Journal of Allergy and Clinical Immunology最新文献

{"title":"Unravelling the noise in pharmacokinetic studies of epinephrine: Time to focus on cardiac output?","authors":"Nandinee Patel, Lucy Hawkins, Paul J Turner","doi":"10.1016/j.jaci.2024.10.026","DOIUrl":"10.1016/j.jaci.2024.10.026","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621013","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":"IL-9 sensitizes human T_H2 cells to proinflammatory IL-18 signals in atopic dermatitis.","authors":"Stefanie Schärli, Fabian Luther, Jeremy Di Domizio, Christina Hillig, Susanne Radonjic-Hoesli, Kathrin Thormann, Dagmar Simon, Amalie Thorsti Møller Rønnstad, Iben Frier Ruge, Blaine G Fritz, Thomas Bjarnsholt, Angela Vallone, Sanja Kezic, Michael P Menden, Lennart M Roesner, Thomas Werfel, Jacob P Thyssen, Stefanie Eyerich, Michel Gilliet, Nicole L Bertschi, Christoph Schlapbach","doi":"10.1016/j.jaci.2024.10.027","DOIUrl":"10.1016/j.jaci.2024.10.027","url":null,"abstract":"<p><strong>Background: </strong>T_H2 cells crucially contribute to the pathogenesis of atopic dermatitis (AD) by secreting high levels of IL-13 and IL-22. Yet the upstream regulators that activate T_H2 cells in AD skin remain unclear. IL-18 is a putative upstream regulator of T_H2 cells because it is implicated in AD pathogenesis and has the capacity to activate T cells.</p><p><strong>Objective: </strong>We sought to decipher the role of IL-18 in T_H2 responses in blood and skin of AD patients.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells and skin biopsy samples from AD patients and healthy donors were used. Functional assays were performed ex vivo using stimulation or blocking experiments. Analysis was performed by flow cytometry, bead-based multiplex assays, RT-qPCR, RNA-Seq, Western blot, and spatial sequencing.</p><p><strong>Results: </strong>IL-18Rα⁺ T_H2 cells were enriched in blood and lesional skin of AD patients. Of all the cytokines for which T_H2 cells express the receptor, only IL-9 was able to induce IL-18R via an IL-9R-JAK1/JAK3-STAT1 signaling pathway. Functionally, stimulation of circulating T_H2 cells with IL-18 induced secretion of IL-13 and IL-22, an effect that was enhanced by costimulation with IL-9. Mechanistically, IL-18 induced T_H2 cytokines via activation of IRAK4, NF-κB, and AP-1 signaling in T_H2 cells, and neutralization of IL-18 inhibited these cytokines in cultured explants of AD skin lesions. Finally, IL-18 protein levels correlated positively with disease severity in lesional AD skin.</p><p><strong>Conclusion: </strong>Our data identify a novel IL-9/IL-18 axis that contributes to T_H2 responses in AD. Our findings suggest that both IL-9 and IL-18 could represent upstream targets for future treatment of AD.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620973","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":"Integrative epidemiology and immunotranscriptomics uncover a risk and potential mechanism for cutaneous lymphoma unmasking or progression with dupilumab therapy.","authors":"Javier S Cabrera-Perez, Vincent J Carey, Oreofe O Odejide, Sonal Singh, Thomas S Kupper, Shiv S Pillai, Scott T Weiss, Ayobami Akenroye","doi":"10.1016/j.jaci.2024.10.028","DOIUrl":"10.1016/j.jaci.2024.10.028","url":null,"abstract":"<p><strong>Background: </strong>There have been multiple reports of the anti-IL-4Rα agent, dupilumab, being associated with the onset and/or progression of cutaneous T-cell lymphoma (CTCL).</p><p><strong>Objective: </strong>We sought to evaluate safety signals associated with dupilumab, with a focus on CTCL, and to evaluate the possible underlying mechanism or mechanisms for the potential association.</p><p><strong>Methods: </strong>First, we used the Food and Drug Administration's pharmacovigilance database, FAERS (FDA Adverse Event Reporting System), to evaluate whether dupilumab was associated with CTCL, including both positive outcome controls (conjunctivitis, eosinophilia, and arthralgia) and exposure controls (other medications with similar indications, including JAK inhibitors and the anti-IL-13 agent, tralokinumab) to evaluate confounding bias. Thereafter, we used publicly available bulk and single-cell RNA sequencing datasets to probe possible underlying mechanisms through which dupilumab might be associated with CTCL.</p><p><strong>Results: </strong>Between January 2017 and the fourth quarter of 2023, there were 181,575 unique reports of dupilumab-related adverse events (AEs) in FAERS, with 606 of these being for a neoplasm. Dupilumab had 30.0 times the proportional reporting ratio (PRR) (95% confidence interval, 25.0-35.9) for CTCL compared to all other medications in FAERS. The risk was highest in men aged 45 to 65. The PRR for conjunctivitis, eosinophilia, and arthralgia, known adverse effects of dupilumab, were 35.6 (34.4-36.8), 2.15 (2.00-2.31), and 2.14 (2.07-2.18), respectively. Using the log-count normalized PRR (AE score) to account for PRR inflation when reports were small, the top safety signals included conjunctivitis (AE score 8.3) and CTCL (AE score 4.9). Bulk RNA sequencing data showed changes in IL-4RA and IL-13RA1 expression in CTCL and in epidermal layers of atopic dermatitis (AD) biopsy samples. Single-cell transcriptomic studies revealed that this change was similar in AD and CTCL, and that keratinocytes seemed to be the most divergent cell type with regards to IL-4R and IL-13RA1. An effect on keratinocyte-specific gene expression was also independently observed in available bulk RNA sequencing data.