Clinical & Translational Immunology最新文献

{"title":"Genetic differences in the HLA region contribute to the variability in SARS-CoV-2 vaccine responsiveness of older persons: the Doetinchem Cohort Study","authors":"Yunus Kuijpers,&nbsp;M Liset Rietman,&nbsp;H Susan J Picavet,&nbsp;Peter Engelfriet,&nbsp;W M Monique Verschuren,&nbsp;Anne-Marie Buisman","doi":"10.1002/cti2.70058","DOIUrl":"10.1002/cti2.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Older persons generally have weaker antibody responses to vaccines than younger individuals, but heterogeneity is large. We aimed to identify genetic variants associated with primary SARS-CoV-2 vaccine-induced antibody responses in older persons that might contribute to this heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Demographic and genotype data were collected in the Doetinchem Cohort Study prior to the COVID-19 pandemic. Antibody responses were measured 1 month after the first and second SARS-CoV-2 vaccinations, and genome-wide association analysis was performed in 842 and 890 individuals respectively. Polygenic scores were calculated and tested in an independent sample, and the variance explained by the scores was estimated using a bootstrap procedure. Genes were mapped to genome-wide suggestive (<i>P</i> &lt; 1 × 10⁻⁵) loci, and gene set enrichment was performed using the hypergeometric test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Antibody responses 1 month after the first and second SARS-CoV-2 vaccinations were linked to genome-wide significant (<i>P</i> &lt; 5 × 10⁻⁸) loci on Chromosome 5. Polygenic scores related to these antibody responses could explain 9% (95% CI P1: [−4% to 21%], 95% CI P2: [−4% to 24%]) of the variance. Genome-wide suggestive loci related to the responses after two vaccinations could be mapped to several genes in the human leukocyte antigen (HLA) region on chromosome 6p21.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Genetic variation is suggested to play a role in the primary vaccine-induced IgG antibody responses to SARS-CoV-2 in older persons. The most prominent source of variation was found to lie in HLA genes, which are enriched in several immune pathways and immune-mediated diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12588338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin immunity and inflammation: cellular interactions and communication","authors":"Divyaa Narayanan,&nbsp;Seen Ling Sim,&nbsp;Snehlata Kumari","doi":"10.1002/cti2.70053","DOIUrl":"10.1002/cti2.70053","url":null,"abstract":"<p>The skin is a vital organ that protects organisms from external insults, providing a barrier to the outside environment. The cellular system of the skin consists of highly specialised immune and non-immune cells, which are equipped to respond promptly, providing effective immunity and restoring tissue homeostasis. Well-coordinated cellular communication involves cells and soluble factors, which are essential for maintaining the balance and protecting the skin from inflammatory skin diseases, impaired tissue repair and recurring infections. In this review, we will focus on the recent development of understanding how cellular networks orchestrate skin immunity via a coordinated communication system of soluble factors and their signalling pathways, with a focus on psoriasis as a model of inflammatory skin disease.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12581170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-dimensional spectral cytometry identifies follicular regulatory CD8+ T cells in diffuse large B-cell lymphoma","authors":"Alba Díaz Herrero,&nbsp;Phuong-Ha Le,&nbsp;Loic Renaud,&nbsp;Véronique Meignin,&nbsp;Catherine Thieblemont,&nbsp;Véronique Blanc,&nbsp;Vassili Soumelis,&nbsp;Pierre Tonnerre","doi":"10.1002/cti2.70062","DOIUrl":"10.1002/cti2.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL) constitutes 30–40% of non-Hodgkin lymphoma cases. Despite therapeutic advances, persistence of relapsed cases has been linked to the complex tumor microenvironment (TME) and its interactions with lymphoma cells. In particular, characterising T-cell subsets, including rare cell types, and their interplay with the remaining TME is crucial for unravelling DLBCL pathogenesis and refining therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using flow and spectral cytometry with unsupervised analysis, we investigated T-cell subpopulations across DLBCL biopsies and control lymph nodes (LN). We also inferred communication pathways between T cells and other immune cells in the TME based on the correlation of ligand–receptor expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis revealed a higher frequency of CD8⁺ follicular regulatory T (Tfr) cells in DLBCL biopsies compared to control LN. These cells exhibited an effector-memory phenotype (CD45RA⁻ CCR7⁻), expressed follicular markers (PD-1⁺ CXCR5⁺) and had a regulatory profile (CD127⁻ CD25⁺) along with an activation/co-stimulatory signature (HLA-DR⁺, ICOS⁺, CD95⁺). Correlation analysis