Marc A Riedl,Jonathan A Bernstein,Joshua S Jacobs,Timothy Craig,William R Lumry,H James Wedner,Aleena Banerji,Selina Gierer,Andrew Smith,Michael E Manning,Francesca Perego,Laura Bordone,Sabrina Treadwell,Tao Lin,Kenneth B Newman,Aaron Yarlas,Danny M Cohn
BACKGROUNDDonidalorsen is an antisense oligonucleotide designed to reduce plasma prekallikrein in patients with hereditary angioedema (HAE). The Switch cohort of the OASISplus study (NCT05392114) evaluated the long-term safety and efficacy of donidalorsen in patients who switched from a long-term prophylactic treatment (LTP) to donidalorsen with 1-year outcomes.METHODSThis study enrolled patients with HAE aged ≥ 12 years previously on stable doses of an LTP (lanadelumab, berotralstat, C1 inhibitor). Patients directly switched from an LTP to donidalorsen 80 mg administered subcutaneously once every 4 weeks. Endpoints included incidence and severity of treatment-emergent adverse events (TEAEs; primary endpoint), monthly HAE attack rate, Angioedema Quality of Life (AE-QoL), and Angioedema Control Test (AECT) measured at baseline and Week 52.RESULTSSixty-five patients enrolled, and 54 (83.1%) completed 1 year. Eleven (16.9%) patients discontinued treatment during the first year, and one discontinued treatment after 1 year. Donidalorsen reduced HAE attack rates from baseline on the prior LTP by 67.6% over 52 weeks. Fifty-six of 64 (87.5%) dosed patients experienced a TEAE; most reported mild to moderate events. The most common treatment-related TEAEs were injection-site erythema (10.9%) and injection-site pruritus (10.9%). One patient had a serious adverse event that was not treatment-related. AE-QoL total score improved by 12.2 points (clinically meaningful ≥ 6 points) from baseline to Week 52, and 90.4% of patients had well-controlled disease (AECT ≥ 10) at Week 52.CONCLUSIONIn patients who switched from another LTP, donidalorsen was well tolerated and improved long-term HAE attack rates, quality of life, and disease control.
{"title":"Switching Long-Term Prophylaxis to Donidalorsen for Hereditary Angioedema: 1-Year OASISplus Results.","authors":"Marc A Riedl,Jonathan A Bernstein,Joshua S Jacobs,Timothy Craig,William R Lumry,H James Wedner,Aleena Banerji,Selina Gierer,Andrew Smith,Michael E Manning,Francesca Perego,Laura Bordone,Sabrina Treadwell,Tao Lin,Kenneth B Newman,Aaron Yarlas,Danny M Cohn","doi":"10.1111/all.70294","DOIUrl":"https://doi.org/10.1111/all.70294","url":null,"abstract":"BACKGROUNDDonidalorsen is an antisense oligonucleotide designed to reduce plasma prekallikrein in patients with hereditary angioedema (HAE). The Switch cohort of the OASISplus study (NCT05392114) evaluated the long-term safety and efficacy of donidalorsen in patients who switched from a long-term prophylactic treatment (LTP) to donidalorsen with 1-year outcomes.METHODSThis study enrolled patients with HAE aged ≥ 12 years previously on stable doses of an LTP (lanadelumab, berotralstat, C1 inhibitor). Patients directly switched from an LTP to donidalorsen 80 mg administered subcutaneously once every 4 weeks. Endpoints included incidence and severity of treatment-emergent adverse events (TEAEs; primary endpoint), monthly HAE attack rate, Angioedema Quality of Life (AE-QoL), and Angioedema Control Test (AECT) measured at baseline and Week 52.RESULTSSixty-five patients enrolled, and 54 (83.1%) completed 1 year. Eleven (16.9%) patients discontinued treatment during the first year, and one discontinued treatment after 1 year. Donidalorsen reduced HAE attack rates from baseline on the prior LTP by 67.6% over 52 weeks. Fifty-six of 64 (87.5%) dosed patients experienced a TEAE; most reported mild to moderate events. The most common treatment-related TEAEs were injection-site erythema (10.9%) and injection-site pruritus (10.9%). One patient had a serious adverse event that was not treatment-related. AE-QoL total score improved by 12.2 points (clinically meaningful ≥ 6 points) from baseline to Week 52, and 90.4% of patients had well-controlled disease (AECT ≥ 10) at Week 52.CONCLUSIONIn patients who switched from another LTP, donidalorsen was well tolerated and improved long-term HAE attack rates, quality of life, and disease control.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"29 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carmen Mochón-Jiménez,Jesús Gay-Mimbrera,Viviana Dávila-Flores,Helen He,Jerry Zhou,Irene Rivera-Ruiz,Pedro J Gómez-Arias,Juan de Luque-Fernández,Benjamin Ungar,Emma Guttman-Yassky,Juan Ruano
BACKGROUNDTape-strip RNA sequencing enables non-invasive molecular profiling of inflammatory skin diseases. However, its ability to capture immune activity, disease severity, and treatment response in alopecia areata (AA)-a follicle-centered autoimmune disorder-has not been systematically evaluated in relation to follicular immune activity and treatment response.OBJECTIVESTo determine whether scalp tape-strip RNA sequencing captures immune pathways associated with disease severity and treatment response in AA, and to assess its concordance with matched scalp biopsies.METHODSWe analyzed 61 RNA-seq profiles, including 46 scalp tape-strip samples (19 healthy controls, 17 active AA, and 10 post-baricitinib samples-five responders and five non-responders) and 15 lesional scalp biopsies. Nine tape-strip-biopsy pairs were obtained from the same scalp region. Batch-corrected expression data were analyzed using covariate-adjusted linear models and gene set-based enrichment analyses interrogating immune, cytotoxic, and follicular epithelial programs.RESULTSTape-strip RNA sequencing robustly recapitulated established AA-associated immune signatures, including activation of interferon/JAK-STAT signaling and cytotoxic T/NK cell pathways, together with suppression of follicular epithelial programs. Increasing disease severity was associated with progressive immune activation and epithelial loss. Baricitinib responders showed partial normalization of inflammatory signatures, whereas non-responders retained persistent immune activation, consistent with molecular non-response. Covariate-adjusted models identified treatment response-specific transcriptional changes. Tape-strip and biopsy transcriptomes demonstrated high concordance.CONCLUSIONSScalp tape-strip RNA sequencing captures clinically relevant immune and treatment-responsive molecular signatures in alopecia areata and represents a promising platform for longitudinal immune monitoring and biomarker-driven stratification of treatment response in follicle-centered autoimmune disease.
