Clinical immunology最新文献

{"title":"TGF-β1/TRAF-6 and IL-6/STAT-3 pathways in PSA-PSMA phenotypes of hormone-sensitive and hormone-refractory prostate Cancer","authors":"Awatef Ben Jemaa ,&nbsp;Mouna Ben Azaiez ,&nbsp;Sataa Sallami ,&nbsp;Yassine Nouira ,&nbsp;Ezzeddine Ghazouani ,&nbsp;Ridha Oueslati","doi":"10.1016/j.clim.2026.110679","DOIUrl":"10.1016/j.clim.2026.110679","url":null,"abstract":"<div><div>This study explored the relationship between systemic cytokines and PSA–PSMA phenotypes in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), including hormonal therapy response. Serum cytokines (IL-6, TNF-α, IL-10, IL-17 A, TGF-β1) and PSA were quantified, while tissue PSA, PSMA, CD34, TRAF-6, and phosphorylated STAT3 (Ser727, Tyr705) were evaluated immunohistochemically. AR and AR-V7 mRNA expression were assessed by RT-PCR. PCa patients exhibited elevated IL-6 and TGF-β1, higher PSMA and CD34, and reduced tissue PSA compared to BPH. pSTAT3 (Tyr705) increased, whereas pSTAT3 (Ser727) decreased in PCa. In hormone-refractory PCa, TGF-β1 and PSMA were elevated, while PSA declined. AR-V7 was largely absent, and TRAF-6 showed no hormonal difference. These findings suggest IL-6/STAT3 and TGF-β1/TRAF-6 pathways modulate PSA–PSMA dynamics, with TGF-β1/TRAF-6 particularly linked to hormone-refractory progression. Cytokine-mediated signaling may inform PCa diagnosis, prognosis, and therapeutic targeting.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110679"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131298","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":"Relationship between Th1/Th2 balance and medical abortion outcomes in early medical abortion patients","authors":"Ting Feng ,&nbsp;Chaying He ,&nbsp;Yanhua Ding,&nbsp;Wei Huang,&nbsp;Yinghua Li","doi":"10.1016/j.clim.2026.110666","DOIUrl":"10.1016/j.clim.2026.110666","url":null,"abstract":"<div><div>Incomplete abortion is a common complication of medical abortion, potentially related to immune dysregulation. The roles of dendritic cells, Th1/Th2 polarization, and formyl peptide receptor 3 (FPR3) in abortion outcomes are not well understood. We retrospectively analyzed 175 women who underwent early medical abortion between January 2022 and March 2025, classifying them into complete (CA) and incomplete abortion (ICA) groups. A murine model was also used, with mifepristone administered on embryonic days 6.5 to 8.5. FPR3 expression was significantly lower in ICA tissues compared to CA. CA samples showed higher Th1 marker levels and lower Th2 marker levels (all <em>P</em> &lt; 0.001). In mice, mifepristone increased Fpr3 and Tbx21 mRNA levels by 3.5- and 4-fold, respectively, and decreased Gata3 expression by ∼55%. Protein analysis showed similar trends. Mifepristone treatment was accompanied by upregulation of FPR3 and a Th1-biased/Th2-suppressed molecular profile, suggesting a previously unrecognized immune-mediated mechanism that may complement its endocrine effects.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110666"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017406","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":"Single-cell dissection of CD8+ T cell-driven immune dysregulation in type 1 diabetes mellitus: Mechanistic links to diabetic foot pathogenesis","authors":"Pengbo Yang ,&nbsp;Huhe Bao ,&nbsp;Guanwen Sun ,&nbsp;Yaxing Zhang","doi":"10.1016/j.clim.2025.110646","DOIUrl":"10.1016/j.clim.2025.110646","url":null,"abstract":"<div><h3>Background</h3><div>Type 1 diabetes (T1DM) is characterized by autoimmune destruction of pancreatic β-cells and systemic immune dysregulation, yet the cellular networks driving disease progression and their potential link to diabetic complications remain unclear.</div></div><div><h3>Methods</h3><div>We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from 46 stage 3 T1DM patients and 31 matched controls, integrating transcriptomic, cellular interaction, and functional enrichment analyses.