Journal of Allergy and Clinical Immunology最新文献

{"title":"Transcriptome-wide association study of sex effects identifies sex-specific nasal epithelial gene expression profiles for total IgE","authors":"Molin Yue PhD ,&nbsp;Yidan Sun MS ,&nbsp;Yueh Ying Han PhD ,&nbsp;Glorisa Canino PhD ,&nbsp;Erick Forno MD, MPH, ATSF ,&nbsp;Judith M. Vonk PhD ,&nbsp;Elin T.G. Kersten MD, PhD ,&nbsp;Wei Chen PhD, ATSF ,&nbsp;Gerard H. Koppelman MD, PhD ,&nbsp;Juan C. Celedón MD, DrPH","doi":"10.1016/j.jaci.2025.12.1003","DOIUrl":"10.1016/j.jaci.2025.12.1003","url":null,"abstract":"<div><h3>Background</h3><div>Asthma is the most common chronic respiratory disease in children, with known sex differences in prevalence and severity that shift after puberty. Total IgE, a marker of type 2–high asthma, also differs by sex and age and may contribute to these disparities.</div></div><div><h3>Methods</h3><div>We tested whether nasal epithelial gene expression differs by sex and interacts with total IgE in ways that may inform asthma pathogenesis in a transcriptome-wide association study in nasal epithelial samples from participants in two cohorts: EVA-PR (including 398 Puerto Rican youths aged 12-20 years) and PIAMA (including 303 Dutch adolescents aged 16 years).</div></div><div><h3>Results</h3><div>Differential expression analysis by sex identified 406 genes at a false discovery rate–adjusted <em>P</em> value of &lt;.05, with 225 upregulated and 181 downregulated in female compared to male subjects. Top differentially expressed genes included hormone- and immune-related genes such as <em>THRB, IL17REL,</em> and <em>CD207</em>. Among these, 6 genes (<em>MNDA, IFIT1, IFIT2, SLC22A17, JAG2,</em> and <em>MT3</em>) showed significant sex-by-total IgE interaction effects on expression. Pathway enrichment analyses revealed that female subjects had activation of eukaryotic translation pathways (eg, <em>EIF2</em> signaling), while male subjects showed activation of immune-related pathways (eg, interferon signaling). Additionally, 19 pathways were enriched in the sex-by-IgE interaction model, including <em>TREM1</em> and cytokine storm signaling.</div></div><div><h3>Conclusions</h3><div>Our findings provide new insights into sex-specific regulation of gene expression in airway epithelium and its interaction with total IgE, helping to explain observed sex differences in asthma. This underscores the need to consider sex as a biological variable in asthma research and points to potential targets for precision medicine approaches.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1043-1051"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892374","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":"Inhibition of RIPK1 prevents keratinocyte cell death and reduces skin inflammation in type 1–mediated chronic inflammatory skin diseases","authors":"Manja Jargosch PhD ,&nbsp;Sophia Wasserer MD ,&nbsp;Jessica Eigemann ,&nbsp;Theresa Raunegger ,&nbsp;Nils Kurzen ,&nbsp;Danping Ding-Pfennigdorff PhD ,&nbsp;Eckart Bartnik PhD ,&nbsp;Carsten B. Schmidt-Weber PhD ,&nbsp;Tilo Biedermann MD ,&nbsp;Stefanie Eyerich PhD ,&nbsp;Kilian Eyerich MD, PhD ,&nbsp;Peter Florian PhD ,&nbsp;Matthias Herrmann PhD ,&nbsp;Joachim Saas PhD ,&nbsp;Felix Lauffer MD, PhD","doi":"10.1016/j.jaci.2026.02.006","DOIUrl":"10.1016/j.jaci.2026.02.006","url":null,"abstract":"<div><h3>Background</h3><div>Type 1–mediated chronic inflammatory skin diseases affect skin, hair, nails, and mucosa and dramatically impact patients’ quality of life. The 2 most prominent examples are lichen planus (LP) and cutaneous lupus erythematosus (CLE). Various cell death pathways are activated in both diseases, including apoptosis and necroptosis. RIPK1 is a key regulator of programmed cell death and thus represents a potential new target for treatment of these diseases.</div></div><div><h3>Objective</h3><div>We sought to determine the impact of RIPK1 on cell death and inflammation in LP and CLE.</div></div><div><h3>Methods</h3><div>RNA sequencing of inflammatory skin diseases (n = 179) assessed cell death, hypothermia, and inflammatory markers affected by eclitasertib, a novel RIPK1 inhibitor, in human cells, murine TNF-α-induced systemic inflammatory response syndrome model, reconstructed human epidermis, and <em>ex vivo</em> skin biopsy culture.