old to 52 ppb in those ≤ 30 years old in the entire sample (<i>N</i> = 943), and from 26 to 37 ppb in those without clinical allergy, asthma, or chronic obstructive pulmonary disease (COPD) (<i>n</i> = 587), depending on age. Sex, smoking, clinical allergy, atopy, asthma, and hypertension influenced FE<sub>NO</sub> levels, meanwhile, age, asthma, clinical allergy, and reversibility-related variables were significant determinants of FE<sub>NO</sub> levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The 95<sup>th</sup> percentile (upper normal limit) for FE<sub>NO</sub> ranges from 34 to 52 ppb overall, and from 26 to 37 ppb in those without clinical allergy, asthma, or COPD, depending on age. These findings provide a guide for interpreting FE<sub>NO</sub> in the general population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maura M. Kere, Sophia Björkander, Simon Kebede Merid, Natalia Hernandez-Pacheco, Paul Maier, Anne-Sophie Merritt, Anna Bergström, Inger Kull, Carsten O. Daub, Jenny Mjösberg, Christopher Andrew Tibbitt, Erik Melén
Background
Investigation of T cell and innate lymphoid cell (ILC) subsets in type 2 (T2) and non-type 2 (non-T2) asthma are needed to elucidate disease mechanisms. In this study, we aimed to identify ILC, CD4+, and CD8+ T cell populations in blood that differentiate between T2 and non-T2 features in subjects with and without asthma.
Methods
The study population included 86 young adults selected from the Swedish population-based BAMSE cohort. Asthma and non-asthma subjects with sensitization to inhalant allergens and/or blood eosinophil count ≥ 0.3 × 109/L were classified into T2 groups. Non-T2 groups were defined by the absence of sensitization to inhalant allergens and blood eosinophil count < 0.3 × 109/L. PBMC samples underwent 18-parameter flow cytometry to identify ILC and CD4+ and CD8+ T cell populations. Logistic regression models were employed on normalized flow cytometry data after hierarchical clustering.
Results
A higher frequency of CD4+ CRTH2+ T memory cells was associated with T2 features independent of asthma status. The frequency of CD62L+ ILC2s was higher and CD4+ KLRG1+ central memory T cells was lower specifically in T2 asthma. Non-T2 asthma was associated with increased frequencies of CD45RO+ ILC2s and CD8+ memory T cells.
Conclusion
Our results suggest that T2 asthma and non-T2 asthma are characterized by distinct features related to ILC and T cell populations. Further investigation of particularly ILC and CD8+ T cell subsets in non-T2 asthma could offer a deeper understanding of underlying disease mechanisms for this endotype.
{"title":"Distinct Phenotypes of Peripheral Innate Lymphoid Cells and T Cells in Type 2 and Non-Type 2 Asthma","authors":"Maura M. Kere, Sophia Björkander, Simon Kebede Merid, Natalia Hernandez-Pacheco, Paul Maier, Anne-Sophie Merritt, Anna Bergström, Inger Kull, Carsten O. Daub, Jenny Mjösberg, Christopher Andrew Tibbitt, Erik Melén","doi":"10.1002/clt2.70108","DOIUrl":"10.1002/clt2.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Investigation of T cell and innate lymphoid cell (ILC) subsets in type 2 (T2) and non-type 2 (non-T2) asthma are needed to elucidate disease mechanisms. In this study, we aimed to identify ILC, CD4+, and CD8+ T cell populations in blood that differentiate between T2 and non-T2 features in subjects with and without asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study population included 86 young adults selected from the Swedish population-based BAMSE cohort. Asthma and non-asthma subjects with sensitization to inhalant allergens and/or blood eosinophil count ≥ 0.3 × 10<sup>9</sup>/L were classified into T2 groups. Non-T2 groups were defined by the absence of sensitization to inhalant allergens and blood eosinophil count < 0.3 × 10<sup>9</sup>/L. PBMC samples underwent 18-parameter flow cytometry to identify ILC and CD4+ and CD8+ T cell populations. Logistic regression models were employed on normalized flow cytometry data after hierarchical clustering.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A higher frequency of CD4+ CRTH2+ T memory cells was associated with T2 features independent of asthma status. The frequency of CD62L+ ILC2s was higher and CD4+ KLRG1+ central memory T cells was lower specifically in T2 asthma. Non-T2 asthma was associated with increased frequencies of CD45RO+ ILC2s and CD8+ memory T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest that T2 asthma and non-T2 asthma are characterized by distinct features related to ILC and T cell populations. Further investigation of particularly ILC and CD8+ T cell subsets in non-T2 asthma could offer a deeper understanding of underlying disease mechanisms for this endotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leszek Blicharz, Emilia Samborowska, Radosław Zagożdżon, Joanna Czuwara, Michał Zych, Aleksander Roszczyk, Michał Zaremba, Michał Dadlez, Zbigniew Samochocki, Małgorzata Olszewska, Lidia Rudnicka
Background
Gut microbiome dysbiosis may cause metabolic dysregulation and intestinal barrier impairment. The latter are hypothesized to provoke food allergy and aggravate cutaneous inflammation. Our objective was to determine the prevalence of food sensitization in adult patients with atopic dermatitis and relate it to the disease severity and the biomarkers of the gut-skin axis.