highlighted a co-stimulatory interaction between lymphoma B cells and CD8⁺ Tfr cells through the ICOS/ICOSL pathway, which may contribute to a protumor effect. Validation in independent scRNAseq and flow cytometry datasets confirmed the notable prevalence of CD8⁺ Tfr cells in DLBCL biopsies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study highlights the utility of high-dimensional computational cytometry in elucidating T-cell subpopulations, including an increased frequency of CD8⁺ follicular regulatory T cells and their communication patterns within the DLBCL TME. This unbiased approach sheds light on novel cellular mechanisms in DLBCL, uncovering potential targets and biomarkers for immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12581182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated high-density lipoprotein levels following acute graft-versus-host disease onset: a potential link to T-cell dysfunction and increased relapse risk","authors":"Romy Böttcher-Loschinski,&nbsp;Franziska Karl,&nbsp;Diana Drettwan,&nbsp;Johannes Wittmann,&nbsp;Benedikt Jacobs,&nbsp;Simon Völkl,&nbsp;Heiko Bruns,&nbsp;Andreas Mackensen,&nbsp;Dimitrios Mougiakakos","doi":"10.1002/cti2.70060","DOIUrl":"10.1002/cti2.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Allogeneic stem cell transplantation (allo-SCT) is the only curative treatment option for several haematologic malignancies. Its therapeutic principle is based on the donor T cells' ability to eliminate any residual malignant cells. Despite its success, challenges such as graft-versus-host disease (GvHD) and disease relapse persist. Recent studies emphasise the role of the metabolic environment in shaping T-cell responses. This study investigates the impact of serum metabolites on T-cell responses following allo-SCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Metabolite levels in serum samples from 55 allo-SCT patients transplanted between November 2015 and October 2018 were analysed by nuclear magnetic resonance (NMR) spectroscopy for six time points after transplantation. These metabolite profiles were correlated with clinical data and T-cell characteristics obtained by flow cytometry-based immunomonitoring. High-density lipoprotein (HDL) emerged as a key factor of interest. To explore the potential relationship between T-cell-related differences and HDL levels, healthy donor T-cell cultures supplemented with HDL were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated HDL levels were associated with acute GvHD (aGvHD) and relapse. Patients with high HDL serum levels exhibited a delayed normalisation of T-cell frequencies and increased effector-memory CD8⁺ T-cell frequencies. <i>In vitro</i> experiments revealed reduced proliferation and expression of activation/effector molecules after exposure to HDL. Effects of HDL on memory T-cell subset formation resembled the <i>in situ</i> findings in patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AGvHD was linked to elevated HDL levels, potentially affecting T-cell-mediated graft-versus-leukaemia (GvL) activity and promoting relapse. HDL could therefore be a potential biomarker for the success of allo-SCT and a lever for improving patients' outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12581179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell subsets in Pneumocystis pneumonia","authors":"Yuxi Chen,&nbsp;Hengmo Rong,&nbsp;Ting Li,&nbsp;Chao Zhang,&nbsp;Huqin Yang,&nbsp;Han Sun,&nbsp;Dong Wang,&nbsp;Xiaoxia Zhou,&nbsp;Kan Zhai,&nbsp;Zhaohui Tong","doi":"10.1002/cti2.70055","DOIUrl":"10.1002/cti2.70055","url":null,"abstract":"<p><i>Pneumocystis</i> pneumonia (PCP), caused by the opportunistic fungal pathogen <i>Pneumocystis</i>, remains a common fungal infection among immunosuppressed individuals. T cells are known to play a critical role in host defences against <i>Pneumocystis</i>. Two functional groups of T cells exist: CD4⁺ T and CD8⁺ T. Distinct subsets of CD4⁺ and CD8⁺ T cells have been shown to participate in PCP development through specific cytokines and interactions with other immune cells, significantly influencing the pulmonary fungal burden and disease severity. However, the host T-cell responses required for an effective adaptive immune response to PCP remain incompletely defined. In this review, we explore how an in-depth understanding of the integrated and well-defined functions of different T-cell subsets in the immune defence against <i>Pneumocystis</i> could provide insights into facilitating the development of anti-<i>Pneumocystis</i> treatment.