Clinical and Experimental Medicine最新文献

{"title":"Fatty acids metabolic reprogramming and tumor microenvironment in pancreatic cancer: targeting pathways.","authors":"Bassant Ehab, Ekram Saleh","doi":"10.1007/s10238-026-02235-y","DOIUrl":"10.1007/s10238-026-02235-y","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive form of pancreatic cancer. It is distinguished by a profound metabolic plasticity that supports its survival in a hypoxic and nutrient deprived microenvironment. Among the metabolic pathways altered in PDAC, fatty acid metabolism including synthesis, uptake, storage and β-oxidation serves as a key metabolic process that supports tumor growth, progression, and therapeutic resistance. This review discusses emerging evidence on fatty acid metabolic reprogramming and its relevance to the development and progression of pancreatic ductal adenocarcinoma. Key dysregulated enzymes as well as critical metabolic regulators are highlighted. Also, we discuss how genetic alterations drive lipogenic and oxidative pathways to sustain proliferation, redox balance, and adaptation to metabolic stress. Additionally, this review integrates current evidence to illustrate how the tumor microenvironment influences enhancing lipid availability and promoting metabolic symbiosis. Finally, this review outlines current pharmacological approaches that interfere with fatty acid metabolism, emphasizing lipid metabolism as a promising potential intervention strategy to inhibit tumor growth and sensitize cancer cells to existing treatments.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Clonal Metamorphosis: Deconstructing MPN Evolution with Single-Cell and Spatial Multi-Omics.","authors":"Muhammad Shahid Iqbal, Abdullah K Alahmari, Mohd Faiyaz Khan, Sadaf Farooqui, Muhammad Zahid Iqbal, Salah-Ud-Din Khan, Nazia Khan, Vidya Devanathadesikan Seshadri, Amr Ali Mohamed Abdelgawwad El-Sehrawy","doi":"10.1007/s10238-026-02261-w","DOIUrl":"10.1007/s10238-026-02261-w","url":null,"abstract":"","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis identifies KANSL2 as a cell-cycle-associated regulator of tumor progression and immunity in liver hepatocellular carcinoma.","authors":"Nanbin Liu, Kun Li, Junqiao Feng, Shan Wang, Ji Li, Wenbin Yang, Senyang Li, Keping Feng","doi":"10.1007/s10238-026-02264-7","DOIUrl":"10.1007/s10238-026-02264-7","url":null,"abstract":"<p><p>KANSL2, a core component of the NSL histone acetyltransferase complex, has been implicated in tumorigenesis. However, its pan-cancer relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. Multi-omics data from TCGA, GEO, and HPA were integrated to systematically evaluate KANSL2 expression, clinical significance, genomic alterations, and immune associations across cancers. Functional enrichment, immune infiltration analyses, and single-cell transcriptomics were performed. In vitro assays were conducted to validate the biological effects of KANSL2 in LIHC cells. KANSL2 is broadly upregulated across cancers and exhibits strong diagnostic performance. Elevated KANSL2 expression correlates with unfavorable prognosis, particularly in LIHC. Mechanistically, KANSL2 and its co-expressed genes are enriched in cell-cycle progression. KANSL2 expression is also closely associated with immune infiltration and immunoregulatory signaling within the tumor microenvironment, with single-cell data indicating preferential expression in proliferative T-cell subsets. Functional experiments demonstrate that KANSL2 silencing suppresses proliferation, migration, and invasion, and induces G2/M phase arrest in LIHC cells. Notably, its effects on apoptosis are limited, suggesting that KANSL2 primarily drives tumor progression through cell-cycle-dependent mechanisms. This study identifies KANSL2 as a key regulator of tumor progression and immune remodeling in LIHC. By promoting malignancy predominantly via cell-cycle control, KANSL2 represents a promising biomarker for diagnosis and prognosis, and a potential therapeutic target.