</p><p><strong>Conclusion: </strong>These data suggest that dupilumab might be causing an unmasking or progression of CTCL via the same mechanism through which it improves AD: IL-13 receptor blockade, which leads to increased IL-13 in the local milieu, driving CTCL stimulation and progression. However, these associations need further evaluation given the inherent limitations of the FAERS database and our nonexperimental approach.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620978","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":"IgG4 and eosinophilic esophagitis: Bridging the knowledge gap.","authors":"Laura Franceschini, Alessandro Farsi","doi":"10.1016/j.jaci.2024.09.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.029","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620971","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":"Association between allergic diseases and mental health conditions: An umbrella review.","authors":"Xianpeng Xu, Sha Li, Yingjie Chen, Xinxing Deng, Jiongke Li, Dajing Xiong, Hui Xie","doi":"10.1016/j.jaci.2024.10.030","DOIUrl":"10.1016/j.jaci.2024.10.030","url":null,"abstract":"<p><strong>Background: </strong>The mental health conditions of allergic diseases have been investigated, but the consistency and magnitude of their effects are unclear. The aim of this umbrella review was to systematically evaluate the published evidence on allergic diseases and mental health conditions to establish a new hierarchy of evidence and identify gaps in this area of research.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from database inception to April 30, 2024. We included systematic reviews that conducted meta-analyses that examined the association of allergic diseases and mental health conditions. We calculated summary effect estimates (odds ratios), 95% confidence intervals, I² statistics, 95% prediction intervals, small study effects, and excess significance biases. We used AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2) to appraise the methodologic quality of the included studies.</p><p><strong>Results: </strong>We identified 21 eligible articles, which yielded 37 associations (348,405,029 total population) of allergic diseases and mental health conditions. The credibility of evidence was convincing (class I) for asthma and risk of attention-deficit/hyperactivity disorder (odds ratio 1.34, 95% confidence interval 1.24-1.44); and highly suggestive (class II) for allergic rhinitis and risk of tic disorders (2.61, 1.90-3.57), allergic rhinitis and risk of sleep disorders (2.17, 1.87-2.53), food allergy and risk of autism spectrum disorder (2.79, 2.08-3.75), atopic dermatitis and risk of depression (1.60, 1.43-1.79), atopic dermatitis and risk of anxiety (1.62 1.42-1.85), atopic dermatitis and risk of attention-deficit/hyperactivity disorder (1.28, 1.18-1.40), atopic dermatitis and risk of suicidal ideation (1.44, 1.25-1.65), asthma and risk of depression (1.64, 1.50-1.78), asthma and risk of anxiety (1.95, 1.68-2.26), asthma and risk of tic disorders (1.90, 1.57-2.30), asthma and risk of suicidal ideation (1.52, 1.37-1.70), and asthma and risk of suicide attempts (1.60, 1.33-1.92).</p><p><strong>Conclusions: </strong>Allergic diseases are associated with increased risk of a range of mental health conditions, with the most convincing evidence for asthma. However, these associations do not imply causality, and there is large heterogeneity in these associations, which requires high-quality primary studies to identify causality and strength of evidence.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620963","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":"Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitors.","authors":"P Abigail Alvarado-Vazquez, Erika Mendez-Enriquez, Maya Salomonsson, Peter Kopac, Ana Koren, Urska Bidovec-Stojkovic, Sabina Škrgat, Oscar E Simonson, Valentyna Yasinska, Sven-Erik Dahlén, Gunnar Pejler, Christer Janson, Peter Korosec, Andrei Malinovschi, Jenny Hallgren","doi":"10.1016/j.jaci.2024.10.025","DOIUrl":"10.1016/j.jaci.2024.10.025","url":null,"abstract":"<p><strong>Background: </strong>Therapies targeting IL-5 or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma.</p><p><strong>Objective: </strong>We sought to investigate the impact of anti-IL-5 and anti-IL-5Rα biological therapies on mast cells (MCs) and their progenitors.