Journal of Allergy and Clinical Immunology最新文献

{"title":"MITF-associated metabolic signature in mast cells: A potential link to food anaphylaxis.","authors":"Laia Ollé, Mónica Barrios, Lihong Song, Sofia Carreras-Kàtcheff, Patricia Mir-Ihara, Laura Valls-Roca, Mariona Guitart-Mampel, Glòria Garrabou, Carmen García, Jose C Fernandez-Checa, Magda Babina, Rosa Muñoz-Cano, Margarita Martín","doi":"10.1016/j.jaci.2026.09.015","DOIUrl":"10.1016/j.jaci.2026.09.015","url":null,"abstract":"<p><strong>Background: </strong>Microphthalmia-associated transcription factor (MITF) is a master regulator of mast cell (MC) differentiation and effector function; it is essential for anaphylaxis (severe allergic reactions). Although MITF has been linked to mitochondrial regulation through pyruvate dehydrogenase, whether it broadly controls mitochondrial fitness and metabolic programs that exacerbate MC activation remains unclear.</p><p><strong>Objective: </strong>Our aim was to determine how MITF regulates MC mitochondrial function and metabolic fitness beyond pyruvate dehydrogenase control, as well as to define its contribution to heightened MC activation and food anaphylaxis.</p><p><strong>Methods: </strong>MITF was silenced, pharmacologically inhibited, or overexpressed in human MCs, followed by IgE- and MRGPRX2-dependent activation. Transcriptomic profiling and mitochondrial functional analyses were then performed. In parallel, MCs from patients with food anaphylaxis and from healthy controls were analyzed to assess clinical relevance.</p><p><strong>Results: </strong>Transcriptomic analysis of MITF-silenced MCs revealed a distinct metabolic signature characterized by downregulation of mitochondrial pathways and metabolic cellular compartments. MITF knockdown reduced mitochondrial fission, membrane potential, mitochondrial respiration, and mitochondrial marker expression of TOM20 and COX-IV, supporting a role for MITF in mitochondrial activity and metabolic regulation. Furthermore, compared with MCs from sensitized and healthy individuals, MCs from patients with food anaphylaxis exhibited increased MITF expression, elevated levels of mitochondrial markers, enhanced mitochondrial respiration, and a glycolytic shift after allergen activation,. Notably, pharmacologic inhibition of MITF reduced mitochondrial membrane potential in patient-derived MCs.</p><p><strong>Conclusions: </strong>MITF is a central regulator of MC mitochondrial function; it is associated with enhanced metabolic activity in anaphylaxis, highlighting MITF-driven pathways as potential therapeutic targets in MC-mediated allergic disease.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074375","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":"miRNA profiling identifies biomarkers and regulatory networks involving TGF-β/T-cell pathways in food protein-induced enterocolitis syndrome.","authors":"Alberto Gómez-Carballa, Julián Montoto-Louzao, Sandra Viz-Lasheras, Irene Rivero Calle, Jacobo Pardo-Seco, Xabier Bello, Nour El Zahraa Mallah, Adrián Álvarez-Martín, Laura Argiz, Robert J Boyle, Adnan Custovic, Jethro Herberg, Myrsini Kaforou, Stefania Arasi, Alessandro Fiocchi, Valentina Pecora, Simona Barni, Francesca Mori, Teresa Bracamonte, Luis Echeverria, Virginia O'Valle-Aísa, Noelia Lara Hernández-Martínez, Iria Carballeira, Emilio García, Carlos Garcia-Magan, José Domingo Moure-González, Purificación Gonzalez-Delgado, Teresa Garriga-Baraut, Sonsoles Infante, Gabriela Zambrano-Ibarra, Margarita Tomás-Pérez, Adrianna Machinena, Mariona Pascal, Ana Prieto, Sonia Vázquez-Cortes, Montserrat Fernández-Rivas, Leticia Vila, Laia Alsina, María José Torres, Giusi Mangone, Maria-Fernanda González-Matamala, Federico Martinón-Torres, Marta Vázquez-Ortiz, Antonio Salas","doi":"10.1016/j.jaci.2026.09.016","DOIUrl":"10.1016/j.jaci.2026.09.016","url":null,"abstract":"<p><strong>Background: </strong>Acute food protein-induced enterocolitis syndrome (FPIES) is a potentially life-threatening, non-IgE-mediated food allergy that primarily affects young children. Currently, diagnosis relies on clinical presentation and oral food challenges, which carry inherent risks. Consequently, FPIES is often misdiagnosed, leading to unnecessary interventions and delayed management. Despite its clinical relevance, the molecular mechanisms underlying FPIES remain poorly understood.</p><p><strong>Objective: </strong>We investigated the role of microRNAs (miRNAs) in FPIES and assessed their diagnostic potential.