</div></div><div><h3>Results</h3><div>Markers of apoptosis (<em>CASPASE8</em>) and necroptosis (<em>RIPK3</em>, <em>MLKL</em>) are upregulated in LP and CLE. Eclitasertib restored body temperature when orally administered 15 minutes after TNF-α injection in the murine systemic inflammatory response syndrome model. RIPK1 inhibition prevented keratinocyte cell death; normalized epidermal architecture; and decreased release of IL-1α, IL-1β, TNF-α, and CCL20 in reconstructed human epidermis on stimulation with LP and CLE T-cell supernatant. <em>Ex vivo</em> culture of LP and CLE biopsy specimens with eclitasertib reduced expression of disease-specific genes and downregulated pathways associated with inflammation.</div></div><div><h3>Conclusions</h3><div>Inhibition of RIPK1 targets 2 major pathogenic events in LP and CLE: epidermal cell death and type 1–mediated skin inflammation.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1087-1098"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226763","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":"Food and Drug Administration regulation of biosimilar products: Improving affordability of biologics for patients with asthma and allergic diseases","authors":"Sabiha Khan MD ,&nbsp;Thomas M. Herndon MD ,&nbsp;Anjeni Keswani MD, MSCI ,&nbsp;Katherine Clarridge MD, MSc ,&nbsp;Dipak S. Pisal MS, PhD ,&nbsp;Ping Ji PhD ,&nbsp;Jessica Kim PhD ,&nbsp;Martin Klein PhD ,&nbsp;Stacy Chin MD ,&nbsp;Chandrahas Sahajwalla PhD, FCP ,&nbsp;Kelly D. Stone MD, PhD","doi":"10.1016/j.jaci.2026.02.041","DOIUrl":"10.1016/j.jaci.2026.02.041","url":null,"abstract":"<div><div>On March 7, 2025, the US Food and Drug Administration (FDA) approved the first biosimilar to omalizumab (omalizumab-igec, Omlyclo; Celltrion). This is the first biosimilar approved for a biologic with an indication for the treatment of allergic diseases and/or asthma. Recent FDA announcements focus on accelerating biosimilar development and lowering costs by streamlining the approval process. On October 29, 2025, the FDA issued draft guidance proposing to no longer routinely require comparative clinical efficacy studies for biosimilarity, supporting the goal of reducing development time and cost. This review discusses FDA regulation of biologics and biosimilars, the recent approval of the first omalizumab biosimilar, and the evolving regulatory landscape for biosimilars to decrease the costs of their development while ensuring their efficacy and safety. The approval of biosimilars for treating allergic diseases and asthma is expected to significantly improve accessibility and affordability of these therapies, providing health care providers and patients with confidence in high-quality, cost-effective treatment options for patients with severe and refractory asthma and allergic conditions.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1009-1017"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439232","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":"Sex matters: IgE-associated nasal epithelial gene expression in asthma","authors":"Saptarshi Roy PhD,&nbsp;Pawan Sharma PhD","doi":"10.1016/j.jaci.2026.02.030","DOIUrl":"10.1016/j.jaci.2026.02.030","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1233-1234"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483671","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":"Exome sequencing reveals rare loss-of-function mutations in FLG and immune genes in patients with multiple food allergies","authors":"Anas M. Khanshour PhD ,&nbsp;Cynthia Haddad MD ,&nbsp;Steve Meregini MS ,&nbsp;Mellisa Zamudio BS ,&nbsp;Amy Arneson RN, BSN ,&nbsp;Christopher Parrish MD ,&nbsp;J. Andrew Bird MD ,&nbsp;Jeffrey A. SoRelle MD","doi":"10.1016/j.jaci.2026.01.001","DOIUrl":"10.1016/j.jaci.2026.01.001","url":null,"abstract":"<div><h3>Background</h3><div>Studies of twins, parents, and families have demonstrated a strong heritable role in allergy and food allergy in particular (60%-80%). However, genetic loci identified in previous genome-wide association studies focused on common variants, have not withstood validation, are not located inside protein coding exons, do not explain familial allergy, or have a low effect size.