</div></div><div><h3>Results</h3><div>Unsupervised clustering of 87,542 cells revealed profound immune dysregulation in T1DM, including cytotoxic CD8+ T cell expansion (70 % increase) and Treg depletion (&gt;50 % reduction). CD8+ T cells exhibited hyperactivation of cytotoxic effectors (GNLY, GZMB) and inflammatory mediators (IL32, S100A4), alongside suppressed regulatory genes (FOXP3, IL2RA). Cell-cell communication analysis identified amplified GALECTIN-CD44 signaling between monocytes/DCs and CD8+ T/NK cells, driving proinflammatory crosstalk. Strikingly, a novel exhausted CD4+ subset (PDCD1+, LAG3+) emerged exclusively in T1DM.</div></div><div><h3>Conclusion</h3><div>Our findings establish CD8+ T cells as central orchestrators of T1DM pathogenesis through synergistic cytotoxic hyperactivity and regulatory collapse. The identified GALECTIN-CD44 axis and JAK-STAT/TGF-β imbalances may extend beyond pancreatic autoimmunity, providing mechanistic insights into systemic complications (e.g., impaired wound healing and chronic inflammation) observed in diabetic patients. These dysregulated networks offer novel therapeutic targets for restoring immune homeostasis in T1DM and its associated comorbidities.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110646"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623447","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":"The dual role of the COX-2/PGE2 Axis in multiple sclerosis: From pathogenesis to pharmacological inhibition","authors":"Ahmed Salem Al-Dhahi ,&nbsp;Hayder M. Al-kuraishy ,&nbsp;Nawar R. Hussain ,&nbsp;Mohamed N. Fawzy ,&nbsp;Mubarak Alruwaili ,&nbsp;Huda J. Waheed ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Ali K. Albuhadily ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.clim.2025.110643","DOIUrl":"10.1016/j.clim.2025.110643","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease of the central nervous system (CNS). The cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) axis plays a complex, dual role in its pathogenesis. Although its upregulation typically induces neuroinflammation, oligodendrocyte apoptosis, and demyelination, certain PGE2 receptors (EP2/EP4) can also mediate protective effects. In experimental models, inhibiting COX-2 (using celecoxib or meloxicam) or blocking pro-inflammatory receptors (EP1/EP3) alleviates disease pathology by reducing immune cell infiltration and cytokine production and protecting oligodendrocytes via both COX-2-dependent and independent mechanisms. This review discusses the potential of selectively targeting the detrimental effects of the COX-2/PGE2 axis (such as EP1/EP3 signaling) while preserving protective pathways as a sophisticated therapeutic strategy for MS. However, cardiovascular risks limit the clinical translation of COX-2 inhibitors, necessitating the development of safer, more precise modulation of this pathway.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110643"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594799","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":"Development and validation of a flow cytometry-based ISG15 induction assay to monitor the type I interferon response","authors":"Birthe Michiels ,&nbsp;Rudi Beyaert ,&nbsp;Jens Staal ,&nbsp;Doreen Dillaerts ,&nbsp;Maaike Cockx ,&nbsp;Glynis Frans ,&nbsp;Birgit Timmermans ,&nbsp;Natalie Lorent ,&nbsp;Isabelle Meyts ,&nbsp;Xavier Bossuyt","doi":"10.1016/j.clim.2025.110654","DOIUrl":"10.1016/j.clim.2025.110654","url":null,"abstract":"<div><div>The type I IFN response plays an important role in the immune defence against invading pathogens and in certain autoinflammatory diseases. In this study, a flow cytometry-based assay to measure ISG15 production in response to stimulation with various TLR ligands and IFNα was developed. PBMCs of healthy controls or patients were stimulated with TLR7/8, TLR3 and TLR9 ligands and IFNα2 whereafter ISG15 expression was measured. The ability of the assay to analyse TLR-dependent type I IFN induction and type I IFN-dependent JAK/STAT activation was verified by inhibition of ISG15 induction by a TBK1/IKKε inhibitor and a JAK1 inhibitor, respectively. TLR7/8 ligand- and TLR9 ligand-induced ISG15 production but not IFNα2-induced ISG15 production was abolished in a patient with AR IRF7 deficiency. IFNα2-induced ISG15 expression was abolished by serum containing neutralizing anti-IFNα2 autoantibodies. The flow cytometry-based ISG15 induction assay can be applied to screen for defects in the type I IFN response.