Journal of Allergy and Clinical Immunology最新文献

{"title":"Biomarkers of Inflammation Associated with Radon Exposure in the School Inner-City Asthma Study (SICAS).","authors":"Tina M Banzon, Youn Soo Jung, Kimberly F Greco, Longxiang Li, Kari Nadeau, Perdita Permaul, Petros Koutrakis, Jonathan M Gaffin, Wanda Phipatanakul","doi":"10.1016/j.jaci.2025.01.033","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.033","url":null,"abstract":"<p><strong>Background: </strong>Radon is an omnipresent radioactive gas recently reported to be associated with increased asthma morbidity.</p><p><strong>Objective: </strong>We aimed to identify biomarkers associated with radon exposure and hypothesized elevated radon exposure to be associated with increased inflammatory biomarker levels in an exploratory analysis.</p><p><strong>Methods: </strong>In 137 schoolchildren with asthma in the School Inner-City Asthma Study, we assessed estimated radon exposure (1-month averaged radon) by a spatiotemporal model and 46 inflammatory biomarker outcomes, adjusting for co-pollutants (PM_2.5, NO₂, O₃) and performed mixed effect regression analysis. Causal mediation analysis was used to determine the association between radon exposure and absolute eosinophil count.</p><p><strong>Results: </strong>In a total of 137 observations, we found a positive association with radon exposure and interleukin-5 (IL-5), a TH₂ cytokine known to recruit eosinophils to asthmatic airways. Higher radon was significantly associated with a greater increase in IL-5 compared to low radon exposure (obs=137; 1-month moving radon average [RR=1.134, 95% CI 1.004 - 1.280; p=0.044]). Mediation analysis revealed an indirect effect of IL-5 (β=0.006, 95% CI 0.001 - 0.012; p=0.024) on the association between radon exposure and absolute eosinophil count. This suggests the effect of radon on eosinophil count is mediated through IL-5.</p><p><strong>Conclusions: </strong>Radon is a potential novel, modifiable risk factor for asthma recently reported to be associated with asthma morbidity. This work identifies important biological disease pathways via biomarkers that may be central to the exposure-outcome relationship.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382583","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":"Efficacy and safety of GR1802 in uncontrolled CRSwNP: placebo-controlled phase 2 trial.","authors":"Ming Zheng, Di Wu, Yingshi Piao, Jun Tang, Fang Quan, Bing Guan, Hongmeng Yu, Xiaowen Zhang, Gang He, Yucheng Yang, Lijia Wan, Xuezhong Li, Wen Liu, Zhendong Xu, Jing Ye, Wen Liu, Xicheng Song, Yuxiao Du, Yu Xu, Jianjun Chen, Wei Wang, Feng Lan, Chengshuo Wang, Luo Zhang","doi":"10.1016/j.jaci.2025.01.034","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.034","url":null,"abstract":"<p><strong>Background: </strong>Anti-interleukin-4 receptor subunit alpha (IL-4Rα) treatments can effectively treat eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). However, their impact on the overall population of uncontrolled CRSwNP remains unclear.</p><p><strong>Objectives: </strong>To evaluate the safety and efficacy of GR1802, a novel anti-IL-4Rα monoclonal antibody, in uncontrolled CRSwNP patients.</p><p><strong>Methods: </strong>Seventy uncontrolled CRSwNP participants were randomized (1:1) to receive either GR1802 (300 mg with an initial doubled dose) or placebo every 2 weeks. Primary endpoints were the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Secondary endpoints mainly included change from baseline in total nasal symptom score (TNSS), 22-item Sino-Nasal Outcome Test (SNOT-22) score, and Lund-Mackay score. Efficacy (exploratory) was also analyzed in ECRSwNP and NECRSwNP subgroups. Safety was evaluated throughout the study.</p><p><strong>Results: </strong>In uncontrolled CRSwNP participants, GR1802 significantly improved NPS and NCS when compared to placebo, with least squares (LS) mean differences of -2·1 (95% confidence interval [CI] [-2·6, -1·5]) and -0·8 (95% CI [-1·1, -0·4]) respectively. Participants treated with GR1802 had significantly decreased TNSS, SNOT-22 score, and Lund-Mackay score. The subgroup analysis demonstrated that GR1802 improved the symptoms and life quality both in ECRSwNP and NECRSwNP participants, as evidenced by changes in NPS, University of Pennsylvania Smell Identification Test (UPSIT) score, and Lund-Mackay score. Treatment-related adverse events occurred in 19·4 % of the GR1802 group and 17·6 % of the placebo group.