</div></div><div><h3>Objective</h3><div>We sought to apply forward genetics of families and exome sequencing to identify the frequency of Mendelian gene mutations for food allergy with emphasis on rare coding high-risk variants.</div></div><div><h3>Methods</h3><div>To enrich the probability of detecting Mendelian genetic variants, we included probands who had at least 2 food allergies confirmed by a food allergist. Family history of eczema, asthma, or food allergy was preferred but not required. Exome sequencing and analysis of DNA samples from probands, siblings, and parents was conducted to detect inheritance and enrichment of specific genes.</div></div><div><h3>Results</h3><div>Of 28 full trio families and 28 singletons, we found that 39.3% probands (n = 22/56) had a loss-of-function (LoF) mutation in <em>FLG</em>, a gene known to cause food allergy. We further found genes suspected of causing Mendelian food allergy: <em>SMAD3</em> LoF mutation (n = 1) and dominant inheritance of LoF mutations in <em>IFIH1</em> (MDA5) (n = 3 independent probands). <em>FLG</em> LoF mutations were significantly enriched in our non-Hispanic White cohort compared with 1100 non-Hispanic White controls (<em>P</em>_LoF = 4.28 × 10⁻⁴; odds ratio 3.38 [95% CI 1.72-6.67]). Notably, exome sequencing improved detection of <em>FLG</em> LoF mutations by 58% compared with previously used <em>FLG</em> genotyping methods, especially for people of non-European ancestry. Furthermore, we found <em>FLG</em> LoF variants in most subjects of African (55%, 5/9) ancestry with food allergy, but this observation could be limited by low sample size.</div></div><div><h3>Conclusions</h3><div>A Mendelian cause for food allergy may be present in 39.3% of patients with multiple food allergies. Expanded genomic studies of ethnically diverse groups and validation cohorts are warranted to uncover the variety of LoF variants from <em>FLG</em> present and confirm a potential role for MDA5.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1136-1146"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014522","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":"IRF1 is a master regulator of type 1 eosinophils","authors":"Immaculeta Osuji MS ,&nbsp;Nives Zimmermann MD","doi":"10.1016/j.jaci.2026.02.042","DOIUrl":"10.1016/j.jaci.2026.02.042","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1031-1033"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439558","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":"Disparities in asthma control and treatment: A spotlight on Mexican American children","authors":"Khamron Micheals PhD, MHA, RRT ,&nbsp;Emily M. Hall MPH ,&nbsp;Sarah Chambliss PhD, MSE ,&nbsp;Susan Balcer-Whaley MPH ,&nbsp;Rebecca A. Zárate PhD, MA ,&nbsp;Erin Rodriguez PhD, MS ,&nbsp;Roger Peng PhD ,&nbsp;Darlene Bhavnani PhD, MPH ,&nbsp;Elizabeth C. Matsui MD, MHS","doi":"10.1016/j.jaci.2025.10.032","DOIUrl":"10.1016/j.jaci.2025.10.032","url":null,"abstract":"<div><h3>Background</h3><div>Disparities in asthma morbidity between Black and non-Hispanic White children are well documented, but less is known about differences between Mexican American and non-Hispanic White children.</div></div><div><h3>Objective</h3><div>We sought to examine differences in asthma control and treatment between Mexican American and non-Hispanic White children with persistent asthma in Central Texas and contextualize these differences relative to those observed between Black and non-Hispanic White children.</div></div><div><h3>Methods</h3><div>Data were drawn from the Texas Home Assessment of Asthma and Lung Exposures study. Parents were surveyed about well-controlled asthma (defined as Asthma Control Test score ≥ 20), controller medication use in the past 2 weeks, socioeconomic status, and health care access. Logistic regression models were used to evaluate associations between race and ethnicity and asthma outcomes, with and without adjustment for socioeconomic and health care access factors.