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110654"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676231","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":"Involvement of CCCTC-binding factor (CTCF) in immunomodulation and epigenetic regulation of T helper cell differentiation during Non-Small Cell Lung Cancer (NSCLC)","authors":"Oishi Mukherjee ,&nbsp;Sayani Bose ,&nbsp;Sudeshna Rakshit ,&nbsp;Geetha Shanmugam ,&nbsp;Anuneha Baranwal ,&nbsp;Srawsta Saha ,&nbsp;Harsita Goswami ,&nbsp;Melvin George ,&nbsp;Koustav Sarkar","doi":"10.1016/j.clim.2025.110662","DOIUrl":"10.1016/j.clim.2025.110662","url":null,"abstract":"<div><div>Recent advances in NSCLC therapy remain limited by treatment resistance, much of which is influenced by epigenetic regulation of immune responses. In this study, we investigate the role of CTCF, a chromatin architectural protein that modulates enhancer–promoter interactions, in shaping T-helper (T_H) cell differentiation and tumor immunity. Changes in CTCF expression coincided with altered chromatin-level enrichment patterns involving DNA repair–associated factors (ERCC1, XPF, CSA) and tumor-related proteins at the <em>IFNG</em> locus, as well as shifts in histone modification marks (H3K4me3 and H3K27me3) at T_H1-associated genes, including <em>TBX21</em> and <em>IFNG</em>. These chromatin-associated features were accompanied by increased nitric oxide production and enhanced cytotoxicity in functional assays. Collectively, these findings suggest that variation in CTCF levels is linked to coordinated epigenetic and immune-associated changes in NSCLC, supporting its potential relevance as an immuno-epigenetic factor in shaping anti-tumor immune responses.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110662"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892215","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":"Remaining molecular scarring in the skin of patients with psoriasis: What are the reversal factors?","authors":"Parvaneh Hatami ,&nbsp;Hamed Nicknam Asl ,&nbsp;Zeinab Aryanian ,&nbsp;Azadeh Khayyat ,&nbsp;Mona Homayouni ,&nbsp;Arash Mostaghimi","doi":"10.1016/j.clim.2025.110645","DOIUrl":"10.1016/j.clim.2025.110645","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110645"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623444","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":"Clinical prognosis and cancer risk assessment in autoimmune diseases with anti–TIF1γ alone or concurrent with anti–Ro52 antibodies in a Taiwanese cohort","authors":"Chih-Chun Lee ,&nbsp;Li-Chung Chiu ,&nbsp;Shih-Ching Lee ,&nbsp;Tien-Ming Chan","doi":"10.1016/j.clim.2026.110663","DOIUrl":"10.1016/j.clim.2026.110663","url":null,"abstract":"<div><h3>Objective</h3><div>Dermatomyositis (DM), a subset of idiopathic inflammatory myopathies, affects the skin and skeletal muscles and is associated with an increased cancer risk, particularly in patients with antibodies against transcriptional intermediary factor 1γ (TIF1γ). This study aimed to evaluate the diagnostic value of anti–TIF1γ antibodies and assess their clinical significance, especially regarding cancer risk and associations with other autoimmune diseases (including overlap syndromes).</div></div><div><h3>Methods</h3><div>In this multicenter retrospective study, we identified patients with positive anti–TIF1γ tests from Chang Gung Medical Foundation (2019–2021). Anti–TIF1γ and anti–Ro52 antibodies were detected via line blot and fluorescent enzyme immunoassay. Patients were stratified into strong-positive (++/+++) versus weak-positive (+) groups and analyzed for clinical features and cancer prevalence. Data spanned three full years and were statistically evaluated.