</p><p><strong>Methods: </strong>Surface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow and in human lungs and blood. Isolated human MC progenitors cultured in the presence or absence of IL-5 were analyzed in vitro. Circulating MC progenitors were quantified in patients with severe asthma before and after anti-IL-5 (mepolizumab) or anti-IL-5Rα (benralizumab) therapy. Gene expression analysis of MC progenitors was performed before and after anti-IL-5Rα therapy.</p><p><strong>Results: </strong>Approximately 50% of the human primary lung MCs and 30% of the human MC progenitors from individuals with allergic asthma expressed IL-5Rα. In patients with mild to moderate allergic asthma and mice with acute allergic airway inflammation, the fraction of IL-5Rα⁺ MC progenitors was elevated. In addition, IL-5 promoted the proliferation and/or survival of isolated human MC progenitors. Furthermore, patients with severe asthma from 2 independent cohorts demonstrated a reduction in blood MC progenitors after anti-IL-5 or anti-IL-5Rα treatment. This was associated with improved asthma control as well as a decline in both blood eosinophils and T_H2 cells. Finally, the blood MC progenitors remaining after anti-IL-5Rα (benralizumab) treatment exhibited a downregulated expression of genes involved in growth and proliferation.</p><p><strong>Conclusions: </strong>This study introduces the possibility that the clinical effects of targeting IL-5/IL-5Rα in severe asthma may also involve reduction of MC populations.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621004","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":"Current status and future directions in food protein-induced enterocolitis syndrome: An NIAID workshop report of the June 22, 2022, virtual meeting.","authors":"Anna Nowak-Wegrzyn, Scott H Sicherer, Cem Akin, Sara Anvari, Lisa M Bartnikas, M Cecilia Berin, Theresa A Bingemann, Scott Boyd, Terri Brown-Whitehorn, Supinda Bunyavanich, Antonella Cianferoni, George du Toit, John E Fortunato, Jeffrey D Goldsmith, Marion Groetch, Stephanie A Leonard, Meenakshi Rao, Fallon Schultz, Julie M Schwaninger, Carina Venter, Amity Westcott-Chavez, Robert A Wood, Alkis Togias","doi":"10.1016/j.jaci.2024.10.022","DOIUrl":"10.1016/j.jaci.2024.10.022","url":null,"abstract":"<p><p>Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy characterized by delayed, protracted vomiting and accompanied by lethargy and pallor, usually 1 to 4 hours after ingesting the food allergen. The pathophysiology of FPIES remains unknown, and currently there are no diagnostic biomarkers available to assess disease activity or its resolution. Over the last 2 decades, FPIES has become increasingly recognized in both pediatric and adult patients. Forty years after the initial FPIES description, the first FPIES code appeared in the International Classification of Diseases, Tenth Revision (ICD-10), and the first international consensus guidelines for the diagnosis and management of FPIES were published. On June 22, 2022, the National Institute of Allergy and Infectious Diseases (NIAID) held its first virtual multidisciplinary workshop on FPIES. Various clinical and translational aspects of FPIES as well as important areas of unmet needs were discussed as priorities for future research during this 2-day virtual workshop. Our report provides a summary of content of the workshop, including updated literature on the topic areas, and also provides critical commentary on the state of FPIES.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620969","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":"Newborn screening for SCID and severe T lymphocytopenia in Europe.","authors":"Maartje Blom, Maarja Soomann, Pere Soler-Palacín, Anna Šedivá, Asbjørg Stray-Pedersen, Rolf Zetterström, Carsten Speckmann, Andrew R Gennery, Mirjam van der Burg","doi":"10.1016/j.jaci.2024.10.018","DOIUrl":"10.1016/j.jaci.2024.10.018","url":null,"abstract":"<p><p>Initiation of newborn screening (NBS) programs in Europe dates back to the 1960s. One of the most recent expansions of NBS programs was the addition of severe combined immunodeficiency (SCID) based on detection of T-cell receptor excision circles (TRECs). In this review, we present an overview of the current situation in Europe. To avoid a biased overview based on only published results, a 37-item survey on TREC-based NBS was sent to representatives of 46 European countries. With a response rate of 83%, we collected data of 38 countries. Seventeen of the 38 European countries that have completed the survey have nationally or regionally implemented TREC-based NBS. The survey results emphasize similarities and differences as well as common practices and challenges in TREC-based NBS. Because TRECs are a general surrogate marker for severe T lymphocytopenia, conditions other than SCID are also identified. Therefore, the initial definition of the target disease as \"SCID\" might need to be reconsidered and extended to \"SCID and severe T lymphocytopenia.\" Even though complete harmonization of TREC-based NBS programs across Europe will remain challenging, collaboration and close partnerships will help in the move toward universal TREC-based screening for all newborns, resulting in more infants with SCID and severe T lymphocytopenia being detected each year.