</p><p><strong>Methods: </strong>We analyzed miRNA expression profiles in peripheral blood from 29 children with oral food challenge-confirmed moderate to severe FPIES reactions, collected on the challenge day at baseline (TP1), reaction onset (TP2), and 4 hours after reaction onset (TP3). Using a hybrid ensemble feature selection approach, we compared these profiles to those of 26 children with acute gastroenteritis and sepsis to identify FPIES-specific miRNA signatures.</p><p><strong>Results: </strong>Longitudinal analysis revealed an early heterogeneous miRNA response that evolved into a more consistent profile in TP3, suggesting a dynamic and evolving regulatory response. Eleven miRNAs emerged as key regulators, highlighting pathways partially shared with other allergic and inflammatory conditions. In silico pathway analysis identified TGF-β signaling and T-cell differentiation as candidate pathways potentially involved in FPIES. Importantly, we discovered and validated 26 miRNAs signatures that accurately distinguish FPIES from sepsis and acute gastroenteritis, including a minimal 2-miRNA diagnostic signature (area under the curve = 0.98). miRNA-29a correlated with severe FPIES reactions, suggesting involvement in severity mechanisms.</p><p><strong>Conclusion: </strong>Our study reveals novel miRNA-mediated mechanisms in FPIES and identifies candidate biomarkers with diagnostic utility, paving the way for new molecular tools and therapeutic strategies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074396","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":"Corrigendum.","authors":"","doi":"10.1016/j.jaci.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038767","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":"Standardized Human Phenotype Ontology annotation enables high-quality phenotypic data capture in a real-world common variable immunodeficiency cohort.","authors":"Luiza C Campos, Émeline Favreau, Daniel Greene, Justyna Blach, Moira Thomas, Khuloud Alsehaim, Leman Mutlu, Sara Elhadari, Archana Herwadkar, Julia Payne, Charley Lever, Dina Mahmoud, Fernando Moreira, Mary O'Sullivan, Maxine Berry, George Twigg, Alice C J Hart, Nehal Joshi, Stewart Fuller, Kenneth G C Smith, Ernest Turro, Matthew C Cook, Chris Wallace, Siobhan O Burns","doi":"10.1016/j.jaci.2026.08.027","DOIUrl":"10.1016/j.jaci.2026.08.027","url":null,"abstract":"<p><strong>Background: </strong>Patients with common variable immunodeficiency (CVID) exhibit diverse clinical manifestations, indicating heterogeneity in pathogenic mechanisms. Systematic application of standardized phenotyping in large cohorts is essential to dissect this heterogeneity. The Human Phenotype Ontology (HPO) provides a structured framework for capturing and comparing disease phenotypes.</p><p><strong>Objective: </strong>We evaluated the application of systematic HPO-based phenotyping in CVID patients enrolled for whole-genome sequencing in a large national adult primary immunodeficiency cohort.</p><p><strong>Methods: </strong>We developed a web-based Phenotype Capture Tool and delivered structured clinician training to standardize HPO annotation. Numerical laboratory parameters were mapped to corresponding HPO terms to enrich patient records.</p><p><strong>Results: </strong>We coded the phenotypes of 526 CVID patients across 11 centers in the United Kingdom. Clinician training increased phenotype granularity and improved phenotyping consistency between clinicians. We assigned 883 unique HPO terms across the cohort and applied logical rules to the terms to classify cases into an infection-only group and a complex phenotype group (42% vs 58%, respectively). Patients in the complex phenotype group were significantly more likely to have reduced switched memory and expanded CD21^low B cells, as well as pathogenic variants in International Union of Immunological Societies-listed genes overall and pathogenic NFKB1 variants specifically. Having a pathogenic variant in a listed gene was associated with Autoimmune hemolytic anemia [HP:0001890] and having a pathogenic NFKB1 variant specifically was associated with Autoimmune neutropenia [HP:0001904].</p><p><strong>Conclusion: </strong>This is the first study to systematically collect granular HPO-coded phenotypes in a large real-world CVID cohort, refining the CVID landscape and providing a comprehensive CVID HPO term set relevant for international research.