Pub Date : 2026-04-01Epub Date: 2026-02-08DOI: 10.1016/j.clim.2026.110680
Yuhan Li , Songcheng Ying
Aicardi-Goutières Syndrome (AGS) is a rare monogenic autoinflammatory disorder primarily affecting the central nervous system. It is characterized by elevated levels of type I interferon (IFN-I) in the cerebrospinal fluid. Mutations in SAMHD1 gene cause AGS type 5. The primary function of SAMHD1 is to maintain genome stability by regulating the dNTP pool through its enzymatic activity. This review comprehensively describes the role of loss-of-function mutations in SAMHD1 in the pathogenesis of AGS. It covers the molecular structure and function of SAMHD1, as well as its relationship with type I interferon responses. We explore potential mechanisms by which SAMHD1 mutations lead to AGS, including the accumulation of DNA damage, upregulation of LINE-1 reverse transcription, and abnormal RNA metabolism. Additionally, we summarize current research progress, therapeutic challenges, and future directions for AGS. A deeper understanding of SAMHD1 function may lead to new strategies for diagnosing and treating SAMHD1-mutation-associated AGS.
{"title":"Aicardi-Goutières Syndrome caused by SAMHD1 mutation: Pathogenesis and Beyond","authors":"Yuhan Li , Songcheng Ying","doi":"10.1016/j.clim.2026.110680","DOIUrl":"10.1016/j.clim.2026.110680","url":null,"abstract":"<div><div>Aicardi-Goutières Syndrome (AGS) is a rare monogenic autoinflammatory disorder primarily affecting the central nervous system. It is characterized by elevated levels of type I interferon (IFN-I) in the cerebrospinal fluid. Mutations in SAMHD1 gene cause AGS type 5. The primary function of SAMHD1 is to maintain genome stability by regulating the dNTP pool through its enzymatic activity. This review comprehensively describes the role of loss-of-function mutations in SAMHD1 in the pathogenesis of AGS. It covers the molecular structure and function of SAMHD1, as well as its relationship with type I interferon responses. We explore potential mechanisms by which SAMHD1 mutations lead to AGS, including the accumulation of DNA damage, upregulation of LINE-1 reverse transcription, and abnormal RNA metabolism. Additionally, we summarize current research progress, therapeutic challenges, and future directions for AGS. A deeper understanding of SAMHD1 function may lead to new strategies for diagnosing and treating SAMHD1-mutation-associated AGS.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110680"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156402","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}
Pub Date : 2026-04-01Epub Date: 2026-02-03DOI: 10.1016/j.clim.2026.110678
Qianwei Zhao , Ludan Zhang , Peiqi Yu , Jingjing Liu , Tingjiang He , Yunhui Qu , Anqi Cheng , Fang Xu , Liping Dai
Background
Tumor-associated autoantibodies (TAAbs) represent promising biomarkers for tumor diagnosis. This study aimed to evaluate the prognostic value of anti- Dihydrolipoamide S-acetyltransferase (DLAT) AAb in breast cancer (BC).
Methods
Levels of plasma anti-DLAT AAb were measured by ELISA in a total of 1013 samples from BC patients, patients with benign breast nodules (BN), and healthy controls (NC). Western blot was performed to confirm the ELISA results. The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were used to analyze the expression levels of DLAT in tumor and normal breast tissues from BC patients.
Results
Plasma anti-DLAT AAb levels were decreased in BC compared to NC and BN, achieving AUCs of 0.803 (P < 0.0001) and 0.591 (P < 0.0001), respectively. Among individuals under 45 years old, anti-DLAT AAb showed high power in distinguishing BC and BC at early-stage from NC, yielding an AUC of 0.873 (P < 0.0001) and 0.845 (P < 0.0001). Besides, anti-DLAT AAb distinguished BC from BN with an AUC of 0.617 (P = 0.0016) in individuals under 45 while there was no difference between them above 45. Combining anti-DLAT AAb with CEA improved the AUCs to 0.824 (P < 0.0001) and 0.623 (P < 0.0001) for distinguishing BC from NC and BN. This combination also achieved higher AUCs of 0.891 (P < 0.0001) and 0.635 (P = 0.0003) for distinguishing BC from NC and BN among individuals under 45 years old.