</div></div><div><h3>Results</h3><div>Among 202 children (46% Mexican American, 26% Black, 28% non-Hispanic White), Mexican American children had 81% lower odds of well-controlled asthma and 58% lower odds of controller medication use compared with non-Hispanic White children. These disparities persisted after adjusting for socioeconomic and health care access factors, though some associations were no longer statistically significant. Comparisons between Black and non-Hispanic White children demonstrated more pronounced disparities in asthma control and similar disparities in controller medication use.</div></div><div><h3>Conclusions</h3><div>Mexican American and Black children are less likely to have controlled asthma and use controller medications, reflecting persistent disparities not fully explained by socioeconomic and health care access factors.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1034-1042"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525214","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":"News beyond our pages","authors":"","doi":"10.1016/j.jaci.2026.03.009","DOIUrl":"10.1016/j.jaci.2026.03.009","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1024-1025"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147808029","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":"Effects of proton pump inhibitors on remodeling and fibrosis in eosinophilic esophagitis","authors":"Colby S. Sharlin MD ,&nbsp;Shingo Yamada MD, PhD ,&nbsp;Yuki Maekawa BS ,&nbsp;Kasumi Osonoi MD ,&nbsp;Kazuhiro Matsuyama BA ,&nbsp;Garrett A. Osswald BS ,&nbsp;Mark Rochman PhD ,&nbsp;Richard J. Taylor MD ,&nbsp;Mari Yamaguchi MD, PhD ,&nbsp;Yuichiro Tanaka MD, PhD ,&nbsp;Ting Wen MD, PhD ,&nbsp;Evan S. Dellon MD, MPH ,&nbsp;Marc E. Rothenberg MD, PhD ,&nbsp;Tetsuo Shoda MD, PhD","doi":"10.1016/j.jaci.2026.02.025","DOIUrl":"10.1016/j.jaci.2026.02.025","url":null,"abstract":"<div><h3>Background</h3><div>Eosinophilic esophagitis (EoE) is a progressive fibrostenotic disease. Although proton pump inhibitors (PPIs) are a first-line EoE treatment due to their anti-inflammatory effects, their effects on remodeling/fibrosis—likely driven in part by TGF-β—remain uncertain.</div></div><div><h3>Objectives</h3><div>To elucidate remodeling/fibrosis effects, this study evaluated whether PPIs impact the esophageal transcriptome of PPI-responsive EoE and counteract TGF-β‒induced fibrotic responses in human primary esophageal fibroblasts (HEFs).</div></div><div><h3>Methods</h3><div>Prospectively collected paired esophageal biopsies from patients with EoE pre‒/post‒PPI treatment were analyzed by RNA sequencing (RNA-seq). Histologic responsiveness to PPIs was defined as responders (&lt;15 eosinophils/high-power field, n = 10) or nonresponders (≥15 eosinophils/high-power field, n = 9). The ability of PPIs (esomeprazole, omeprazole) to attenuate <em>in vitro</em>, TGF-β‒mediated remodeling/fibrosis in HEFs was analyzed by quantitative PCR, RNA-seq, Western blotting, immunofluorescence, cell migration assays, and reactive oxygen species measurements.</div></div><div><h3>Results</h3><div>In PPI responders, we identified 746 differentially expressed genes pre‒/post‒PPI treatment (≥2-fold change, <em>P</em> &lt; .05), particularly those enriched in remodeling/fibrosis. In HEFs, TGF-β increased collagen I and α-smooth muscle actin expression via SMAD2/3 phosphorylation; however, PPIs attenuated these responses. RNA-seq revealed that PPIs reversed approximately 30% of TGF-β‒induced changes overlapping with fibrotic responses; 78 genes were concordantly modulated between patient biopsies and HEFs. Functional assays further confirmed that PPIs reduced TGF-β–induced collagen deposition, fibroblast motility, and reactive oxygen species production.</div></div><div><h3>Conclusions</h3><div>PPIs modulate remodeling-/fibrosis-related gene expression in patients with EoE and inhibit TGF-β‒induced profibrotic responses in HEFs, supporting antifibrotic potential that may help limit fibrostenotic progression in EoE.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages 1114-1126"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325956","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":"CME Calendar-AAAAI","authors":"","doi":"10.1016/S0091-6749(26)00231-9","DOIUrl":"10.1016/S0091-6749(26)00231-9","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"157 5","pages":"Pages A27-A28"},"PeriodicalIF":11.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807662","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}