{"title":"Non-Invasive Scalp Tape-Strip RNA Sequencing Captures Disease Activity and Treatment-Response Signatures in Alopecia Areata.","authors":"Carmen Mochón-Jiménez,Jesús Gay-Mimbrera,Viviana Dávila-Flores,Helen He,Jerry Zhou,Irene Rivera-Ruiz,Pedro J Gómez-Arias,Juan de Luque-Fernández,Benjamin Ungar,Emma Guttman-Yassky,Juan Ruano","doi":"10.1111/all.70293","DOIUrl":"https://doi.org/10.1111/all.70293","url":null,"abstract":"BACKGROUNDTape-strip RNA sequencing enables non-invasive molecular profiling of inflammatory skin diseases. However, its ability to capture immune activity, disease severity, and treatment response in alopecia areata (AA)-a follicle-centered autoimmune disorder-has not been systematically evaluated in relation to follicular immune activity and treatment response.OBJECTIVESTo determine whether scalp tape-strip RNA sequencing captures immune pathways associated with disease severity and treatment response in AA, and to assess its concordance with matched scalp biopsies.METHODSWe analyzed 61 RNA-seq profiles, including 46 scalp tape-strip samples (19 healthy controls, 17 active AA, and 10 post-baricitinib samples-five responders and five non-responders) and 15 lesional scalp biopsies. Nine tape-strip-biopsy pairs were obtained from the same scalp region. Batch-corrected expression data were analyzed using covariate-adjusted linear models and gene set-based enrichment analyses interrogating immune, cytotoxic, and follicular epithelial programs.RESULTSTape-strip RNA sequencing robustly recapitulated established AA-associated immune signatures, including activation of interferon/JAK-STAT signaling and cytotoxic T/NK cell pathways, together with suppression of follicular epithelial programs. Increasing disease severity was associated with progressive immune activation and epithelial loss. Baricitinib responders showed partial normalization of inflammatory signatures, whereas non-responders retained persistent immune activation, consistent with molecular non-response. Covariate-adjusted models identified treatment response-specific transcriptional changes. Tape-strip and biopsy transcriptomes demonstrated high concordance.CONCLUSIONSScalp tape-strip RNA sequencing captures clinically relevant immune and treatment-responsive molecular signatures in alopecia areata and represents a promising platform for longitudinal immune monitoring and biomarker-driven stratification of treatment response in follicle-centered autoimmune disease.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"15 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anxiety, Depression, Schizophrenia, and Bipolar Disorder in Eosinophilic Esophagitis Patients: A Global Federated Cohort Analysis of Bidirectional Risks.","authors":"Hui-Chin Chang,Meng-Che Wu,Torsten Zuberbier,Shuo-Yan Gau","doi":"10.1111/all.70288","DOIUrl":"https://doi.org/10.1111/all.70288","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"198 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul Engeroff, Zahra Gharailoo, Monique Vogel, Martin F Bachmann
Immunoglobulin E (IgE) plays a central role in allergic diseases by binding to the high-affinity receptor FcεRI on mast cells and basophils, where allergen-induced crosslinking triggers potent inflammatory responses. Various mechanisms by which IgE responses are generated and functionally regulated remain elusive despite many years of research. Nevertheless, monoclonal anti-IgE therapy with omalizumab has transformed allergy treatment and proven to be safe and effective in various allergic indications. A remaining limitation of omalizumab is its high cost and requirement for repeated dosing, which limits accessibility. Vaccination against IgE theoretically offers a promising, cost-effective alternative, but long-standing safety concerns have slowed its development. Here, we review emerging concepts in IgE biology and therapeutic IgE neutralization. Recent research demonstrates that vaccine-induced anti-IgE antibodies can selectively neutralize free IgE while sparing FcεRI-bound IgE, thereby avoiding effector cell activation. This mechanism mirrors the behavior of natural anti-IgE autoantibodies, which may regulate physiological IgE homeostasis. Together, these novel insights indicate that anti-IgE vaccination is safe, biologically grounded, and a compelling strategy for the long-term control of IgE-mediated allergic disease.