Conclusions
These findings suggest that anti-DLAT AAb shows potential for BC diagnosis, especially among individuals under 45 years old. Besides, multicenter validation should be carried out to confirm this finding in the future.
{"title":"Plasma anti-DLAT autoantibody as a novel diagnostic biomarker in breast cancer","authors":"Qianwei Zhao , Ludan Zhang , Peiqi Yu , Jingjing Liu , Tingjiang He , Yunhui Qu , Anqi Cheng , Fang Xu , Liping Dai","doi":"10.1016/j.clim.2026.110678","DOIUrl":"10.1016/j.clim.2026.110678","url":null,"abstract":"<div><h3>Background</h3><div>Tumor-associated autoantibodies (TAAbs) represent promising biomarkers for tumor diagnosis. This study aimed to evaluate the prognostic value of anti- Dihydrolipoamide <em>S</em>-acetyltransferase (DLAT) AAb in breast cancer (BC).</div></div><div><h3>Methods</h3><div>Levels of plasma anti-DLAT AAb were measured by ELISA in a total of 1013 samples from BC patients, patients with benign breast nodules (BN), and healthy controls (NC). Western blot was performed to confirm the ELISA results. The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were used to analyze the expression levels of DLAT in tumor and normal breast tissues from BC patients.</div></div><div><h3>Results</h3><div>Plasma anti-DLAT AAb levels were decreased in BC compared to NC and BN, achieving AUCs of 0.803 (<em>P</em> < 0.0001) and 0.591 (<em>P</em> < 0.0001), respectively. Among individuals under 45 years old, anti-DLAT AAb showed high power in distinguishing BC and BC at early-stage from NC, yielding an AUC of 0.873 (<em>P</em> < 0.0001) and 0.845 (<em>P</em> < 0.0001). Besides, anti-DLAT AAb distinguished BC from BN with an AUC of 0.617 (<em>P</em> = 0.0016) in individuals under 45 while there was no difference between them above 45. Combining anti-DLAT AAb with CEA improved the AUCs to 0.824 (<em>P</em> < 0.0001) and 0.623 (<em>P</em> < 0.0001) for distinguishing BC from NC and BN. This combination also achieved higher AUCs of 0.891 (<em>P</em> < 0.0001) and 0.635 (<em>P</em> = 0.0003) for distinguishing BC from NC and BN among individuals under 45 years old.</div></div><div><h3>Conclusions</h3><div>These findings suggest that anti-DLAT AAb shows potential for BC diagnosis, especially among individuals under 45 years old. Besides, multicenter validation should be carried out to confirm this finding in the future.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110678"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123692","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}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.clim.2026.110667
Jinkai Liang , Jiaqi Wang , Hui Fang , Xin Tang, Ke Xue, Wanting Liu, Shuai Shao, Gang Wang
Neutrophils are key components of the innate immune system, rapidly migrating to sites of infection or inflammation to perform bactericidal functions. Their lifespan is short, spanning from development and circulation to migration, aging, and eventual death. Neutrophil death plays a critical role in both physiological and pathological processes. This review explores the different death mechanisms of neutrophils, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and discusses their implications in immune-mediated inflammatory diseases (IMIDs). This review examines the connection between neutrophil metabolism and cell death, as well as potential interactions among these death pathways. A clearer understanding of these death mechanisms in the context of immune diseases can enhance our comprehension of disease pathogenesis and inform the development of targeted therapeutic strategies.