</p><p><strong>Conclusion: </strong>GR1802 is well-tolerated and effective in treating the overall population with uncontrolled CRSwNP.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382593","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":"Deficiency of adenosine deaminase 2 skews adaptive immune repertoires towards specific sets of T and B cell receptors.","authors":"Christoph Schultheiß, Paul Schmidt-Barbo, Lisa Paschold, Carl Esperanzate, Alissa Behn, Rafael Mikolajczyk, Daniel L Kastner, Ivona Aksentijevich, Mascha Binder","doi":"10.1016/j.jaci.2025.01.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.032","url":null,"abstract":"<p><strong>Background: </strong>Adenosine deaminase 2 deficiency (DADA2) is a genetic disorder caused by biallelic hypomorphic or loss-of-function mutations in the ADA2 gene that encodes a protein deaminase regulating extracellular adenosine metabolism. Clinical features encompass inflammatory vasculopathy, early-onset strokes, and a complex presentation involving both immunodeficiency and autoinflammation/autoimmunity.</p><p><strong>Objective: </strong>To determine a DADA2-specific adaptive immune architecture.</p><p><strong>Methods: </strong>We profiled immunoglobulin levels and peripheral B and T cell phenotypes in 47 previously reported and 5 unreported DADA2 patients. Levels of 21 cytokines/chemokines were quantified in patients with or without anti-TNF treatment. To characterize the DADA2 immune architecture, we performed T and B cell receptor (TCR/BCR) immunosequencing. We trained a binary LightGBM classifier to distinguish DADA2 T and B cell immune repertoires from heathy individuals.</p><p><strong>Results: </strong>We detected hypogammaglobulinemia in 65% of DADA2 patients (34/52) and cytopenias in 48% (25/52). Flow cytometric profiling revealed contraction of B and T cell memory compartments. In addition, we observed elevated levels of TNF, IL-8, several interferons, APRIL, BAFF and sCD40L. High serum levels of TNF, BAFF and sCD40L persisted under anti-TNF therapy. Next-generation immunosequencing of peripheral lymphocytes showed restricted TCR repertoires and B cells, which were particularly skewed towards IGHV4-34 rearrangements. Our machine learning algorithm separated DADA2 with high accuracy from healthy individuals based on immunogenetic parameters regarding B cell clone fraction, CDR3 length, and selected Kidera factors.</p><p><strong>Conclusions: </strong>Our findings underscore ADA2's significant influence on the adaptive immune system, which results in a highly specific immunogenetic signature in DADA2 patients.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382590","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":"Uncovering new players in IL-5 signaling: Mast cells, mast cell progenitors, and beyond.","authors":"Tanya M Laidlaw","doi":"10.1016/j.jaci.2025.01.037","DOIUrl":"10.1016/j.jaci.2025.01.037","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382016","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":"Loss of Bach2 in T cells causes prolonged allergic inflammation through the accumulation of effector T cells and disruption of the epidermal barrier.","authors":"Miyuki Omori-Miyake, Ryosuke Kawakami, Makoto Kuwahara, Masataka Okabe, Jun Muto, Takeshi Imamura, Masakatsu Yamashita","doi":"10.1016/j.jaci.2025.01.036","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.036","url":null,"abstract":"<p><strong>Background: </strong>Bach2 has been suggested to be a risk factor for allergic diseases in previous studies. Since type IV hypersensitivity reactions, including allergic contact dermatitis (ACD), develop through activated T cells and because the expression of Bach2 is regulated in the development and functional differentiation of T cells, the expression of Bach2 in T cells may be involved in the onset of ACD. However, the role of Bach2 in T cells during ACD development has not yet been determined.