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017011","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":"Mechanistic and clinical updates in chronic rhinosinusitis: 2023 to 2025.","authors":"Sajel T Peters, Atsushi Kato, Whitney W Stevens","doi":"10.1016/j.jaci.2026.08.028","DOIUrl":"10.1016/j.jaci.2026.08.028","url":null,"abstract":"<p><p>Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nose and paranasal sinuses associated with poor quality of life and high health care burden. CRS is broadly classified into 2 subtypes on the basis of whether nasal polyps are present (CRSwNP) or absent (CRSsNP). Although CRSsNP is more prevalent, the underlying mechanisms contributing to CRSwNP pathogenesis have been more extensively defined over the years. CRSwNP is characterized by type 2 inflammation as well as epithelial barrier dysfunction, and in the past 3 years, a new endotype has been defined, inflammatory cell heterogeneity has been identified, novel cell populations have been discovered, and mechanisms contributing to epithelial barrier dysfunction have been advanced. Clinically, 4 biologics targeting type 2 inflammation are now FDA-approved for CRSwNP. As these therapies become increasingly common in clinical practice, ongoing investigations have focused on comparing their efficacy and defining their role alongside more established interventions such as corticosteroids and sinus surgery. In this review, novel mechanistic findings and recent clinical developments in CRS between 2023 and 2025 have been highlighted.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016970","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":"Developments in Mast Cell Research.","authors":"Adrian M Piliponsky, Teal S Hallstrand","doi":"10.1016/j.jaci.2026.09.008","DOIUrl":"10.1016/j.jaci.2026.09.008","url":null,"abstract":"<p><p>This review summarizes major advances in mast cell (MC) research published between January 2024 and December 2025. Recent discoveries have reshaped our understanding of MC biology, revealing previously unrecognized roles in brain development, mucosal immunity, neuroimmune communication, and cancer. High-resolution structural studies have provided new insights into high affinity receptor for immunoglobulin (Ig)E (FcεRI) signaling, while emerging evidence has expanded the functional repertoire of inflammasome components and established Mas-related G-protein coupled receptor member (MRGPRX)2 as a central receptor mediating IgE-independent MC activation. Single-cell transcriptomic and spatial profiling studies have uncovered remarkable MC heterogeneity, identifying specialized populations with distinct homeostatic and pathogenic functions across tissues. These findings have also redefined the contribution of MCs to early-life allergic disease, anaphylaxis, pain, infection, and tumor immunity, highlighting their context-dependent functions. In parallel, major therapeutic advances-including antibodies targeting the KIT-stem cell factor (SCF) axis, next-generation anti-IgE therapies, Bruton's tyrosine kinase (BTK) inhibitors, and strategies targeting type 2 inflammatory pathways-are accelerating the development of more selective treatments for MC-driven disorders. Advances in experimental platforms, including human skin MC cultures, receptor-humanized and humanized mouse models, and computational pathology, are further expanding the tools available to investigate MC biology and accelerate translational research. Together, these conceptual, technological, and therapeutic advances are shaping the next generation of MC-targeted therapies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nasal epithelial transcriptome-wide isoform-level expression and asthma endotypes in youth.","authors":"Tianhao Liu, Molin Yue, Kristina Gaietto, Haoran Hu, Xiangyu Ye, Franziska J Rosser, Yueh-Ying Han, Wei Chen, Juan C Celedón","doi":"10.1016/j.jaci.2026.09.005","DOIUrl":"10.1016/j.jaci.2026.09.005","url":null,"abstract":"<p><strong>Background: </strong>Previous transcriptome-wide association studies of asthma lacked analyses of isoform expression.</p><p><strong>Objective: </strong>We sought to identify isoforms associated with asthma endotypes in children and adolescents.