{"title":"Life towards death: Neutrophils in immune-mediated inflammatory diseases","authors":"Jinkai Liang , Jiaqi Wang , Hui Fang , Xin Tang, Ke Xue, Wanting Liu, Shuai Shao, Gang Wang","doi":"10.1016/j.clim.2026.110667","DOIUrl":"10.1016/j.clim.2026.110667","url":null,"abstract":"<div><div>Neutrophils are key components of the innate immune system, rapidly migrating to sites of infection or inflammation to perform bactericidal functions. Their lifespan is short, spanning from development and circulation to migration, aging, and eventual death. Neutrophil death plays a critical role in both physiological and pathological processes. This review explores the different death mechanisms of neutrophils, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and discusses their implications in immune-mediated inflammatory diseases (IMIDs). This review examines the connection between neutrophil metabolism and cell death, as well as potential interactions among these death pathways. A clearer understanding of these death mechanisms in the context of immune diseases can enhance our comprehension of disease pathogenesis and inform the development of targeted therapeutic strategies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110667"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017429","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}
Pub Date : 2026-04-01Epub Date: 2026-02-02DOI: 10.1016/j.clim.2026.110676
Susanna Scaglioni , Andrea Lombardi , Giacomo M. Butta , Giorgio Bozzi , Matteo Centazzo , Bianca Mariani , Antonio Muscatello , Patrizia Bono , Lorena Donnici , Matteo Conti , Riccardo Nodari , Annapaola Callegaro , Edoardo Scarpa , Renata Grifantini , Sergio Abrignani , Raffaele De Francesco , Andrea Gori , Alessandra Bandera , Lara Manganaro
Vaccination triggers both humoral and cellular immune responses, generating memory T cells that ensure long-term protection. Among these, stem cell-like memory T cells (TSCM) are crucial for durable immunity due to their self-renewal and multipotency. In people with HIV (PWHIV), vaccine-induced responses can be weakened by persistent immune dysfunction. In this study, we longitudinally analyzed T cell memory responses following mRNA-1273 vaccination in PWHIV. Individuals with incomplete immune reconstitution (CD4+ < 500 cells/μL, CD4/CD8 < 0.4) showed reduced frequencies of Spike-specific CD4+ TSCM, lower levels of TCF-1 and higher expression of immune checkpoint molecules. We identified a subset of PD-1+TIGIT+ CD4+ TSCM and TCM cells that phenotypically resemble CD8+ exhausted-like progenitors (TPEX) and are enriched in PWHIV with poor immune recovery. Modulation of the Wnt/mTORs pathway via GSK3β inhibition restored TCF-1 expression and partially rescued antigen responsiveness, highlighting a potential strategy to improve vaccine efficacy in PWHIV.
{"title":"HIV patients with poor immune recovery show exhausted CD4+ stem cell memory cells and impaired COVID-19 vaccine response","authors":"Susanna Scaglioni , Andrea Lombardi , Giacomo M. Butta , Giorgio Bozzi , Matteo Centazzo , Bianca Mariani , Antonio Muscatello , Patrizia Bono , Lorena Donnici , Matteo Conti , Riccardo Nodari , Annapaola Callegaro , Edoardo Scarpa , Renata Grifantini , Sergio Abrignani , Raffaele De Francesco , Andrea Gori , Alessandra Bandera , Lara Manganaro","doi":"10.1016/j.clim.2026.110676","DOIUrl":"10.1016/j.clim.2026.110676","url":null,"abstract":"<div><div>Vaccination triggers both humoral and cellular immune responses, generating memory T cells that ensure long-term protection. Among these, stem cell-like memory T cells (T<sub>SCM</sub>) are crucial for durable immunity due to their self-renewal and multipotency. In people with HIV (PWHIV), vaccine-induced responses can be weakened by persistent immune dysfunction. In this study, we longitudinally analyzed T cell memory responses following mRNA-1273 vaccination in PWHIV. Individuals with incomplete immune reconstitution (CD4<sup>+</sup> < 500 cells/μL, CD4/CD8 < 0.4) showed reduced frequencies of Spike-specific CD4<sup>+</sup> T<sub>SCM</sub>, lower levels of TCF-1 and higher expression of immune checkpoint molecules. We identified a subset of PD-1<sup>+</sup>TIGIT<sup>+</sup> CD4<sup>+</sup> T<sub>SCM</sub> and T<sub>CM</sub> cells that phenotypically resemble CD8<sup>+</sup> exhausted-like progenitors (T<sub>PEX</sub>) and are enriched in PWHIV with poor immune recovery. Modulation of the Wnt/mTORs pathway via GSK3β inhibition restored TCF-1 expression and partially rescued antigen responsiveness, highlighting a potential strategy to improve vaccine efficacy in PWHIV.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110676"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118084","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}