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12560118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the tumor microenvironment in cholangiocarcinoma to improve immune checkpoint blockade: potential strategies and translational pre-clinical models","authors":"Maria-Danae Jessel,&nbsp;Owen McGreevy,&nbsp;Lauryn McReynolds,&nbsp;Lekh N Dahal,&nbsp;Timothy Gilbert,&nbsp;Hassan Z Malik,&nbsp;Christopher E Goldring,&nbsp;Laura E Randle","doi":"10.1002/cti2.70057","DOIUrl":"https://doi.org/10.1002/cti2.70057","url":null,"abstract":"<p>Cholangiocarcinoma is a malignancy of significant unmet clinical need with limited therapeutic options. Most patients are diagnosed at advanced or metastatic stages, where surgical resection with curative intent is no longer an option. Gemcitabine-cisplatin chemotherapy has been the standard of care for these patients, remaining unchanged for over a decade. Recently, the addition of the programmed death ligand 1 inhibitor, durvalumab, to this regimen demonstrated an objective response rate of 26.7% in a phase III trial, becoming the new standard of care for advanced cholangiocarcinoma. Although considered a success in cholangiocarcinoma treatment, the results indicate that only a small proportion of patients respond to treatment with immune checkpoint inhibitors. Emerging evidence suggests that many cholangiocarcinoma tumors exhibit an immunologically ‘cold’ tumor microenvironment, characterised by predominance of immunosuppressive immune populations and limited infiltration of cytotoxic T cells, which contributes to their resistance to immune checkpoint inhibitors. This review provides a comprehensive overview of the research studies that have employed immunomodulatory strategies in cholangiocarcinoma aimed at priming the tumor microenvironment for a more effective response to immune checkpoint inhibitors. This update will also evaluate the strengths and limitations of current pre-clinical models of cholangiocarcinoma, with emphasis on more advanced translational models. These complex models remain underutilised, hindering the development of novel therapeutic approaches. We suggest that these complex preclinical models may help translation of therapies into clinical practice.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A semi-automated ASC speck assay to evaluate pyrin inflammasome activation","authors":"Pei Dai,&nbsp;Oliver Skinner,&nbsp;Xufeng Lin,&nbsp;Aiden Telfser,&nbsp;Stephanie Ruiz-Diaz,&nbsp;Rohit G Saldanha,&nbsp;Katie Frith,&nbsp;Ming-Wei Lin,&nbsp;Kahn Preece,&nbsp;Paul E Gray,&nbsp;Alberto Pinzon-Charry,&nbsp;Anna Sullivan,&nbsp;Stephen Adelstein,&nbsp;Winnie WY Tong,&nbsp;Matthew JS Parker,&nbsp;Laila Girgis,&nbsp;Brynn Wainstein,&nbsp;Samar Ojami,&nbsp;Elissa K Deenick,&nbsp;Leonard D Goldstein,&nbsp;Michael J Rogers,&nbsp;Tri Giang Phan","doi":"10.1002/cti2.70054","DOIUrl":"https://doi.org/10.1002/cti2.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop a rapid functional assay to validate variants of uncertain significance (VUS) in the <i>MEFV</i> gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Overactivity of the pyrin inflammasome pathway and ASC speck oligomerisation in response to stimulation with low concentrations of <i>Clostridium difficile</i> toxin A was directly visualised by immunofluorescence microscopy. A semi-automated algorithm was developed to count cells and ASC specks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The semi-automated ASC speck assay is able to discriminate between healthy controls and patients with familial Mediterranean fever (FMF) and pyrin inflammasome overactivity with high sensitivity. It is also able to discriminate pyrin inflammasome overactivity from other autoinflammatory disease controls with high specificity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The semi-automated ASC speck assay may be a useful test to functionally validate VUS in the <i>MEFV</i> gene and screen for pyrin inflammasome overactivity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human axillary lymph node T follicular helper (Tfh) and Precursor-Tfh cells exhibit functional flexibility following seasonal influenza vaccination","authors":"Hannah Law,&nbsp;Raymond H. Y. Louie,&nbsp;Omid R. Faridani,&nbsp;Alexandra Carey Hoppé,&nbsp;Mollie Boyd,&nbsp;Mengfei Chen,&nbsp;Jerome Samir,&nbsp;Solange Obeid,&nbsp;Brad Milner,&nbsp;Fabio Luciani,&nbsp;Anthony D. Kelleher,&nbsp;Vanessa Venturi,&nbsp;C. Mee Ling Munier","doi":"10.1002/cti2.70056","DOIUrl":"https://doi.org/10.1002/cti2.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CD4⁺ T cells partitioned into different cell lineages based on transcription factor, cytokine and chemokine expression have defined functions that work cooperatively to ensure optimum operation of the immune system. This study investigated the lineages and interactions of key CD4⁺ T-cell subsets within human lymph nodes (LNs) post-vaccination to assess the potential for adaptability and flexibility in an immune response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ultrasound-guided fine needle biopsies/aspirates were used to isolate T follicular helper (Tfh) and Precursor (Pre)-Tfh cells from the vaccine-draining and contralateral axillary LNs of five individuals at 5 days after influenza vaccination, followed by single-cell RNA sequencing, gene expression and T-cell receptor analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tfh and Pre-Tfh cells within five clusters with