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604993","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":"Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial.","authors":"Maria Suprun, Ashley Sang Eun Lee, Robert Getts, Simon Peck, Sayantani B Sindher, Kari C Nadeau, R Sharon Chinthrajah, Stephen J Galli, Hugh A Sampson","doi":"10.1016/j.jaci.2024.10.017","DOIUrl":"10.1016/j.jaci.2024.10.017","url":null,"abstract":"<p><strong>Background: </strong>Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut.</p><p><strong>Objective: </strong>We sought to determine whether patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization.</p><p><strong>Methods: </strong>Subjects in the POISED trial (NCT02103270) were randomized to peanut (n = 95) or placebo (n = 25) for 24 months. Oral immunotherapy-desensitized subjects were then assigned to no peanut (PN-0) (n = 51) or 300 mg peanut (PN-300) (n = 30) for 12 months. SU and SHT were determined by subjects in PN-0 and PN-300, respectively, passing 4000-mg peanut oral challenge. Specific IgE and IgG₄ levels to peanut; Ara h 1, Ara h 2, and Ara h 3 proteins; and 64 allergenic epitopes were measured. We developed machine learning models with bootstrap simulations using baseline data to predict SU/SHT.</p><p><strong>Results: </strong>Of 80 (84%) subjects who were desensitized to peanut, 13% (n = 8) and 37% (n = 13) achieved SU/SHT in PN-0 and PN-300 groups. Decreases in epitope-and protein-specific IgE levels and increases in IgG₄ levels were observed during 2 years of oral immunotherapy. At baseline, patients with SU in PN-0, but not PN-300, group had lower epitope-specific IgE and protein-specific IgE levels compared with the transient desensitization group. A machine learning model with 12 baseline epitope-specific IgEs and age could predict SU/SHT with accuracy of 94%, area under the curve 0.97, sensitivity 1.00, and specificity 0.91.</p><p><strong>Conclusions: </strong>Subjects who achieved SU/SHT had different baseline protein- and epitope-specific IgE profiles than subjects with transient desensitization. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590625","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":"Association of CD19⁺-targeted chimeric antigen receptor (CAR) T-cell therapy with hypogammaglobulinemia, infection, and mortality.","authors":"Natalia M Sutherland, Baijun Zhou, Lingxiao Zhang, Mei-Sing Ong, Joseph S Hong, Andrew Pak, Katherine J Liu, Matthew J Frigault, Marcela V Maus, Joshua A Hill, Kerry Reynolds, Jolan E Walter, Carlos A Camargo, Sara Barmettler","doi":"10.1016/j.jaci.2024.10.021","DOIUrl":"10.1016/j.jaci.2024.10.021","url":null,"abstract":"<p><strong>Background: </strong>CD19-targeted chimeric antigen receptor T-cell therapy (CAR-T therapy) has revolutionized the treatment of hematologic malignancies. As these cells target CD19⁺ receptors on B cells, there is the potential for B-cell aplasia and hypogammaglobulinemia. Data on the degree and clinical significance of hypogammaglobulinemia are sparse.</p><p><strong>Objectives: </strong>We sought to evaluate hypogammaglobulinemia after CD19-targeted CAR-T therapy and risk factors for hypogammaglobulinemia, infections, and mortality.</p><p><strong>Methods: </strong>We performed a retrospective evaluation of 579 patients receiving CD19-directed CAR-T therapy and evaluated demographics, hypogammaglobulinemia (IgG ≤600 mg/dL), infections prior to and after CAR-T therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality.</p><p><strong>Results: </strong>Patients had a mean age of 64 years and 64% were male. Prior to CAR-T therapy, 60% of patients had hypogammaglobulinemia, which increased to 91% post-CAR-T therapy. Mean IgG levels decreased from pre- to post-CAR-T therapy levels (587 to 362 mg/dL; P < .0001). Thirty-seven percent of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia prior to CAR-T therapy was associated with worsening hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia post CAR-T therapy was associated with an increased risk of serious infection following CAR-T therapy (incidence rate ratio: 2.7; 95% CI: 1.5-5.2; P = .002). Risk factors for mortality included mild hypogammaglobulinemia (400 mg/dL < IgG ≤ 600 mg/dL), infections ≤100 days post-CAR-T therapy, and hospitalizations for infections. Immunoglobulin replacement was associated with a decreased risk of mortality.</p><p><strong>Conclusions: </strong>We identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia before CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia after CAR-T therapy, which was associated with an increased risk of serious infection and mortality post CAR-T therapy. Increased immunological monitoring is needed to identify high-risk patients who may benefit from interventions to decrease morbidity and mortality.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590530","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}