</div></div><div><h3>Results</h3><div>Among 84 patients with anti–TIF1γ antibody positivity, 19 (22.6%) were diagnosed with DM, including 15 patients in the strong-positive group and 4 patients in the weak-positive group, and 8 (9.5%) developed malignancy. Strong anti–TIF1γ positivity was significantly linked to dermatomyositis (46.7% vs. 7.4% in weak-positive, <em>p</em> &lt; 0.05) and higher cancer incidence (20.0% vs. 3.7%, <em>p</em> = 0.0221). Moreover, concurrent anti–TIF1γ and anti–Ro52 seropositivity correlated with systemic lupus erythematosus (23.8% vs. 4.8%, <em>p</em> = 0.0211) and SLE–SjS overlap (14.3% vs. 0%, <em>p</em> = 0.0140). Typical skin findings included heliotrope rash, Gottron sign, and periungual telangiectasias; malignancies observed were nasopharyngeal carcinoma and lung cancer in this cohort.</div></div><div><h3>Conclusions</h3><div>High anti-TIF1γ titers significantly increase dermatomyositis and cancer risk. Concomitant anti-Ro52 was associated with SLE and SLE–SjS overlap, emphasizing the necessity of comprehensive myositis antibody profiling for diagnosis and risk assessment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110663"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988592","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":"Single-cell sequencing reveals APOE deletion alleviates adipose wasting in cancer cachexia via macrophage repolarization","authors":"Jun Han ,&nbsp;Qifeng Yao ,&nbsp;Qiuyue Huang ,&nbsp;Zuoyou Ding ,&nbsp;Guohao Wu","doi":"10.1016/j.clim.2025.110660","DOIUrl":"10.1016/j.clim.2025.110660","url":null,"abstract":"<div><div>Cancer cachexia involves severe skeletal muscle and adipose tissue loss. The role of Apolipoprotein E (ApoE) in adipose remodeling remains unclear. This study investigated ApoE's function in cancer cachexia. We found cachectic patients had decreased plasma ApoE but elevated expression in subcutaneous adipose. In vitro, ApoE knockdown in adipocytes downregulated both lipogenesis and lipolysis genes. In vivo, ApoE^−/− mice were protected against adipose wasting in a cachexia model. Single-cell RNA sequencing revealed ApoE deficiency altered immune cell dynamics, increasing total macrophages and enriching a specific Cbr2+ macrophage subpopulation with an M2-like phenotype. This was confirmed by immunofluorescence showing enhanced M2 macrophage infiltration in adipose tissue. We conclude that ApoE is a critical regulator of adipose homeostasis and immune modulation in cancer cachexia, representing a promising diagnostic and therapeutic target.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110660"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836500","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":"A novel diagnostic signature constructed based on serum-circulating m1A-related miRNAs for cancer detection","authors":"Wei Qiu ,&nbsp;Ya Huang ,&nbsp;Yan Gu ,&nbsp;Yichi Sun ,&nbsp;Ping Yue ,&nbsp;KaiDe Xia ,&nbsp;Shichao Zhang","doi":"10.1016/j.clim.2025.110661","DOIUrl":"10.1016/j.clim.2025.110661","url":null,"abstract":"<div><div>Emerging data have revealed that m¹A modification and its regulators are key participants in tumorigenesis and progression. The cell-free miRNAs have been demonstrated to circulate stably in the serum, making them biomarker candidates for cancer diagnosis. Here we included 16,902 serum samples to develop a diagnostic signature named m1A-miRNA signature based on serum circulating m¹A-related miRNAs for cancer detection. The m1A-miRNA signature presented excellent accuracy, and the area under the curve (AUC) was 0.991 in the training cohort. The diagnostic capability of the m1A-miRNA signature was not affected by sexual distinction, age and non-cancer disease. As far as distinguishing cancer types is concerned, the signature exerted superior ability in identifying the types of glioblastoma multiforme, gastric cancer and lung cancer. We also found that the m1A-miRNA signature showed a satisfactory AUC in the early diagnosis of pan-cancer. Additionally, the accuracy of the m1A-miRNA signature was further verified by clinical samples.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110661"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846397","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}