distinct gene expression profiles, designated: Resting, Activated migrating, B-cell-interacting Tfh, Proliferating and Cytotoxic, exhibited attributes of more than one T-cell lineage and expanded T-cell clones were present in more than one cluster, suggesting divergent differentiation into different fate lineages from a common precursor. Inferred pseudotime suggested a bifurcating trajectory rooted in the resting cluster and terminating at either the Proliferating or Cytotoxic clusters. This analysis predicted the transition of cells through activation states and the gain and loss of lineage attributes and effector functions. Enriched gene pathways along the pseudotime trajectories were consistent with these functional transitions and involvement in the immune response to vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results reveal the flexible potential within the Tfh lineage that could be leveraged to drive more efficient vaccine responses and inform rational vaccine design.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study and polygenic risk scores of eosinophilia in Taiwan","authors":"Hsing-Fang Lu,&nbsp;Su Boon-Yong,&nbsp;Chi-Ya Yang,&nbsp;Jiu-Yao Wang,&nbsp;Yen-Ting Chang,&nbsp;Fuu-Jen Tsai","doi":"10.1002/cti2.70050","DOIUrl":"https://doi.org/10.1002/cti2.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Eosinophilia, characterised by elevated eosinophil levels, is associated with various allergic and inflammatory conditions. This study aimed to elucidate the genetic determinants of eosinophil levels by examining polygenic risk scores (PRS) and identifying significant single nucleotide polymorphisms (SNPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive genome-wide association study (GWAS) on eosinophil levels using a large cohort, comprising 221 851 controls (eosinophil levels ≤ 5%) and 11 200 cases (eosinophil levels &gt; 5%) in Taiwan. The analysis included covariates such as age, sex and the first 10 principal components to account for population stratification. Polygenic risk scores were calculated, and their associations with eosinophil levels were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The control group exhibited a mean eosinophil level of 47.81 (SD, 21.08) and was composed of 55.32% females and 44.68% males. The case group had a mean eosinophil level of 43.27 (SD, 22.27) and consisted of 38.6% females and 61.4% males. The GWAS identified several SNPs with significant associations, including rs7646596, rs8191981, rs140105250, rs77143352, rs12535759, rs11327184, rs16917546, rs76738175, rs11568075, rs9557175 and rs2801127, with rs7646596 showing the most significant <i>P</i>-value. PRS analysis indicated that individuals with higher polygenic risk scores were significantly more likely to have elevated eosinophil levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified several genetic loci significantly associated with eosinophil levels, highlighting the polygenic nature of eosinophilia. The robust associations, particularly with SNP rs7646596, offer valuable insights into the genetic underpinnings of eosinophilia and related conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals cell immune status and dysregulated monocytes in patients with myasthenia gravis","authors":"Yufan Guo,&nbsp;Yu Gu,&nbsp;Yuting Jin,&nbsp;Xintao Wu,&nbsp;Yuting Lou,&nbsp;Pu Miao,&nbsp;Ye Wang,&nbsp;Bijun Zhang,&nbsp;Xueting Lin,&nbsp;Chudi Zhang,&nbsp;Jianhua Feng","doi":"10.1002/cti2.70052","DOIUrl":"https://doi.org/10.1002/cti2.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>As an autoimmune disorder, myasthenia gravis (MG) manifests as an autoimmune attack on postsynaptic neuromuscular junction proteins by pathogenic autoantibodies. This immune attack disrupts neurotransmission, resulting in fatigable skeletal muscle weakness with diurnal fluctuation. However, functional cure biomarkers for patients remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood collection was performed at three time points in patients with MG: before treatment (Pre), 1 month after treatment (Post) and functional cure (long-term follow-up, LF). Single-cell RNA sequencing was performed. The clinical examination results were collected and summarised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In general, patients with MG exhibited dynamic changes in immune cell composition and inflammatory features. In particular, monocytes were enriched in the LF group, and further subgroup analysis revealed enrichment of CD14⁺S100A12⁺ monocytes and depletion of CD14⁺FOS⁺ monocytes in the LF group. Moreover, inflammation scores were significantly different in the Pre, Post and LF groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides a comprehensive cell landscape for patients with MG, identifies two dysregulated monocytes, elucidates the inflammation status and offers a new perspective on understanding the aetiology of functional cure and potential therapeutic strategies for patients with MG.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}