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extranodal involvement defines distinct immune-molecular phenotypes and clinical outcomes in diffuse large b-cell lymphoma.","authors":"Yiliya Ahongjiang, Lihua Qiu, Min Li, Biwen Sun, Huilai Zhang, Chen Tian","doi":"10.1007/s10238-026-02268-3","DOIUrl":"10.1007/s10238-026-02268-3","url":null,"abstract":"<p><p>Extranodal involvement (ENI) is incorporated into routine risk assessment for diffuse large B-cell lymphoma (DLBCL), but treating ENI as a single binary adverse feature may conceal clinically relevant heterogeneity in extranodal burden, anatomical distribution, treatment feasibility, and immune-molecular context. We evaluated ENI as a burden- and site-aware phenotype rather than as a uniform descriptor. We retrospectively studied 710 adults with newly diagnosed DLBCL treated with first-line immunochemotherapy between June 2011 and December 2024. Outcomes were analyzed according to ENI status, number of extranodal sites, and involved organs. Targeted sequencing was available in 176 tumors, and RNA sequencing was performed in 107 quality-controlled tumor samples. Clinical models were interpreted as adjustment models because ENI burden overlaps with established risk factors; site-specific and molecular analyses were prespecified as exploratory and were interpreted with attention to available-case denominators, treatment heterogeneity, sparse subgroups, and multiplicity. ENI was associated with inferior overall survival (OS) and progression-free survival (PFS) in unadjusted analyses. Multisite ENI was enriched for adverse baseline features, including advanced Ann Arbor stage, elevated lactate dehydrogenase (LDH), higher International Prognostic Index (IPI), and impaired performance status. After multivariable adjustment, the independent prognostic contribution of ENI burden was attenuated, indicating substantial clinical overlap with systemic disease burden and host fitness. Several anatomical sites showed candidate adverse signals, but rare-site estimates were limited by small subgroup sizes, wide confidence intervals, and multiple testing. Targeted sequencing and RNA-seq suggested heterogeneous genomic and immune-transcriptional patterns across ENI categories; these results should be regarded as hypothesis-generating because of tissue availability, tumor-only sequencing in many cases, modest molecular sample sizes, and lack of orthogonal immune validation. ENI in DLBCL is best interpreted as a clinically heterogeneous disease descriptor rather than a single uniform prognostic category. ENI burden and anatomical distribution provide useful descriptive and prognostic context, but they should be interpreted alongside established clinical risk, treatment intensity, censoring patterns, tissue-sampling constraints, and molecular ascertainment limitations. Exploratory genomic and immune-transcriptional correlates identified in this study require prospective multicenter validation with harmonized staging, treatment-intensity annotation, matched-normal sequencing, and spatial or cellular immune profiling before ENI-informed biological or therapeutic stratification can be applied clinically.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint association of physical activity and sedentary time with all-cause and cardiovascular mortality among advanced CKM syndrome participants, insights from NHANES 2007-2018.","authors":"Yuzhe Huang, Quanjun Liu, Shuhua Chen, Hong Xiang, Haijiao Long, Jie Ouyang, Junxi Liao, Shiying Qin, Hongwei Lu","doi":"10.1007/s10238-026-02202-7","DOIUrl":"10.1007/s10238-026-02202-7","url":null,"abstract":"<p><p>Cardiovascular-kidney-metabolic (CKM) syndrome represents the interconnection of metabolic dysfunction, chronic kidney disease, and cardiovascular disease, with advanced stages associated with high mortality. However, the associations of leisure-time physical activity (PA) and sedentary time with mortality in participants with advanced CKM syndrome remain unclear. This study conducted a prospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Multivariate Cox proportional hazards models, restricted cubic spline (RCS) analyses, and subgroup analyses were applied to examine the independent and joint associations of leisure-time PA and sedentary time with all-cause and cardiovascular mortality among participants with advanced CKM syndrome. Among advanced CKM