Methods
50 adult patients with atopic dermatitis and 25 controls were enrolled in this cross-sectional study. Disease severity was determined by using SCORAD and EASI scores. Liquid chromatography-mass spectrometry, Luminex, and Polycheck immunoassays were performed to detect serum concentrations of total IgE, food-specific IgEs, gut-derived metabolites, and leaky gut-related biomarkers.
Results
Food sensitization was significantly more prevalent in patients with atopic dermatitis than in the controls. The severity of atopic dermatitis (EASI, SCORAD) was higher in patients with food sensitization and correlated with the number of positive food-specific IgEs. Higher concentrations of total IgE and higher numbers of positive food-specific IgEs were associated with lower concentrations of short-chain fatty acids and higher concentrations of indoxyl and leaky gut-related biomarkers (LBP, syndecan-4, IL-10, IL-22).
Conclusion
The results suggest a relationship between food sensitization and the severity of atopic dermatitis. This could be partly associated with gut-derived metabolites and intestinal barrier impairment. Fiber-rich diet and restriction of protein could hold potential for upregulating short-chain fatty acids and downregulating indoxyl, which may translate to decreasing the likelihood of food sensitization in atopic dermatitis. Notably, the cross-sectional nature of this exploratory study limits the ability to draw causal inferences, which should be further examined in future prospective research.
{"title":"Food Sensitization Is Associated With Atopic Dermatitis Severity, Gut-Derived Metabolites and Leaky Gut in Adults","authors":"Leszek Blicharz, Emilia Samborowska, Radosław Zagożdżon, Joanna Czuwara, Michał Zych, Aleksander Roszczyk, Michał Zaremba, Michał Dadlez, Zbigniew Samochocki, Małgorzata Olszewska, Lidia Rudnicka","doi":"10.1002/clt2.70094","DOIUrl":"10.1002/clt2.70094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gut microbiome dysbiosis may cause metabolic dysregulation and intestinal barrier impairment. The latter are hypothesized to provoke food allergy and aggravate cutaneous inflammation. Our objective was to determine the prevalence of food sensitization in adult patients with atopic dermatitis and relate it to the disease severity and the biomarkers of the gut-skin axis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>50 adult patients with atopic dermatitis and 25 controls were enrolled in this cross-sectional study. Disease severity was determined by using SCORAD and EASI scores. Liquid chromatography-mass spectrometry, Luminex, and Polycheck immunoassays were performed to detect serum concentrations of total IgE, food-specific IgEs, gut-derived metabolites, and leaky gut-related biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Food sensitization was significantly more prevalent in patients with atopic dermatitis than in the controls. The severity of atopic dermatitis (EASI, SCORAD) was higher in patients with food sensitization and correlated with the number of positive food-specific IgEs. Higher concentrations of total IgE and higher numbers of positive food-specific IgEs were associated with lower concentrations of short-chain fatty acids and higher concentrations of indoxyl and leaky gut-related biomarkers (LBP, syndecan-4, IL-10, IL-22).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results suggest a relationship between food sensitization and the severity of atopic dermatitis. This could be partly associated with gut-derived metabolites and intestinal barrier impairment. Fiber-rich diet and restriction of protein could hold potential for upregulating short-chain fatty acids and downregulating indoxyl, which may translate to decreasing the likelihood of food sensitization in atopic dermatitis. Notably, the cross-sectional nature of this exploratory study limits the ability to draw causal inferences, which should be further examined in future prospective research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atopic Dermatitis (AD) is a chronic inflammatory skin condition characterized by intensely itchy eczematous lesions and dryness. Recent epidemiological studies have indicated a notable increase in the prevalence of AD in industrialized countries, suggesting that air pollution may significantly influence the onset and progression of AD.
Body
This review primarily describes the mechanistic roles of major air pollutants in the pathogenesis of AD, focusing particularly on oxidative stress, skin barrier dysfunction, and immune dysregulation. Moreover, the potential of targeting these pathways to prevent and manage AD is discussed.