Pub Date : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.clim.2026.110665
Afshin Derakhshani , Roberta Di Fonte , Letizia Porcelli , Fatemeh Nejadi Orang , Mahdi Abdoli Shadbad , Adib Miraki Feriz , Hossein Safarpour , Antoine Dufour , Behzad Baradaran , Angela Calabrese , Mario Testini , Riccardo Memeo , Giovanna Di Meo , Leonardo Vincenti , Sonali Bhardwaj , Vito Racanelli , Nicola Silvestris , Oronzo Brunetti , Amalia Azzariti
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, underscoring the need for minimally invasive biomarkers to support patient stratification and disease monitoring. In this study, we aimed to identify PDAC-associated immune signatures by reanalyzing a single-cell RNA-sequencing dataset and to validate key findings using flow cytometry in an independent cohort predominantly composed of advanced-stage PDAC. Analysis of peripheral blood mononuclear cells from patients with PDAC and healthy donors revealed increased expression of S100A6, S100A8, and S100A12, particularly within monocytes and dendritic cells. These transcriptional changes were confirmed at the protein level, demonstrating enrichment of S100A6+ monocytes, S100A6+/S100A8+ DCs, activated monocytes, and plasmacytoid DCs in PDAC. Univariate ROC analyses identified S100A6+ plasmacytoid DCs, S100A8+ plasmacytoid DCs, and CD14+CD86+S100A8+ monocytes as candidate PDAC-associated immune features. However, further validation incorporating benign pancreatic conditions and multivariable modeling is required before conclusions can be drawn regarding diagnostic specificity and clinical applicability.
{"title":"Integrated single cell RNA sequencing and flow cytometry analysis identifies elevated S100A6+ and S100A8+ myeloid subsets in pancreatic ductal adenocarcinoma","authors":"Afshin Derakhshani , Roberta Di Fonte , Letizia Porcelli , Fatemeh Nejadi Orang , Mahdi Abdoli Shadbad , Adib Miraki Feriz , Hossein Safarpour , Antoine Dufour , Behzad Baradaran , Angela Calabrese , Mario Testini , Riccardo Memeo , Giovanna Di Meo , Leonardo Vincenti , Sonali Bhardwaj , Vito Racanelli , Nicola Silvestris , Oronzo Brunetti , Amalia Azzariti","doi":"10.1016/j.clim.2026.110665","DOIUrl":"10.1016/j.clim.2026.110665","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, underscoring the need for minimally invasive biomarkers to support patient stratification and disease monitoring. In this study, we aimed to identify PDAC-associated immune signatures by reanalyzing a single-cell RNA-sequencing dataset and to validate key findings using flow cytometry in an independent cohort predominantly composed of advanced-stage PDAC. Analysis of peripheral blood mononuclear cells from patients with PDAC and healthy donors revealed increased expression of S100A6, S100A8, and S100A12, particularly within monocytes and dendritic cells. These transcriptional changes were confirmed at the protein level, demonstrating enrichment of S100A6<sup>+</sup> monocytes, S100A6<sup>+</sup>/S100A8<sup>+</sup> DCs, activated monocytes, and plasmacytoid DCs in PDAC. Univariate ROC analyses identified S100A6<sup>+</sup> plasmacytoid DCs, S100A8<sup>+</sup> plasmacytoid DCs, and CD14<sup>+</sup>CD86<sup>+</sup>S100A8<sup>+</sup> monocytes as candidate PDAC-associated immune features. However, further validation incorporating benign pancreatic conditions and multivariable modeling is required before conclusions can be drawn regarding diagnostic specificity and clinical applicability.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110665"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040531","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}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.clim.2026.110664
Yiyang Wu , Jintian Wang , Pengcheng Wang , Qiwei Chen , Jing Jia , Yan Liu , Yao Chen , Kai Ye
Background
Microsatellite-stable colorectal cancer (MSS CRC) resists immune checkpoint inhibitors. FGF19's immunomodulatory role in MSS CRC remains unclear.