</p><p><strong>Objective: </strong>We investigated the role of the appropriate expression of Bach2 in T cells in the development and prolongation of ACD.</p><p><strong>Methods: </strong>We induced ACD in mice by repeatedly applying a hapten and analyzed the expression of Bach2 in the T cells of lesional skin or skin-draining lymph nodes (sdLNs). We performed a phenotypic analysis of the skin and/or sdLNs by comparing mice with T cells overexpressing Bach2 or with Bach2 loss to the control mice.</p><p><strong>Results: </strong>We found that Bach2^lo T cells accumulated in the skin and sdLNs as ACD developed. T cell-specific Bach2 deficient mice showed more severe inflammatory responses to the hapten and had prolonged inflammation with T cells expressing higher levels of IL-13 in the skin and IFN-γ and IL-13 in the sdLNs. In contrast, the mice overexpressing Bach2 in T cells developed almost no symptom of ACD.</p><p><strong>Conclusion: </strong>The appropriate expression of Bach2 in T cells may be a key factor in the resolution of ACD.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382600","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":"Real-life observation of wildfire-smoke impaired COVID-19 vaccine immunity.","authors":"Gursharan Kaur Sanghar, Melissa Teuber, Resmi Ravindran, Emma Jean Keller, Sean Raffuse, Pedro Hernandez, Angela Linderholm, Gabrielle Echt, Lisa Franzi, Kaelyn Tuermer-Lee, Maya Juarez, Timothy Albertson, Imran Khan, Angela Haczku","doi":"10.1016/j.jaci.2025.01.035","DOIUrl":"10.1016/j.jaci.2025.01.035","url":null,"abstract":"<p><strong>Background: </strong>Wildfires are increasingly common with wildfire smoke affecting millions globally, yet its impact on immune responses is poorly understood.</p><p><strong>Objective: </strong>This real-world study, conducted on participants in the Pfizer BNT162b2 COVID-19 vaccine trial, studied the effects of wildfire smoke exposure on long-term vaccine immunity.</p><p><strong>Methods: </strong>We recruited 52 healthy, non-smoking individuals (ages 26-83) who were either vaccinated (Group 1, n=28) or placebo injected (Group 2, n=24) during heavy wildfire smoke conditions. Group 2 subjects received vaccination several months later, outside of wildfire season. Blood was taken before and 1 month after vaccine or placebo injections, and 6 months after vaccination. We analyzed intracellular cytokines, B and NK cell markers by flow cytometry, and serum immunoglobulin levels against common coronaviruses using multiplex assays.</p><p><strong>Results: </strong>A robust spike receptor-binding domain (S-RBD)-specific IgG response observed 1 month post booster, declined variably 6 months later. Wildfire smoke acutely increased IL-13 expression by CD56^bright NK cells at the time of vaccination, that negatively correlated with anti-S-RBD IgG (r=-0.41, p<0.05). Total IgG levels positively correlated with the air quality index (AQI) measured during vaccination (r=0.96, p<0.01). Similarly to age (but not sex, BMI or race/ethnicity), the two-week AQI averages during vaccination showed a significant negative correlation with anti-S-RBD IgG levels 6 months later (r=-0.41, p<0.05).</p><p><strong>Conclusion: </strong>Wildfire smoke may lead to inappropriate immunoglobulin production and diminished vaccine immunity. We highlight a previously unrecognized pathway involving NK-cell derived IL-13 and non-specific B-cell activation and underscore the significance of environmental exposures in shaping immunity.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381255","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":"ICOSL, OX40L, and CD30L Control Persistence of Asthmatic CD4 Trm cells.","authors":"Gurupreet S Sethi, Ashmitaa Logandha Ramamoorthy Premlal, Ashu Chawla, Michael Croft","doi":"10.1016/j.jaci.2024.12.1097","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1097","url":null,"abstract":"<p><strong>Background: </strong>Tissue-resident memory CD4 T cells (Trm) are linked to asthma exacerbations and being able to reduce their frequency or activity has implications for clinical therapy.</p><p><strong>Objective: </strong>To find costimulatory molecules that control the reactivation of allergen-induced memory CD4 T cells and determine if their targeting alters the longevity of lung localizing memory T cell populations associated with asthma.