Conclusion
Air pollution contributes to the pathogenesis of AD by inducing oxidative stress, skin barrier dysfunction, and immune dysregulation through pathways such as AhR and NF-κB. Mitigating its impact necessitates both personal protective measures and public health policies. Future research should investigate pollutant-climate interactions and develop novel therapies targeting these mechanisms.
{"title":"The Role of Air Pollution in the Pathogenesis of Atopic Dermatitis, With a Focus on Oxidative Stress","authors":"Chen-Xi Liu, Li Li, Yue-Ping Zeng","doi":"10.1002/clt2.70104","DOIUrl":"10.1002/clt2.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atopic Dermatitis (AD) is a chronic inflammatory skin condition characterized by intensely itchy eczematous lesions and dryness. Recent epidemiological studies have indicated a notable increase in the prevalence of AD in industrialized countries, suggesting that air pollution may significantly influence the onset and progression of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Body</h3>\u0000 \u0000 <p>This review primarily describes the mechanistic roles of major air pollutants in the pathogenesis of AD, focusing particularly on oxidative stress, skin barrier dysfunction, and immune dysregulation. Moreover, the potential of targeting these pathways to prevent and manage AD is discussed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Air pollution contributes to the pathogenesis of AD by inducing oxidative stress, skin barrier dysfunction, and immune dysregulation through pathways such as AhR and NF-κB. Mitigating its impact necessitates both personal protective measures and public health policies. Future research should investigate pollutant-climate interactions and develop novel therapies targeting these mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12437320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allergic rhinitis (AR) is a common allergic airway disease. Although B cells play essential roles in AR pathogenesis, their subset distribution outside the allergen exposure period remains poorly characterized.
Objective
To profile peripheral blood B cell subsets in AR patients during the pollen-free season and compare them with healthy controls (HC), aiming to identify persistent immunological alterations and potential biomarkers.
Methods
Peripheral blood mononuclear cells (PBMCs) were collected from a total of 28 participants, 14 patients with allergic rhinitis (AR) and 14 healthy controls (HC) during the off-season. B cell subsets were identified using flow cytometry based on IgD and CD27 expression, classifying cells as naïve (IgD+CD27−), unswitched memory (IgD+CD27+), switched/conventional memory (IgD−CD27+), and unconventional memory B cells (IgD−CD27−). CD38 and CD24 were utilized to further distinguish transitional, naïve, memory, and plasma cell phenotypes. Immunoglobulin isotypes (IgG1-4, IgA1+/IgA2+) were assessed specifically within conventional memory B cells, while CD86 expression was evaluated on IgM+ memory-like and naïve B cells. Additionally, kappa (κ) and lambda (λ) light chain usage was analyzed to assess light chain distribution.
Results
AR patients displayed lower frequencies of IgG1+, IgG2+, and IgA1+/IgA2+ memory B cells, along with elevated frequencies of IgG4+ and κ+ B cells. Additionally, CD86+IgM+ memory-like B cells were significantly reduced in AR, suggesting altered activation dynamics. No significant differences were observed in CD24/CD38 profiling.
Conclusion
Even outside allergen exposure, AR patients exhibit systemic B cell dysregulation, characterized by skewed class switching, altered subset distribution, and reduced activation markers expression. These findings underscore persistent immune imbalance in AR, identify potential off-season biomarkers of allergic inflammation.