Methods
Bioinformatics analyzed FGF19 expression and CD8+ T-cell infiltration. CRC cells co-cultured with neutrophils (dHL-60) assessed chemotaxis and NET markers. LDH assay, ELISA, and CFSE staining measured CD8+ T-cell activity. CCK-8, EdU, Transwell, and flow cytometry assessed CRC phenotypes. Mouse model tested PD-1 antibody and FGFR4 inhibitor BLU-9931.
Results
FGF19 was upregulated in non-immunogenic MSS CRC, negatively correlating with CD8+ T cells. Elevated FGF19 enhanced neutrophil chemotaxis and NET release, inhibiting CD8+ T-cell cytotoxicity and proliferation while promoting malignant CRC behavior. Mechanistically, FGF19-FGFR4 signaling was associated with increased ERK pathway activity, elevated IL-8 levels, and NET formation. Blocking FGF19-FGFR4 enhanced PD-1 efficacy in MSS CRC.
Conclusion
The FGF19/ERK/IL-8 pathway contributed to NET formation in this model. Targeting this pathway represents a promising strategy to boost immunotherapy in MSS CRC.
{"title":"Inhibition of neutrophil extracellular traps via the FGF19/ERK/IL-8 axis enhances immune therapy in MSS colorectal cancer","authors":"Yiyang Wu , Jintian Wang , Pengcheng Wang , Qiwei Chen , Jing Jia , Yan Liu , Yao Chen , Kai Ye","doi":"10.1016/j.clim.2026.110664","DOIUrl":"10.1016/j.clim.2026.110664","url":null,"abstract":"<div><h3>Background</h3><div>Microsatellite-stable colorectal cancer (MSS CRC) resists immune checkpoint inhibitors. FGF19's immunomodulatory role in MSS CRC remains unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analyzed FGF19 expression and CD8<sup>+</sup> T-cell infiltration. CRC cells co-cultured with neutrophils (dHL-60) assessed chemotaxis and NET markers. LDH assay, ELISA, and CFSE staining measured CD8<sup>+</sup> T-cell activity. CCK-8, EdU, Transwell, and flow cytometry assessed CRC phenotypes. Mouse model tested PD-1 antibody and FGFR4 inhibitor BLU-9931.</div></div><div><h3>Results</h3><div>FGF19 was upregulated in non-immunogenic MSS CRC, negatively correlating with CD8<sup>+</sup> T cells. Elevated FGF19 enhanced neutrophil chemotaxis and NET release, inhibiting CD8<sup>+</sup> T-cell cytotoxicity and proliferation while promoting malignant CRC behavior. Mechanistically, FGF19-FGFR4 signaling was associated with increased ERK pathway activity, elevated IL-8 levels, and NET formation. Blocking FGF19-FGFR4 enhanced PD-1 efficacy in MSS CRC.</div></div><div><h3>Conclusion</h3><div>The FGF19/ERK/IL-8 pathway contributed to NET formation in this model. Targeting this pathway represents a promising strategy to boost immunotherapy in MSS CRC.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110664"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017493","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}
Pub Date : 2026-04-01Epub Date: 2026-02-02DOI: 10.1016/j.clim.2026.110677
Shu-Zhen Xu , Sha-Sha Tao , Peng Wang , Hai-Fen Wei , Yu-Tong Tan , Jian Tang , Zhu Chen , Hai-Feng Pan
Asprosin, a recently identified adipokine involved in metabolic and inflammatory processes. The case-control study was conducted to explore how asprosin is involved in the pathogenesis of rheumatoid arthritis (RA). 205 RA patients and 205 healthy controls were included, and MH7A cells were used for in vitro studies. Plasma asprosin was elevated in RA patients [11.4 (8.2, 15.6) ng/mL] compared to healthy controls [9.3 (7.5, 10.5) ng/mL] (Z = 5.978, P < 0.001) and exhibited moderate diagnostic accuracy (AUC = 0.67). Asprosin significantly enhanced the proliferation of synovial fibroblasts and upregulated the proinflammatory cytokines, while promoting their migratory and invasive capacities. TNF-α led to a marked downregulation of PPAR-γ, which was associated with increased asprosin levels, treatment with rosiglitazone effectively attenuated asprosin overproduction. Elevated circulating asprosin levels serve as an independent risk factor for RA and demonstrate promising diagnostic potential. PPAR-γ-mediated overexpression of asprosin contributes to synovial fibroblast dysfunction, suggesting a pathogenic role in RA development.