participants, physical inactivity was associated with higher risks of all-cause (HR = 2.43, 95% CI: 1.98-2.97, P < 0.001) and cardiovascular mortality (HR = 2.62, 95% CI: 1.79-3.82, P < 0.001). Compared with < 4 h/day, sedentary time > 8 h/day was independently linked to elevated risks of all-cause (HR = 1.71, 95% CI: 1.33-2.19, P < 0.001) and cardiovascular mortality (HR = 2.12, 95% CI: 1.34-3.38, P = 0.005). Joint analyses showed that the group characterized by physical inactivity combined with ≥ 6 h/day sedentary time was associated with the highest risk of all-cause (HR = 2.77, 95% CI: 2.16-3.56, P < 0.001) and cardiovascular mortality (HR = 3.39, 95% CI: 2.13-5.40, P < 0.001). These associations were further supported by RCS analyses and sensitivity analyses. The findings underscore the potential survival advantages associated with enhancing physical activity and reducing sedentary behavior in this high-risk population.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of IFIT1 and IFIT3 in systemic lupus erythematosus: modeling a diagnosis and exploring immune regulation.","authors":"Luofei Huang, Jian Shi","doi":"10.1007/s10238-026-02265-6","DOIUrl":"10.1007/s10238-026-02265-6","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by multi-organ involvement and a protracted clinical course. Current diagnostic strategies, which rely heavily on clinical symptoms and serology, are often insufficient for early detection. Therefore, highly accurate diagnostic biomarkers are urgently needed to facilitate early intervention and optimize personalized treatment strategies. D atasets GSE61635 and GSE135779 were integrated to identify differentially expressed genes. Weighted gene co-expression network analysis (WGCNA) was performed to isolate the module with the strongest clinical relevance. Mendelian randomization and single‑cell RNA‑seq were used to identify key disease‑relevant genes. A diagnostic model was then constructed, and gene set variation analysis (GSVA), along with gene set enrichment analysis (GSEA), was conducted to elucidate the underlying molecular pathways. IFIT1 and IFIT3 were identified as 2 core genes highly expressed in monocytes and T cells of SLE patients. Functional enrichment analysis revealed that these genes were enriched in immune-related pathways, metabolic pathways related to inflammation and genomic stability. The diagnostic model showed good accuracy, with an area under the curve (AUC) of 0.974 on the training set and 0.912 on the validation set. IFIT1 and IFIT3 represent promising biomarkers for diagnosing SLE and appear to mediate key immune and metabolic disturbances. Furthermore, the developed model serves as an accurate and reliable instrument for early diagnosis and personalized therapy. Large-scale clinical studies are warranted to further validate these findings and evaluate their clinical application.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased group 2 Innate lymphoid cell (ILC2) activity in pediatric familial mediterranean fever patients with spondyloarthropathy.","authors":"Aysenur Pac Kisaarslan, Zehra Busra Azizoglu, Sumeyra Ozdemir Cicek, Busra Seniz Demir, Hakan Poyrazoglu, Ahmet Eken","doi":"10.1007/s10238-026-02260-x","DOIUrl":"https://doi.org/10.1007/s10238-026-02260-x","url":null,"abstract":"<p><p>Familial Mediterranean fever (FMF), an autoinflammatory disease caused by MEFV mutations, frequently coexists with immune-mediated conditions such as spondyloarthritis (SpA). However, the contribution of innate lymphoid cells (ILCs) to FMF-associated SpA remains poorly defined. Our objective was to characterize the phenotype and functional activity of ILCs in pediatric patients with FMF, SpA, and overlap FMF/SpA. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from FMF (n = 15), SpA (n = 11), FMF/SpA (n = 13), and age-matched healthy controls (n = 14) were analyzed by flow cytometry to quantify ILC subsets. Plasma and synovial cytokines were measured by ELISA, and expression of ILC-associated cytokines in PBMCs and sorted ILCs was assessed by quantitative PCR. Total ILC frequencies and subset distributions in PBMCs and SFMCs were comparable across groups (p > 0.05). However, FMF/SpA patients demonstrated increased IL4 and IL5 expression in sorted ILCs (p < 0.05), consistent with a type 2-skewed ILC activation profile. PBMC thymic stromal lymphopoietin (TSLP) expression was elevated in SpA (p < 0.01). Plasma IL-6, IL-8 and IP-10 concentrations were higher in the full cohort of FMF/SpA patients; however, these differences were sensitive to outlier exclusion and indicate substantial inter-individual heterogeneity. Synovial fluid from SpA patients showed higher IP-10 and IL-17 levels (p < 0.05). Pediatric FMF/SpA is characterized by altered ILC functional polarization rather than numerical expansion, with a prominent type 2 ILC signature. In contrast, SpA displays synovial IP-10 and IL-17 enrichment and increased PBMC TSLP expression. These findings suggest distinct innate immune activation axes in overlap versus isolated SpA and support further investigation of ILC-mediated pathways in FMF-associated spondyloarthritis in larger cohorts.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatic evaluation unveils a cellular senescence gene signature as a poor prognostic factor in hepatocellular carcinoma.","authors":"Shaoyang Lu, Junjie Ma, Xiaodan Wang, Lei Zhang, Jin Lu, Junjie Hu","doi":"10.1007/s10238-026-02258-5","DOIUrl":"10.1007/s10238-026-02258-5","url":null,"abstract":"<p><p>Cellular senescence (CS) plays a crucial role in various diseases, but its role in hepatocellular carcinoma (HCC) remains unclear. CS-related genes were clustered to identify subtypes. A risk score was constructed and validated in three independent cohorts. Associations with clinical characteristics, tumor immune microenvironment, mutation status, heterogeneity, and treatment efficacy were analyzed. Single-cell analysis was used to examine risk score distribution, and machine learning algorithms along with a nomogram were applied to assess prognostic value. Three CS subtypes were identified, with subtype 1 showing the worst prognosis. High risk score was associated with advanced clinical stage and grade, poor prognosis, and an immunosuppressive microenvironment driven by regulatory T cells. It also correlated with higher tumor mutations (notably TP53) and increased heterogeneity. High-risk patients showed poor response to sorafenib and transcatheter arterial chemoembolization (TACE) and may benefit less from immunotherapy. At single-cell level, the risk score was predominantly expressed in malignant hepatocytes and linked to cell stemness. The CS-related risk score is a potential prognostic indicator for poor outcomes in HCC, playing a significant role in tumor progression and offering potential value for clinical diagnosis and prediction of treatment response.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immature neutrophil response is associated with cardiac complications after non-traumatic subarachnoid hemorrhage.","authors":"Madeleine M Puissant, Joanne T deKay, Elizabeth K Glisic, Joshua P Passarelli, Angela M Leclerc, Christine Lord, Meghan Searight, Mary S Weatherbee, Lacey Knudsen, Richard R Riker, Teresa L May, David Gagnon, Sergey Ryzhov, David B Seder","doi":"10.1007/s10238-026-02262-9","DOIUrl":"10.1007/s10238-026-02262-9","url":null,"abstract":"<p><p>Acute non-traumatic subarachnoid hemorrhage (SAH) is complicated by systemic inflammation and cardiac dysfunction that contribute to the high rates of morbidity and mortality. To better define the mechanistic relationship between immune response and cardiac complications, we evaluated subpopulations of circulating immune cells and their associations with abnormalities of cardiac rhythm, injury biomarkers, and mechanical function after hemorrhage. In this single-site prospective observational study, we screened all adult patients presenting to our neurocritical care unit with non-traumatic SAH who required external ventricular drain (EVD) placement for treatment of hydrocephalus. Following informed consent, peripheral blood samples were obtained at post-bleed days (PBDs) 1, 3, 5, 7, and 10. Subjects were separated into groups based on evidence of cardiac abnormalities (cAbn(+))\" versus \"no cardiac abnormalities (cAbn(-)),\" and flow cytometric analysis was used to identify and