{"title":"Persistent Off-Season Dysregulation of Memory B Cell Subsets in Allergic Rhinitis","authors":"Maryam Jafari, Eric Hjalmarsson, Laila Hellkvist, Eirini Paziou, Agnetha Karlsson, Susanna Kumlien Georén, Lars-Olaf Cardell","doi":"10.1002/clt2.70100","DOIUrl":"https://doi.org/10.1002/clt2.70100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Allergic rhinitis (AR) is a common allergic airway disease. Although B cells play essential roles in AR pathogenesis, their subset distribution outside the allergen exposure period remains poorly characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To profile peripheral blood B cell subsets in AR patients during the pollen-free season and compare them with healthy controls (HC), aiming to identify persistent immunological alterations and potential biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells (PBMCs) were collected from a total of 28 participants, 14 patients with allergic rhinitis (AR) and 14 healthy controls (HC) during the off-season. B cell subsets were identified using flow cytometry based on IgD and CD27 expression, classifying cells as naïve (IgD<sup>+</sup>CD27<sup>−</sup>), unswitched memory (IgD<sup>+</sup>CD27<sup>+</sup>), switched/conventional memory (IgD<sup>−</sup>CD27<sup>+</sup>), and unconventional memory B cells (IgD<sup>−</sup>CD27<sup>−</sup>). CD38 and CD24 were utilized to further distinguish transitional, naïve, memory, and plasma cell phenotypes. Immunoglobulin isotypes (IgG1-4, IgA1<sup>+</sup>/IgA2<sup>+</sup>) were assessed specifically within conventional memory B cells, while CD86 expression was evaluated on IgM<sup>+</sup> memory-like and naïve B cells. Additionally, kappa (<i>κ</i>) and lambda (<i>λ</i>) light chain usage was analyzed to assess light chain distribution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AR patients displayed lower frequencies of IgG1<sup>+</sup>, IgG2<sup>+</sup>, and IgA1<sup>+</sup>/IgA2<sup>+</sup> memory B cells, along with elevated frequencies of IgG4<sup>+</sup> and κ<sup>+</sup> B cells. Additionally, CD86<sup>+</sup>IgM<sup>+</sup> memory-like B cells were significantly reduced in AR, suggesting altered activation dynamics. No significant differences were observed in CD24/CD38 profiling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Even outside allergen exposure, AR patients exhibit systemic B cell dysregulation, characterized by skewed class switching, altered subset distribution, and reduced activation markers expression. These findings underscore persistent immune imbalance in AR, identify potential off-season biomarkers of allergic inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela Trąd-Wójcik, Piotr Szatkowski, Adam Ćmiel, Radosław Kacorzyk, Adam Stępień, Lucyna Mastalerz
Background
Induced sputum cell count is crucial for assessing airway inflammatory phenotypes. This study investigated how aspirin-induced bronchospasm affects sputum cell counts in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), comparing systemic versus local aspirin administration.
Methods
Seventy-eight patients with N-ERD and 39 with aspirin-tolerant asthma (ATA) participated. In the N-ERD group, induced sputum was collected before aspirin challenge and during aspirin-induced bronchospasm. We assessed changes in the percentages of eosinophils, neutrophils, lymphocytes, and macrophages, and airway inflammatory phenotypes classified by sputum cells into: (A) eosinophilic, neutrophilic, paucigranulocytic, and mixed; and (B) eosinophilic and noneosinophilic.
Results
Baseline sputum neutrophil percentage was lower in the N-ERD than in the ATA (32.9% ± 20.8% vs. 41.6% ± 22.5%; p = 0.02). Inflammatory phenotypes at baseline differed between groups in both classifications (A: p = 0.041; B: p = 0.044). In the N-ERD group, sputum eosinophil percentage decreased after both oral (8.9% ± 11.6% vs. 6.1% ± 8.9%, p = 0.009) and inhaled (10.4% ± 16.1% vs. 4.8% ± 6.3%, p = 0.045) challenges, without altering inflammatory phenotypes. The ATA group showed no changes. Sputum macrophage percentage dropped after oral challenge in both groups (N-ERD: 40.5% ± 18.5% vs. 35.6% ± 21.5%; p = 0.004; ATA: 36.5% ± 23.6% vs. 26.7% ± 20.4%; p = 0.0003). In the N-ERD group, baseline sputum lymphocyte and eosinophil percentages were inversely correlated with the provocative dose of aspirin that resulted in a 20% decrease in baseline forced expiratory volume in 1 s following oral aspirin challenge (R = −0.31, p = 0.02 and R = −0.33, p = 0.02, respectively).
Conclusion
In N-ERD, sputum eosinophil percentage decreased after aspirin challenge regardless of administration route. In both N-ERD and ATA, sputum macrophage percentage decreased after oral aspirin challenge.