</p><p><strong>Methods: </strong>Transcriptomic profiles of human and mouse asthmatic lung CD4 T cells were studied to identify potentially active costimulatory molecules, and the effect of blocking these molecules was examined in a model of disease exacerbation.</p><p><strong>Results: </strong>ScRNA-seq of allergen-responding lung CD4 T cells from asthma patients revealed expression of the costimulatory molecules ICOS, TNFRSF4 (OX40), and TNFSF8 (CD30L). In a murine model of allergic asthma exacerbations, scRNA-seq similarly demonstrated expression of Icos, Tnfrsf4, and Tnfsf8 in responding memory effector CD4 T cells even though many inflammatory subpopulations were induced in the lungs. Therapeutically inhibiting OX40L with CD30L in vivo partially suppressed the recall exacerbation response to allergen, but neutralizing ICOSL with OX40L or CD30L efficiently limited the accumulation of lung-localized memory effector T cells and ablated all aspects of lung inflammation. Importantly, transient therapeutic inhibition of these molecules together resulted in greatly reduced numbers and activity of tissue-resident memory CD4 T cells maintained in the lungs over time, even when mice were further challenged repeatedly with allergen. This led to a state of hyporesponsiveness such that subsequent exposure to allergen failed to re-exacerbate asthmatic lung tissue inflammation.</p><p><strong>Conclusion: </strong>Combined inhibition of ICOSL with OX40L or CD30L limits the continued accumulation of large populations of inflammatory lung tissue-resident memory CD4 T cells, revealing therapeutic treatments applicable for asthma.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373935","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":"Sputum short-chain fatty acids, microbiome, inflammation, and mucus plugging in obstructive airway disease.","authors":"Naoya Tanabe, Hisako Matsumoto, Chie Morimoto, Toyohiro Hirai","doi":"10.1016/j.jaci.2025.01.031","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.031","url":null,"abstract":"<p><strong>Background: </strong>Short-chain fatty acids (SCFAs), produced by anaerobic bacteria through fermentation in the gut, may suppress eosinophilic inflammation while potentially promoting neutrophilic inflammation. However, the role of local SCFAs in airway microbiome, inflammation, and mucus plugging in type 2 dominant obstructive airway diseases remains unclear.</p><p><strong>Objective: </strong>To investigate associations between sputum SCFAs and the relative abundance of anaerobic bacteria, neutrophil and eosinophil counts in sputum, and mucus plug scores on computed tomography (CT) in patients with obstructive airway diseases.</p><p><strong>Methods: </strong>Sputum samples and chest CT were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Sputum samples were analyzed for SCFAs concentrations, including n-butyrate, acetate, and propionate, microbiome composition using 16S rRNA sequencing, and inflammatory cell differentials.</p><p><strong>Results: </strong>In 46 patients, enriched for ACO with relatively high type 2 markers, higher SCFA levels were associated with higher relative abundance of phylum Bacteroidetes and lower relative abundance of phylum Proteobacteria. Hierarchical clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the two neutrophilic clusters, one characterized by higher SCFAs levels and the other by lower SCFAs levels, lower butyrate levels were significantly associated with higher mucus plug scores.</p><p><strong>Conclusion: </strong>Local SCFA concentrations may be closely associated with the airway microbiome and influence mucus plugging in ACO-enriched populations. Understanding these interactions could inform therapeutic strategies targeting SCFAs or the microbiome to manage type 2 dominant obstructive airway diseases.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364778","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":"Clinical, immunologic and genetic characteristics of 148 patients with NK cell deficiency.","authors":"Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahaptra, Debra Canter, Tram Cao, Linda M Shawver, Sara Nandiwada, James R Lupski, Jennifer Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange","doi":"10.1016/j.jaci.2025.01.030","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.030","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.