Asprosin，一种最近发现的脂肪因子，参与代谢和炎症过程。本病例对照研究旨在探讨asprosin如何参与类风湿关节炎（RA）的发病机制。纳入205名RA患者和205名健康对照者，并使用MH7A细胞进行体外研究。与健康对照组相比，RA患者血浆asprosin升高[11.4 (8.2,15.6)ng/mL] [9.3 (7.5, 10.5) ng/mL] (Z = 5.978，P
{"title":"Elevated asprosin expression exacerbates synovial inflammation by PPAR-γ-dependent mechanisms in rheumatoid arthritis","authors":"Shu-Zhen Xu , Sha-Sha Tao , Peng Wang , Hai-Fen Wei , Yu-Tong Tan , Jian Tang , Zhu Chen , Hai-Feng Pan","doi":"10.1016/j.clim.2026.110677","DOIUrl":"10.1016/j.clim.2026.110677","url":null,"abstract":"<div><div>Asprosin, a recently identified adipokine involved in metabolic and inflammatory processes. The case-control study was conducted to explore how asprosin is involved in the pathogenesis of rheumatoid arthritis (RA). 205 RA patients and 205 healthy controls were included, and MH7A cells were used for <em>in vitro</em> studies. Plasma asprosin was elevated in RA patients [11.4 (8.2, 15.6) ng/mL] compared to healthy controls [9.3 (7.5, 10.5) ng/mL] (<em>Z</em> = 5.978, <em>P</em> < 0.001) and exhibited moderate diagnostic accuracy (AUC = 0.67). Asprosin significantly enhanced the proliferation of synovial fibroblasts and upregulated the proinflammatory cytokines, while promoting their migratory and invasive capacities. TNF-α led to a marked downregulation of PPAR-γ, which was associated with increased asprosin levels, treatment with rosiglitazone effectively attenuated asprosin overproduction. Elevated circulating asprosin levels serve as an independent risk factor for RA and demonstrate promising diagnostic potential. PPAR-γ-mediated overexpression of asprosin contributes to synovial fibroblast dysfunction, suggesting a pathogenic role in RA development.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110677"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118107","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}
Pub Date : 2026-04-01Epub Date: 2026-02-04DOI: 10.1016/j.clim.2026.110679
Awatef Ben Jemaa , Mouna Ben Azaiez , Sataa Sallami , Yassine Nouira , Ezzeddine Ghazouani , Ridha Oueslati
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.
{"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 , Mouna Ben Azaiez , Sataa Sallami , Yassine Nouira , Ezzeddine Ghazouani , 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}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.clim.2026.110666
Ting Feng , Chaying He , Yanhua Ding, Wei Huang, Yinghua Li
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 P < 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.
{"title":"Relationship between Th1/Th2 balance and medical abortion outcomes in early medical abortion patients","authors":"Ting Feng , Chaying He , Yanhua Ding, Wei Huang, 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> < 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}
Pub Date : 2026-03-19DOI: 10.1016/j.clim.2026.110701
Mahd Rauf, Ahsan Naveed, Muhammad Umer Asghar
Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC.
{"title":"Post-acute sequelae of COVID-19: A disorder of impaired innate immune resolution - A narrative review.","authors":"Mahd Rauf, Ahsan Naveed, Muhammad Umer Asghar","doi":"10.1016/j.clim.2026.110701","DOIUrl":"10.1016/j.clim.2026.110701","url":null,"abstract":"<p><p>Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110701"},"PeriodicalIF":3.8,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493581","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}
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