诱导痰细胞计数是评估气道炎症表型的关键。本研究探讨了非甾体抗炎药加重呼吸系统疾病（N-ERD）患者阿司匹林诱导的支气管痉挛对痰细胞计数的影响，比较了全身和局部阿司匹林给药。方法对78例N-ERD患者和39例阿斯匹林耐受性哮喘（ATA）患者进行研究。在N-ERD组，在阿司匹林刺激前和阿司匹林引起的支气管痉挛期间收集诱导痰。我们评估了嗜酸性粒细胞、中性粒细胞、淋巴细胞和巨噬细胞百分比的变化，以及按痰细胞分类的气道炎症表型：(A)嗜酸性粒细胞、嗜中性粒细胞、少粒细胞和混合型；(B)嗜酸性和非嗜酸性。结果N-ERD组痰中性粒细胞基线百分比低于ATA组（32.9%±20.8% vs 41.6%±22.5%;p = 0.02）。两组的炎症表型在基线时存在差异（A: p = 0.041; B: p = 0.044）。在N-ERD组，口服（8.9%±11.6% vs. 6.1%±8.9%,p = 0.009）和吸入（10.4%±16.1% vs. 4.8%±6.3%,p = 0.045）刺激后痰嗜酸性粒细胞百分比下降，未改变炎症表型。ATA组没有变化。两组口腔攻毒后痰中巨噬细胞百分比均下降（N-ERD: 40.5%±18.5% vs. 35.6%±21.5%,p = 0.004; ATA: 36.5%±23.6% vs. 26.7%±20.4%,p = 0.0003）。在N-ERD组中，基线痰淋巴细胞和嗜酸性粒细胞百分比与阿司匹林刺激剂量呈负相关，阿司匹林刺激剂量导致口服阿司匹林刺激后1 s内基线用力呼气量减少20% （R = - 0.31, p = 0.02和R = - 0.33, p = 0.02）。结论在N-ERD中，不论给药途径如何，阿司匹林刺激后痰嗜酸性粒细胞百分比均下降。在N-ERD和ATA中，口服阿司匹林后痰中巨噬细胞百分比下降。
{"title":"Sputum Eosinophil and Macrophage Changes After Aspirin Challenge in Patients With Nonsteroidal Anti-Inflammatory Drug–Exacerbated Respiratory Disease","authors":"Gabriela Trąd-Wójcik, Piotr Szatkowski, Adam Ćmiel, Radosław Kacorzyk, Adam Stępień, Lucyna Mastalerz","doi":"10.1002/clt2.70079","DOIUrl":"https://doi.org/10.1002/clt2.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Induced sputum cell count is crucial for assessing airway inflammatory phenotypes. This study investigated how aspirin-induced bronchospasm affects sputum cell counts in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), comparing systemic versus local aspirin administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy-eight patients with N-ERD and 39 with aspirin-tolerant asthma (ATA) participated. In the N-ERD group, induced sputum was collected before aspirin challenge and during aspirin-induced bronchospasm. We assessed changes in the percentages of eosinophils, neutrophils, lymphocytes, and macrophages, and airway inflammatory phenotypes classified by sputum cells into: (A) eosinophilic, neutrophilic, paucigranulocytic, and mixed; and (B) eosinophilic and noneosinophilic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline sputum neutrophil percentage was lower in the N-ERD than in the ATA (32.9% ± 20.8% vs. 41.6% ± 22.5%; <i>p</i> = 0.02). Inflammatory phenotypes at baseline differed between groups in both classifications (A: <i>p</i> = 0.041; B: <i>p</i> = 0.044). In the N-ERD group, sputum eosinophil percentage decreased after both oral (8.9% ± 11.6% vs. 6.1% ± 8.9%, <i>p</i> = 0.009) and inhaled (10.4% ± 16.1% vs. 4.8% ± 6.3%, <i>p</i> = 0.045) challenges, without altering inflammatory phenotypes. The ATA group showed no changes. Sputum macrophage percentage dropped after oral challenge in both groups (N-ERD: 40.5% ± 18.5% vs. 35.6% ± 21.5%; <i>p</i> = 0.004; ATA: 36.5% ± 23.6% vs. 26.7% ± 20.4%; <i>p</i> = 0.0003). In the N-ERD group, baseline sputum lymphocyte and eosinophil percentages were inversely correlated with the provocative dose of aspirin that resulted in a 20% decrease in baseline forced expiratory volume in 1 s following oral aspirin challenge (<i>R</i> = −0.31, <i>p</i> = 0.02 and <i>R</i> = −0.33, <i>p</i> = 0.02, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In N-ERD, sputum eosinophil percentage decreased after aspirin challenge regardless of administration route. In both N-ERD and ATA, sputum macrophage percentage decreased after oral aspirin challenge.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simone Colosimo, Cristiana Indolfi, Vittoria Frattolillo, Gianluca Mondillo, Alessandra Perrotta, Mariapia Masino, Fabio Decimo, Michele Miraglia del Giudice
Background
Fel d 1, the primary allergen produced by cats, is a glycoprotein found mainly in their salivary and sebaceous glands. Due to its small size and stability, it easily becomes airborne and adheres to surfaces, posing a persistent problem for allergic individuals.
Methods
This article reviews innovative strategies aimed at reducing Fel d 1 expression and exposure and mitigating its allergic effects on humans.
