Clinical and experimental immunology最新文献

{"title":"Mimics and challenging presentations of DADA2.","authors":"Admir Öztürk, Lara Yagci, Serdal Ugurlu","doi":"10.1093/cei/uxaf017","DOIUrl":"10.1093/cei/uxaf017","url":null,"abstract":"<p><p>Deficiency of adenosine deaminase 2 (DADA2) has been a challenging diagnosis to make since it was first described in 2014. The disease represents a wide range of phenotypes. Therefore, it may present with various clinical patterns. Throughout the years, several difficult-to-diagnose cases of DADA2 were reported in the literature. Although several studies and reviews were published regarding different phenotypes and manifestations of DADA2, a review of challenging cases with diverse combinations of DADA2 manifestations was needed to integrate the knowledge from the literature into the clinical practice. Immunological, hematologic, autoinflammatory, and adult-onset polyarteritis-nodosa patterns were reported in the literature as cases challenging to diagnose. In this review, we aim to summarize the challenging case reports from the literature, provide an algorithmic approach for these kinds of presentations, and share our perspective and recommendations on the topic. Diagnosing DADA2 on time is a vital issue for preventing fatal and debilitating vascular events with anti-TNF-alpha therapy. Thus, early testing for DADA2 in suspected cases is recommended. Family history and genetic testing of the patient and the first-degree relatives are essential for accurate diagnosis. Thorough systemic examination and imaging might help detect clinically silent findings of vasculitis. Enzymatic activity of ADA2, when available, is also a key diagnostic tool that complements genetic testing and clinical evaluation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease.","authors":"Alexander Schnell, Carmen Aicher, Philipp A Schnegelsberg, Benedikt Schwarz, Hannah Schmidt, Ida Allabauer, Aline Rueckel, Adrian P Regensburger, Joachim Woelfle, André Hoerning","doi":"10.1093/cei/uxae066","DOIUrl":"10.1093/cei/uxae066","url":null,"abstract":"<p><p>T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. Twenty-one responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17-shifted phenotype. The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis.","authors":"Katie J Smith, Zachary Lim, Sonja Vermeren, Veronique E Miron, Sarah Dimeloe, Donald J Davidson, Anna Williams, Emily Gwyer Findlay","doi":"10.1093/cei/uxae115","DOIUrl":"10.1093/cei/uxae115","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterized. Here we focussed on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular overabundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective analysis of the number and function of two T regulatory cell subsets in healthy individuals.","authors":"Erick Colunga-Bolaños, Lesly Doniz-Padilla, Marlen Vitales-Noyola, Larisa González-Baranda, Berenice Hernández-Castro, Perla Niño-Moreno, Diana P Portales-Pérez, Roberto González-Amaro","doi":"10.1093/cei/uxaf025","DOIUrl":"10.1093/cei/uxaf025","url":null,"abstract":"<p><strong>Introduction: </strong>T regulatory (Treg) cells play a crucial role in immune system homeostasis and in the pathogenesis of immune-mediated inflammatory diseases. Accordingly, numerous studies have examined the number and function of these lymphocytes in patients with different conditions as well as in healthy controls. The aim of this study was to analyze potential variations in the number and function of two Treg cell subsets in healthy adults over a 2-month period.</p><p><strong>Methods: </strong>In a pilot study, blood samples were collected from 20 healthy individuals on Days 0, 30, and 60, and the levels of natural Treg cells (CD4+CD25highFoxp3+) and CD69+ Treg cells (CD4+CD69+CD25-/+LAP+IL-10+Foxp3-) were analyzed by flow cytometry. In addition, the function of these regulatory cells was evaluated using an in vitro assay that measures the inhibition of activation of autologous T lymphocytes.</p><p><strong>Results: </strong>Although no significant differences were observed across the three serial measurements of the number or function of the Treg cells analyzed (P > 0.05 in both cases), a substantial proportion of individuals showed notable changes (either an increase or decrease) in these parameters during the study. These variations were not apparently associated with any factors affecting immune system homeostasis, including infections, medication use, or immunizations.</p><p><strong>Conclusion: </strong>Our findings suggest that significant fluctuations of causes to be determined occur in the levels and function of Treg cells in healthy individuals. This phenomenon should be considered in studies investigating immunoregulation in humans.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type I interferon signature: a quantitative standardized method for clinical application.","authors":"Alessandra Tesser, Paola Bocca, Massimo Ulivi, Alessia Pin, Claudia Pastorino, Davide Cangelosi, Elettra Santori, Enrico Drago, Roberta Caorsi, Fabio Candotti, Marco Gattorno, Alberto Tommasini, Stefano Volpi","doi":"10.1093/cei/uxaf018","DOIUrl":"10.1093/cei/uxaf018","url":null,"abstract":"<p><p>Type I Interferon (IFN) induced gene expression analysis (\"IFN signature\") is employed to categorize pathological conditions that exhibit Type I IFN dysregulation and to direct customized therapeutic strategies. For instance, it is used to differentiate patients with IFN-related inflammation from those with conditions primarily mediated by other cytokines, such as juvenile idiopathic arthritis and periodic fevers. Nevertheless, there is currently no standardized method available for clinical practice, and comparing values at different time points or between centers poses a challenge. In this work, we described a standardized method based on the development and validation of a synthetic control to solve the problem of test comparison. Inter-assay and inter-laboratory variability were assessed by multiple repeated analyses within the same laboratory, and between two different laboratories involved in the study. The method has been validated by evaluating the IFN signature of 39 patients with inflammatory disorders known to be related or not to Type I IFN (i.e. monogenic interferonopathies, systemic lupus erythematosus, juvenile dermatomyositis, periodic fevers, and juvenile idiopathic arthritis). The proposed method proved to be highly reproducible among centers and able to discriminate among IFN-related or non-IFN-related inflammation. The use of a synthetic control minimized the inter-assay and inter-laboratory variability, and thus facilitate data sharing among centers to improve knowledge of IFN-related inflammation and patient's care.