</p><p><strong>Methods: </strong>Meta-analysis of association between isoform- and gene-level nasal epithelial expression and T_H2-high or T_H17-high asthma (with T_H2-low/T_H17-low asthma as the reference group) in 459 youths with asthma aged 8-20 years in 3 studies: Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR), Stress and Treatment Response in Puerto Rican and African American Children With Asthma (STAR), and Vitamin D Kids Asthma (VDKA). Genes or isoforms with the same direction of association with an endotype in all cohorts and a meta-analysis false discovery rate-adjusted P < .01 were considered to have significantly differential expression.</p><p><strong>Results: </strong>In total, 6,607 isoforms encoded by 5,168 genes were associated with T_H2-high asthma; 1,019 (19.7%) of these 5,168 genes were only identified in the isoform analysis, including CTNND1, CREM, TAOK2, and AIM1. A total of 4,430 isoforms encoded by 3,643 genes were associated with T_H17-high asthma; 371 (10.2%) of these genes were only identified in the isoform analysis, including PSAP, FAM65B, and CFLAR. While top findings in the gene- and isoform-level analyses often overlapped, the isoforms of many genes showed differential isoform usage. In T_H2-high asthma, 499 genes (encoding 731 isoforms) altered isoform usage, including CDH26, IL1RL1, MAP2K6, and SLC39A8. In T_H17-high asthma, 113 genes (encoding 160 isoforms) altered isoform usage, including SBNO2, PSMB8, and NCOA7.</p><p><strong>Conclusions: </strong>An isoform-level analysis complemented a gene-level analysis of expression and identified novel genes for asthma endotypes.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012317","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":"ABACHAI phase 2 clinical trial: Safety and efficacy of subcutaneous abatacept in patients with CTLA-4 insufficiency or LRBA deficiency.","authors":"Máté Krausz, Georgios Sogkas, Annette Uhlmann, Gabriele Ihorst, Sigune Goldacker, Torsten Witte, Manuel Feißt, Laia Alsina, Ingunn Dybedal, Mike Recher, Klaus Warnatz, Bodo Grimbacher","doi":"10.1016/j.jaci.2026.09.007","DOIUrl":"10.1016/j.jaci.2026.09.007","url":null,"abstract":"<p><strong>Background: </strong>Heterozygous germline mutations in CTLA4 (CTLA-4 insufficiency) and biallelic mutations in LRBA (lipopolysaccharide-responsive beige-like anchor protein [LRBA] deficiency) cause immune dysregulation with autoimmunity, lymphoproliferation, and immunodeficiency. For treatment, abatacept has been used successfully and is increasingly being used off-label; however, prospective clinical trial data are missing.</p><p><strong>Objective: </strong>We evaluated the safety and efficacy of abatacept in patients with CTLA-4 insufficiency or LRBA deficiency.</p><p><strong>Methods: </strong>ABACHAI was a prospective, open-label, single-arm phase 2a trial. Adult patients with genetically confirmed CTLA-4 insufficiency or LRBA deficiency and at least one clinically significant organ manifestation received 125 mg abatacept subcutaneously once a week for 12 months. The primary end point was safety, defined as the number of episodes of failed infection control. Secondary end points included additional safety parameters, efficacy outcomes, and patient-reported quality of life.</p><p><strong>Results: </strong>Twenty patients were enrolled (18 with CTLA-4 insufficiency and 2 with LRBA deficiency). Three patients had 5 severe infections during treatment (incidence rate, 0.27 per patient-year), comparable to the year before enrollment. No Epstein-Barr virus or cytomegalovirus reactivations occurred. Abatacept reduced lymphoproliferation and immune activation and improved patient-reported quality of life and gastrointestinal symptom quality. Cytopenias and renal involvement were not sufficiently controlled. Four patients (20%) discontinued therapy, 3 because of unrelated serious adverse events and 1 because of noncompliance.</p><p><strong>Conclusion: </strong>ABACHAI was the first prospective interventional trial examining abatacept treatment in CTLA-4 insufficiency and LRBA deficiency. Abatacept demonstrated a favorable safety profile and organ-specific efficacy, with strongest responses in lymphoproliferation and immune activation. Patients with refractory cytopenias or progressive organ involvement may require additional or alternative therapeutic strategies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008649","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":"Age-stratified CD19⁺ B-cell reference values in children and adolescents-a systematic review and meta-analysis.","authors":"Diana Ljung Sass, Alessandro Camponeschi, Magnus Pettersson, Karin Mellgren","doi":"10.1016/j.jaci.2026.07.027","DOIUrl":"10.1016/j.jaci.2026.07.027","url":null,"abstract":"<p><strong>Background: </strong>Accurate monitoring of B-cell reconstitution is dependent on age-specific pediatric reference ranges. However, pediatric CD19⁺ B-cell reference values currently lack harmonization and are inconsistently defined.