Results
A key approach involves dietary supplementation with chicken egg-derived IgY antibodies specific to Fel d 1. These antibodies neutralize the allergen in the saliva, significantly reducing its transfer to the fur and environmental presence, with clinical studies showing a notable decrease in nasal symptoms among allergic individuals. Additional dietary factors, such as omega-3 fatty acids, polyphenols, and low-glycemic index foods, may further modulate allergen production via hormonal and sebaceous pathways. Immunotherapy options include the Fel-CuMV vaccine for cats and human-targeted treatments with monoclonal antibodies like REGN1908-1909, both of which demonstrate significant reductions in allergic symptoms. Genetic modification and hormonal manipulation (e.g., neutering) offer further avenues to lower Fel d 1 expression. Environmental strategies, including HEPA filters and protease treatments, can also help reduce allergen load in households.
Conclusions
Together, these approaches form a multifaceted framework for managing cat allergies, potentially allowing allergic individuals to coexist with their pets. Future research should aim to optimize these interventions and explore synergistic combinations to achieve more effective and personalized allergy management.
Key Message
This review summarizes innovative methods for reducing Fel d 1 production in cats, including genetic, immunological and dietary approaches, with potential implications for allergy prevention in humans.
猫产生的主要过敏原feld1是一种糖蛋白，主要存在于猫的唾液腺和皮脂腺中。由于其体积小且稳定，它很容易通过空气传播并附着在物体表面，对过敏的人造成持久的问题。方法本文综述了降低Fel d1表达和暴露、减轻其对人体过敏作用的创新策略。结果一个关键的方法是在饮食中添加针对Fel d1的鸡蛋源性IgY抗体。这些抗体中和唾液中的过敏原，显著减少其向皮毛和环境的转移，临床研究显示过敏个体的鼻症状显著减少。其他饮食因素，如ω -3脂肪酸、多酚和低血糖指数食物，可能通过激素和皮脂腺途径进一步调节过敏原的产生。免疫治疗方案包括针对猫的fell - cumv疫苗和针对人类的单克隆抗体（如REGN1908-1909）治疗，这两种方法都能显著减少过敏症状。基因改造和激素控制（例如，绝育）提供了进一步降低Fel d1表达的途径。环境策略，包括高效微粒过滤器和蛋白酶治疗，也可以帮助减少家庭中的过敏原负荷。总之，这些方法形成了一个管理猫过敏的多方面框架，潜在地允许过敏个体与他们的宠物共存。未来的研究应旨在优化这些干预措施，并探索协同组合，以实现更有效和个性化的过敏管理。本文综述了减少猫体内Fel d 1产生的创新方法，包括遗传、免疫和饮食方法，这些方法对预防人类过敏有潜在的指导意义。
{"title":"Innovative Strategies to Reduce Exposure and Expression of the Major Cat Allergen Fel d 1","authors":"Simone Colosimo, Cristiana Indolfi, Vittoria Frattolillo, Gianluca Mondillo, Alessandra Perrotta, Mariapia Masino, Fabio Decimo, Michele Miraglia del Giudice","doi":"10.1002/clt2.70098","DOIUrl":"https://doi.org/10.1002/clt2.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fel d 1, the primary allergen produced by cats, is a glycoprotein found mainly in their salivary and sebaceous glands. Due to its small size and stability, it easily becomes airborne and adheres to surfaces, posing a persistent problem for allergic individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This article reviews innovative strategies aimed at reducing Fel d 1 expression and exposure and mitigating its allergic effects on humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A key approach involves dietary supplementation with chicken egg-derived IgY antibodies specific to Fel d 1. These antibodies neutralize the allergen in the saliva, significantly reducing its transfer to the fur and environmental presence, with clinical studies showing a notable decrease in nasal symptoms among allergic individuals. Additional dietary factors, such as omega-3 fatty acids, polyphenols, and low-glycemic index foods, may further modulate allergen production via hormonal and sebaceous pathways. Immunotherapy options include the Fel-CuMV vaccine for cats and human-targeted treatments with monoclonal antibodies like REGN1908-1909, both of which demonstrate significant reductions in allergic symptoms. Genetic modification and hormonal manipulation (e.g., neutering) offer further avenues to lower Fel d 1 expression. Environmental strategies, including HEPA filters and protease treatments, can also help reduce allergen load in households.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, these approaches form a multifaceted framework for managing cat allergies, potentially allowing allergic individuals to coexist with their pets. Future research should aim to optimize these interventions and explore synergistic combinations to achieve more effective and personalized allergy management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Message</h3>\u0000 \u0000 <p>This review summarizes innovative methods for reducing Fel d 1 production in cats, including genetic, immunological and dietary approaches, with potential implications for allergy prevention in humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The efficacy of subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR) patients varies. Component-resolved diagnostics (CRD) may serve as a useful tool to predict therapeutic responses.