</p><p><strong>Objective: </strong>We sought to define the clinical, immunologic and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type, and guide future research and clinical practice.</p><p><strong>Methods: </strong>During 2006-2022, 168 individuals suspected of having NKD were enrolled, with comprehensive clinical, immunological and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.</p><p><strong>Results: </strong>NK cell abnormalities consistent with NKD were confirmed in 148 individuals. Most presented during childhood (median age 13y, range 0-76y), though 34% were adults. All tested individuals exhibited reduced NK cell cytotoxic function; 44% also had decreased NK cell numbers and/or mature NK cells. Herpesvirus and/or papillomavirus infections were observed in 71%, malignancies in 7%, and a 5% case-fatality rate was noted. Among the 99 individuals who underwent research exome sequencing, 29% were considered solved for a likely contributing variant allele, 52% of these cases involving known genes and 48% involving novel genes.</p><p><strong>Conclusions: </strong>NKD is a phenotypic immunodeficiency associated with increased susceptibility to certain viral infections and cancer, with multiple genetic etiologies, revealing key biological pathways for NK cell development and function. This research underscores the role of NK cells in human immune defenses, and helps advance the identification of at-risk populations, precise genetic diagnoses, and informed clinical management for those with NKD.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364774","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":"Outcome of hematopoietic stem cell transplantation for SCID and impact of newborn screening on overall survival - A single referral center study.","authors":"Chen Anchoo, Atar Lev, Amos J Simon, Shiran Levy, Amarilla Mandola, Shirly Frizinsky, Ido Somekh, NaserEddin Adeeb, Rabee S A Adwan, Amos Toren, Hana Golan, Bella Bielorai, Daphna Hutt, Etai Adam, Raz Somech","doi":"10.1016/j.jaci.2025.01.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.029","url":null,"abstract":"<p><strong>Background: </strong>Hematopoietic stem cell transplantation (HSCT) is a curative treatment for infants with severe combined immunodeficiency (SCID). Different factors determine HSCT success and overall survival (OS). Specifically, prompt diagnosis of SCID, preferably through newborn screening (NBS), is critical.</p><p><strong>Objective: </strong>To explore variable factors including the impact of NBS that are associated with HSCT outcomes and OS, in a multi-ethnic SCID cohort.</p><p><strong>Methods: </strong>100 SCID patients diagnosed and treated with HSCT at Sheba Medical Center in Israel between the years 1996 to 2024 were studied.</p><p><strong>Results: </strong>We distinguished three groups: Palestinians (62%), Israeli Jews (16%), and Israeli non-Jews (22%). The OS rate was 68%, increasing to 84% when excluding mortality in the first month post-transplantation. Better outcomes were significantly associated with the use of bone marrow (BM) as a stem cell source (P =0.003), the availability of matched related donors (MRD, P =0.045) and use of conditioning (P =0.0006). Due to delayed diagnosis, Palestinian patients had more infections, more events of early post-HSCT death, and inferior OS rates compared to other patients. SCID cases identified by NBS demonstrated superior OS (93%) compared to cases identified by clinical presentation (P =0.04). Improvement in OS was most significant following the implementation of the NBS program for SCID in Israel (P = 0.03).</p><p><strong>Conclusion: </strong>Our study delineates and reinforces specific factors that influence OS after undergoing HSCT for SCID. Importantly, it raises the value of early diagnosis and treatment of affected infants, highlighting the benefit of NBS for SCID in determining the clinical outcome.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122775","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}