quantify immune cell subpopulations. Circulating neutrophil-secreted factors, including myeloperoxidase (MPO), were measured in plasma using ELISA. We measured associations between these immune factors and cardiac abnormalities. Sixty patients were enrolled between January 2018 and August 2023. Our patient cohort was 65% female with a median age of 58 (IQR 51-68). Poor grade SAH (Hunt Hess = 4-5) occurred in 52% (n = 31) of patients. In the overall cohort 47 (78%) required prolonged mechanical ventilation (> 24-hours), and 52 (87%) underwent coil embolization/clipping of their aneurysm. The average ICU and hospital lengths of stay (LOS) were 18.5 (IQR 12.2-22) and 23 (IQR 18.2-33.8) days, respectively. In-hospital mortality for enrolled patients was 11.8% and overall mortality 6 months after discharge was 25% (n = 15). 40% (n = 24) of patients were discharged home, 37% (n = 22) to acute rehabilitation, 8% (n = 5) to SNF, and 3% (n = 2) to hospice. Cardiac abnormalities after SAH were associated with increased circulating neutrophil counts but not monocyte or lymphocyte levels. Circulating neutrophils in patients with cardiac abnormalities also had reduced cell-surface expression of maturation markers CD10, CD14, and CD16 in patients with cardiac abnormalities. Elevated levels of immature neutrophils and circulating levels of lipocalin-2, and myeloperoxidase (MPO) correlated with increased Hunt-Hess score, ICU, and hospital length of stay. Higher grade SAH was associated with increased immature neutrophil response, which was associated with cardiac abnormalities. These cardiac abnormalities tracked with increased levels of pro-inflammatory lipocalin-2 and MPO, and worse outcomes.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of VISTA on peripheral blood mononuclear cells in Systemic lupus erythematosus: association with disease activity and treatment status.","authors":"Afsaneh Enteshari-Moghaddam, Rozita Abolhasan, Meysam Motevasseli, Nasrin Fouladi, Majid Eterafi, Sahar Samemaleki, Hamed Kyanfar, Elham Safarzadeh","doi":"10.1007/s10238-026-02254-9","DOIUrl":"10.1007/s10238-026-02254-9","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and multi-organ involvement due to dysregulated immune responses. Ongoing research aims to understand the underlying mechanisms of this immune dysregulation, with particular interest in immune checkpoint molecules such as VISTA (encoded by the VSIR gene), which exerts context-dependent immunomodulatory effects. We analyzed a large-scale single-cell RNA-seq (scRNA-seq) dataset (GSE174188) comprising 261 samples (162 SLE cases, 99 controls) to investigate VSIR expression patterns across peripheral blood mononuclear cell (PBMC) subsets in SLE versus controls, using bioinformatics tools. Additionally, fresh PBMCs were isolated from SLE patients and healthy controls, and VSIR mRNA levels were quantified by RT-qPCR in treatment-naïve cases and those receiving Prednisolone, Hydroxychloroquine, or supplementary medications. Associations between VSIR expression and clinical/demographic parameters, including disease activity index, were also evaluated. scRNA-seq analysis revealed significantly upregulated VSIR expression in monocytes from SLE patients compared to healthy controls. In contrast, pseudobulk differential expression analysis of the entire PBMC population, corroborated by RT-qPCR on fresh samples, demonstrated downregulation of VSIR in SLE cases overall (log₂ fold change = -1.23). Notably, VSIR expression differed across treatment groups, with the lowest levels observed in treatment-naïve patients and higher levels in those receiving first-line therapies (prednisolone and hydroxychloroquine). Furthermore, VSIR expression exhibited a significant negative correlation with SLE disease activity index. This study demonstrates decreased VSIR expression in the whole PBMC population in SLE patients, suggesting a potential role in disease pathogenesis processes possibly through altered immune checkpoint regulation. Moreover, VSIR expression was associated with treatment status, with higher expression observed in patients receiving standard first-line therapies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}