Methods
Forty-three house dust mite (HDM)-sensitized AR patients undergoing SCIT were enrolled. Clinical data and serum samples were collected at baseline (V1), 15 weeks (V2), and 1 year (V3). The levels of specific immunoglobulin E (sIgE) and sIgG4 to nine HDM components were measured, and a predictive model was established. An independent prospective cohort of 23 patients was used for validation.
Results
The most prevalent sensitizing components were Dermatophagoides pteronyssinus (Der p) 1, Dermatophagoides farinae (Der f) 1, Der p 2, Der f 2, and Der p 23. The responders had a significantly higher Combined Symptom and Medication Score (CSMS) at baseline than did the nonresponders. At V2, the responders showed a greater increase in serum levels of Der f 1 sIgE, higher levels of Der p 23 sIgG4, and greater incremental changes in Der p 23 sIgG4 levels. A composite model based on V1 CSMS, ∆15w Der f 1 sIgE, and ∆15w Der p 23 sIgG4 achieved an area under the receiver operating characteristic curve (AUC) of 0.896 (cutoff: 0.455), with 83.3% sensitivity and 84.0% specificity. In the validation cohort, the model showed a 75.0% positive predictive value, 86.7% negative predictive value, and 82.6% overall accuracy.
Conclusion
A composite biomarker model based on HDM component responses enabled early prediction of SCIT efficacy, supporting more personalized treatment strategies for AR management.
背景皮下免疫治疗（SCIT）对变应性鼻炎（AR）患者的疗效各不相同。成分解析诊断（CRD）可以作为预测治疗反应的有用工具。方法对43例屋尘螨（HDM）致敏AR患者行SCIT治疗。在基线（V1）、15周（V2）和1年（V3）收集临床资料和血清样本。测定9种HDM成分的特异性免疫球蛋白E （sIgE）和sIgG4水平，并建立预测模型。一项由23名患者组成的独立前瞻性队列研究用于验证。结果最常见的致敏成分为翼状螨（Der p） 1、粉状螨（Der f） 1、Der p2、Der f2和Der p23。应答者在基线时的综合症状和药物评分（CSMS）明显高于无应答者。在V2时，应答者血清中Der f1 sIgE水平升高，Der p23 sIgG4水平升高，Der p23 sIgG4水平增加。基于V1 csm、∆15w Der f 1 sIgE和∆15w Der p 23 sIgG4的复合模型的受试者工作特征曲线下面积（AUC）为0.896（截止值为0.455），敏感性为83.3%，特异性为84.0%。在验证队列中，该模型的阳性预测值为75.0%，阴性预测值为86.7%，总体准确率为82.6%。结论基于HDM成分反应的复合生物标志物模型可以早期预测SCIT疗效，为AR管理提供更个性化的治疗策略。
{"title":"Early Changes in House Dust Mite Component Specific Immunoglobulin Levels Predict the One-Year Efficacy of Allergen Immunotherapy in Patients With Allergic Rhinitis","authors":"Shuying Li, Yue Ma, Jiaying Li, Xian Feng, Fang Xiong, Miaomiao Han, Huabin Li, Hongfei Lou","doi":"10.1002/clt2.70099","DOIUrl":"https://doi.org/10.1002/clt2.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The efficacy of subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR) patients varies. Component-resolved diagnostics (CRD) may serve as a useful tool to predict therapeutic responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-three house dust mite (HDM)-sensitized AR patients undergoing SCIT were enrolled. Clinical data and serum samples were collected at baseline (V1), 15 weeks (V2), and 1 year (V3). The levels of specific immunoglobulin E (sIgE) and sIgG4 to nine HDM components were measured, and a predictive model was established. An independent prospective cohort of 23 patients was used for validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most prevalent sensitizing components were <i>Dermatophagoides pteronyssinus</i> (Der p) 1<i>, Dermatophagoides farinae</i> (Der f) 1, Der p 2, Der f 2, and Der p 23. The responders had a significantly higher Combined Symptom and Medication Score (CSMS) at baseline than did the nonresponders. At V2, the responders showed a greater increase in serum levels of Der f 1 sIgE, higher levels of Der p 23 sIgG4, and greater incremental changes in Der p 23 sIgG4 levels. A composite model based on V1 CSMS, ∆<sub>15w</sub> Der f 1 sIgE, and ∆<sub>15w</sub> Der p 23 sIgG4 achieved an area under the receiver operating characteristic curve (AUC) of 0.896 (cutoff: 0.455), with 83.3% sensitivity and 84.0% specificity. In the validation cohort, the model showed a 75.0% positive predictive value, 86.7% negative predictive value, and 82.6% overall accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A composite biomarker model based on HDM component responses enabled early prediction of SCIT efficacy, supporting more personalized treatment strategies for AR management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subcutaneous immunotherapy (SCIT) has been a cornerstone treatment for allergic rhinitis (AR) for over 50 years, consistently demonstrating symptom reduction and modulation of immune responses. Despite this, the underlying mechanisms responsible for the efficacy of SCIT remain incompletely understood, especially with regard to local immune responses in lymph nodes and nasal mucosa.