{"title":"A Case for Anti-IgE Vaccination.","authors":"Paul Engeroff, Zahra Gharailoo, Monique Vogel, Martin F Bachmann","doi":"10.1111/all.70287","DOIUrl":"https://doi.org/10.1111/all.70287","url":null,"abstract":"<p><p>Immunoglobulin E (IgE) plays a central role in allergic diseases by binding to the high-affinity receptor FcεRI on mast cells and basophils, where allergen-induced crosslinking triggers potent inflammatory responses. Various mechanisms by which IgE responses are generated and functionally regulated remain elusive despite many years of research. Nevertheless, monoclonal anti-IgE therapy with omalizumab has transformed allergy treatment and proven to be safe and effective in various allergic indications. A remaining limitation of omalizumab is its high cost and requirement for repeated dosing, which limits accessibility. Vaccination against IgE theoretically offers a promising, cost-effective alternative, but long-standing safety concerns have slowed its development. Here, we review emerging concepts in IgE biology and therapeutic IgE neutralization. Recent research demonstrates that vaccine-induced anti-IgE antibodies can selectively neutralize free IgE while sparing FcεRI-bound IgE, thereby avoiding effector cell activation. This mechanism mirrors the behavior of natural anti-IgE autoantibodies, which may regulate physiological IgE homeostasis. Together, these novel insights indicate that anti-IgE vaccination is safe, biologically grounded, and a compelling strategy for the long-term control of IgE-mediated allergic disease.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hui Wen,Tessa Kole,Orestes A Carpaij,Tatiana Karp,Victor Guryev,Alen Faiz,Kian Fan Chung,Pankaj Bhavsar,Ian M Adcock,Salman Siddiqui,Andy Lan,Katie L Raby,Nazanin Zounemat-Kermani,Chris Brightling,Dave Singh,Janwillem Kocks,Monica Kraft,Bianca Beghé,Klaus F Rabe,Alberto Papi,Machteld N Hylkema,Martijn C Nawijn,Maarten van den Berge
BACKGROUNDTranscriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the "united airways" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways.METHODSIn the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427).RESULTSWe identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity.CONCLUSIONThe asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.
{"title":"Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways.","authors":"Hui Wen,Tessa Kole,Orestes A Carpaij,Tatiana Karp,Victor Guryev,Alen Faiz,Kian Fan Chung,Pankaj Bhavsar,Ian M Adcock,Salman Siddiqui,Andy Lan,Katie L Raby,Nazanin Zounemat-Kermani,Chris Brightling,Dave Singh,Janwillem Kocks,Monica Kraft,Bianca Beghé,Klaus F Rabe,Alberto Papi,Machteld N Hylkema,Martijn C Nawijn,Maarten van den Berge","doi":"10.1111/all.70283","DOIUrl":"https://doi.org/10.1111/all.70283","url":null,"abstract":"BACKGROUNDTranscriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the \"united airways\" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways.METHODSIn the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427).RESULTSWe identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity.CONCLUSIONThe asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"31 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Early-life co-exposure to O3 and PM2.5 amplifies childhood allergic rhinitis risk. PM2.5 and O3 jointly increased allergic rhinitis risk in preschool children, especially during infancy. Their synergistic effects appeared only above interaction thresholds and showed nonlinear exposure-response patterns, with stronger effects in eastern and central China.
{"title":"Interactive Effects of Ambient Fine Particulate Matter and Ozone on Childhood Allergic Rhinitis: China, Children, Homes, Health Study.","authors":"Tianyi Chen,Xinyi Fang,Qihong Deng,Xin Zhang,Ling Zhang,Wei Yu,Xiaohong Zheng,Tingting Wang,Hong Jiang,Xiaodan Yu,Zhuohui Zhao","doi":"10.1111/all.70285","DOIUrl":"https://doi.org/10.1111/all.70285","url":null,"abstract":"Early-life co-exposure to O3 and PM2.5 amplifies childhood allergic rhinitis risk. PM2.5 and O3 jointly increased allergic rhinitis risk in preschool children, especially during infancy. Their synergistic effects appeared only above interaction thresholds and showed nonlinear exposure-response patterns, with stronger effects in eastern and central China.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"16 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147374242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Associations of Chronic Rhinosinusitis and Nasal Polyps With Elevated Venous Thromboembolism Risk: Evidence From the UK Biobank.","authors":"Shenglong Xu,Zhaoman Wan,Xinlei Zhang,Peng Zhang,Luo Zhang,Yan Zhao","doi":"10.1111/all.70295","DOIUrl":"https://doi.org/10.1111/all.70295","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"69 3 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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