</p><p><strong>Objective: </strong>We sought to systematically evaluate published pediatric reference values for CD19⁺ B cells in healthy children and adolescents (age range, 0-18 years).</p><p><strong>Methods: </strong>This review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines. A comprehensive literature search was performed for studies reporting CD19⁺ B cells in healthy children from 2000 to 2025 (final search in March 2025). Records were independently screened and assessed for quality by 3 investigators. Data for lower limit of normal (lower limit of 95% reference interval) were analyzed and compared for different age groups.</p><p><strong>Results: </strong>After screening, 29 publications met the inclusion criteria, representing a total cohort of 10,399 individuals. Our analysis showed that the lower limit of normal of CD19⁺ B-cell values differed according to the age of the child. We identified 5 distinct age groups and corresponding values of lower limit of normal. In children younger than 6 years, B-cell values were consistently different from values that have been reported for adults.</p><p><strong>Conclusion: </strong>This systematic synthesis summarizes consolidated age-stratified lower limits of normal values for CD19⁺ B cells in children and adolescents. Proposed CD19⁺ B-cell values can be used for standardized clinical monitoring of B-cell recovery to normal values after CD19-depleting therapy.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001950","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":"Exploiting KREC: Time for newborn screening and beyond-proceedings from the First International KREC Consortium Meeting.","authors":"Paola R Suhet, Jordan Abbott, Roshini S Abraham, Mei W Baker, Oksana Boyarchuk, Karlla W Brigatti, Manish J Butte, Christopher Chang, Hey Chong, Antonio Condino-Neto, Zsuzsanna Gaál, Mariana P Gouveia-Pereira, Eyal Grunebaum, Stella Hartono, Hirokazu Kanegane, Anne Pham-Huy, Edgar Borges de Oliveira-Junior, Revathi Raj, Christine M Seroogy, Pere Soler-Palacin, Raz Somech, Vanessa Tenembaum, Mirjam van der Burg, Jolan E Walter","doi":"10.1016/j.jaci.2026.09.003","DOIUrl":"10.1016/j.jaci.2026.09.003","url":null,"abstract":"<p><p>Newborn screening (NBS) for severe combined immunodeficiency using T-cell receptor excision circles has changed the diagnosis and outcomes for infants with profound T-cell lymphopenia. However, patients with severe B-cell lymphopenia are still typically diagnosed only after serious or recurrent infections or irreversible complications. Some countries now measure kappa-deleting recombination excision circles (KREC) together with T-cell receptor excision circles to identify infants with severe B-cell lymphopenia, but adoption remains limited. The First International KREC Consortium Meeting, held in Tampa, Florida, in February 2026, convened clinicians, laboratory scientists, public health experts, patient advocates, and families from North America, Europe, Asia, and South America to review current experience and implementation strategies for broader KREC screening. Sessions covered international screening programs, laboratory methods, assay harmonization, interpretation and reporting, clinical impact of early diagnosis, therapeutic options, and policy pathways for implementation. Patients and families shared personal experiences of delayed diagnosis and perspectives on NBS. The meeting identified key priorities for future implementation, including the justification of this assay on the basis of impact in patient care and feasibility for integration into current NBS approaches on the basis of health-economic evaluation. Once implemented, next steps include harmonization of methods and reporting, strategies to minimize false-positive results and referrals, and follow-up pathways. These proceedings summarize the major discussions and outline priorities for collaborative evidence generation and future implementation.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990159","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}