Aim
To determine the impact of SCIT treatment on immunoglobulin production in blood and nasal mucosa, as well as B cell class-switching in blood and lymph nodes.
Methodology
Blood, nasal lavage (NAL), and fine-needle aspirates (FNA) of inguinal lymph nodes were collected from 23 patients with birch and/or timothy pollen-induced AR before and after SCIT updosing. General response to SCIT was evaluated with symptom and medication scores, as well as allergen-mediated activation of basophils. Allergen-specific IgE, IgA, IgG, and IgG4 were measured in blood and NAL via ELISA. B-cell class-switching was assessed in blood and FNAs by flow cytometry.
Results
AR symptoms, medication use, and basophil sensitivity to allergens was reduced after SCIT updosing. Interestingly, the plasma levels of allergen-specific IgA, IgG, and IgG4 increased after SCIT updosing, while the levels of allergen-specific IgE and IgA decreased in NAL at this timepoint. Moreover, these results were accompanied by an increase in conventional (IgD−CD27+) and unconventional (IgD−CD27−) memory B cells in blood and lymph nodes, respectively.
Conclusion
This study highlights the differential effects of SCIT on local and systemic immunity and identifies early immunological changes associated with treatment. However, confirmation of long-term tolerance will require extended follow-up, including in-season analyses. The local decrease in allergen-specific IgA in NAL, alongside a systemic increase in allergen-specific IgA and IgG4, underscores the importance of assessing both mucosal and systemic responses when evaluating SCIT efficacy.
{"title":"Subcutaneous Allergen-Specific Immunotherapy for Allergic Rhinitis: Divergent IgA Responses in Nasal Mucosa and Blood With Validation of B Cell Class-Switching in Lymph Nodes and Blood","authors":"Maryam Jafari, Marianne Petro, Eirini Paziou, Eric Hjalmarsson, Agnetha Karlsson, Monika Ezerskyte, Laila Hellkvist, Susanna Kumlien Georén, Eduardo I. Cardenas, Lars-Olaf Cardell","doi":"10.1002/clt2.70097","DOIUrl":"https://doi.org/10.1002/clt2.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Subcutaneous immunotherapy (SCIT) has been a cornerstone treatment for allergic rhinitis (AR) for over 50 years, consistently demonstrating symptom reduction and modulation of immune responses. Despite this, the underlying mechanisms responsible for the efficacy of SCIT remain incompletely understood, especially with regard to local immune responses in lymph nodes and nasal mucosa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To determine the impact of SCIT treatment on immunoglobulin production in blood and nasal mucosa, as well as B cell class-switching in blood and lymph nodes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Blood, nasal lavage (NAL), and fine-needle aspirates (FNA) of inguinal lymph nodes were collected from 23 patients with birch and/or timothy pollen-induced AR before and after SCIT updosing. General response to SCIT was evaluated with symptom and medication scores, as well as allergen-mediated activation of basophils. Allergen-specific IgE, IgA, IgG, and IgG4 were measured in blood and NAL via ELISA. B-cell class-switching was assessed in blood and FNAs by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AR symptoms, medication use, and basophil sensitivity to allergens was reduced after SCIT updosing. Interestingly, the plasma levels of allergen-specific IgA, IgG, and IgG4 increased after SCIT updosing, while the levels of allergen-specific IgE and IgA decreased in NAL at this timepoint. Moreover, these results were accompanied by an increase in conventional (IgD<sup>−</sup>CD27<sup>+</sup>) and unconventional (IgD<sup>−</sup>CD27<sup>−</sup>) memory B cells in blood and lymph nodes, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the differential effects of SCIT on local and systemic immunity and identifies early immunological changes associated with treatment. However, confirmation of long-term tolerance will require extended follow-up, including in-season analyses. The local decrease in allergen-specific IgA in NAL, alongside a systemic increase in allergen-specific IgA and IgG4, underscores the importance of assessing both mucosal and systemic responses when evaluating SCIT efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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