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C/EBPε and its acetylation in PMN enhance the tolerance to trauma.","authors":"Shaowen Cheng, Junyu Zhu, Yangyang Bian, Jiangling Yao, Wei Zhang, Shuangqin Yin, Tianyin Kuang, Lina Xian, Huaping Liang","doi":"10.1093/cei/uxae061","DOIUrl":"10.1093/cei/uxae061","url":null,"abstract":"<p><p>Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of polymorphonuclear neutrophils (PMNs) undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of PMNs, a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. Therapeutic interventions, whether through the sole administration of PMN, nicotinamide (NAM) treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating T-cell-derived extracellular vesicles as biomarkers of disease activity, axonal injury, and disability in multiple sclerosis.","authors":"Jennifer L Zagrodnik, Stephanie N Blandford, Neva J Fudge, Shane T Arsenault, Sarah Anthony, Lillian McGrath, Fraser Clift, Mark Stefanelli, Craig S Moore","doi":"10.1093/cei/uxaf003","DOIUrl":"10.1093/cei/uxaf003","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system, whereby clinical disease activity is primarily monitored by magnetic resonance imaging.</p><p><strong>Methods: </strong>Given the limitations associated with implementing and acquiring novel and emerging imaging biomarkers in routine clinical practice, the discovery of biofluid biomarkers may offer a more simple and cost-effective measure that would improve accessibility, standardization, and patient care. Extracellular vesicles (EVs) are nanoparticles secreted from cells under both homeostatic and pathological states, and have been recently investigated as biomarkers in MS. The objectives of this study were to longitudinally measure levels of specific immune cell-derived EVs in MS and provide evidence that EV sub-populations may serve as biomarkers of disease activity, axonal injury, and/or clinical disability.</p><p><strong>Results: </strong>Our results demonstrate that the rate of clinical disability in MS negatively correlates with changes in circulating CD3+ EVs within the plasma. Additionally, numbers of CD4+ EVs decrease in individuals with increasing pNfL levels overtime whereby the magnitude of the pNfL increase negatively correlates with changes in plasma CD4+ and CD8+ EVs. Finally, when applying NEDA-3 criteria to define active versus stable disease, individuals with active disease had significantly elevated CD4+ and CD8+ EVs compared to stable disease.</p><p><strong>Conclusion: </strong>In summary, the analysis of specific immune cell-derived EV subsets may provide a method to monitor disability accumulation, disease activity, and axonal injury in MS, while also providing insights into the pathophysiology and cellular/molecular mechanisms that influence progression.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From acute lung injury to cerebral ischemia: a unified concept involving intercellular communication through extracellular vesicle-associated miRNAs released by macrophages/microglia.","authors":"Xianbin Wang, Ting Wang, Dong Zhu, Jing Wang, Weijie Han","doi":"10.1093/cei/uxae105","DOIUrl":"10.1093/cei/uxae105","url":null,"abstract":"<p><p>Ischemic stroke and acute lung injury are prevalent life-threatening conditions marked by intricate molecular mechanisms and elevated mortality rates. Despite evident pathophysiological distinctions, a notable similarity exists in the gene responses to tissue injury observed in both pathologies. This similarity extends to both protein-encoding RNAs and non-coding RNAs. Extracellular vesicles (EVs) are nano-scale vesicles derived through cell secretion, possessing unique advantages such as high biocompatibility, low immunogenicity, intrinsic cell targeting, and facile chemical and genetic manipulation. Importantly, miRNAs, the most prevalent non-coding RNAs, are selectively concentrated within EVs. Macrophages/microglia serve as immune defense and homeostatic cells, deriving from progenitor cells in the bone marrow. They can be classified into two contrasting types: classical proinflammatory M1 phenotype or alternative anti-inflammatory M2 phenotype. However, there exists a continuum of various intermediate phenotypes between M1 and M2, and macrophages/microglia can transition from one phenotype to another. This review will investigate recent discoveries concerning the impact of EVs derived from macrophages/microglia under various states on the progression of ischemic stroke and acute lung injury. The focus will be on the involvement of miRNAs within these vesicles. The concluding remarks of this review will underscore the clinical possibilities linked to EV-miRNAs, accentuating their potential as both biomarkers and therapeutic targets.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century.","authors":"Leila Janani, Rachel Phillips, Ellie Van Vogt, Xinxue Liu, Claire Waddington, Suzie Cro","doi":"10.1093/cei/uxae104","DOIUrl":"10.1093/cei/uxae104","url":null,"abstract":"<p><p>Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomized controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study.","authors":"John Whalen, Anita Chandra, Sven Kracker, Stephan Ehl, Markus G Seidel, Ioana Gulas, Louis Dron, Russanthy Velummailum, Chenthila Nagamuthu, Sichen Liu, Joanne Tutein Nolthenius, Maria Elena Maccari","doi":"10.1093/cei/uxae107","DOIUrl":"10.1093/cei/uxae107","url":null,"abstract":"<p><p>Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: -1.09 g/L; 95% CI: -1.78, -0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}