Pub Date : 2025-10-01Epub Date: 2025-06-24DOI: 10.1016/j.clim.2025.110550
Shaowei Pan , Xiaoyun Xie , Tong Li , Shiyao Wu , Ying Jiang , Huali Zhang , Xiaoli Zhang
Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.
{"title":"IL-33 regulates abnormally increased expression of ST2 in bone marrow follicular helper T cell in SLE with hematological abnormalities","authors":"Shaowei Pan , Xiaoyun Xie , Tong Li , Shiyao Wu , Ying Jiang , Huali Zhang , Xiaoli Zhang","doi":"10.1016/j.clim.2025.110550","DOIUrl":"10.1016/j.clim.2025.110550","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110550"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505039","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 : 2025-10-01Epub Date: 2025-07-23DOI: 10.1016/j.clim.2025.110572
Junhan Wu , Zhe He , Weitao Zhuang , Xin Xia , Zijie Li , Aotian Mo , Yizhang Chen , Rixin Chen , Guibin Qiao
Chronic inflammation is a crucial factor in the development and progression of lung cancer. External factors, such as indoor and outdoor air pollution and occupational hazards, along with imbalances in the lung microbiome, create a pro-inflammatory environment conducive to tumorigenesis. This review explores how various mechanisms drive the production of pro-inflammatory cytokines and immune modulators, leading to a tumor-promoting microenvironment. It also examines the roles of key cells in these processes and highlights the importance of epigenetic modifications in inflammation-driven lung cancer. Understanding these interactions provides insights into targeted therapeutic strategies and underscores the significance of addressing inflammation to reduce lung cancer risk.
{"title":"Mechanisms of inflammation-driven lung cancer: From external influences to internal regulation","authors":"Junhan Wu , Zhe He , Weitao Zhuang , Xin Xia , Zijie Li , Aotian Mo , Yizhang Chen , Rixin Chen , Guibin Qiao","doi":"10.1016/j.clim.2025.110572","DOIUrl":"10.1016/j.clim.2025.110572","url":null,"abstract":"<div><div>Chronic inflammation is a crucial factor in the development and progression of lung cancer. External factors, such as indoor and outdoor air pollution and occupational hazards, along with imbalances in the lung microbiome, create a pro-inflammatory environment conducive to tumorigenesis. This review explores how various mechanisms drive the production of pro-inflammatory cytokines and immune modulators, leading to a tumor-promoting microenvironment. It also examines the roles of key cells in these processes and highlights the importance of epigenetic modifications in inflammation-driven lung cancer. Understanding these interactions provides insights into targeted therapeutic strategies and underscores the significance of addressing inflammation to reduce lung cancer risk.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110572"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717678","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 : 2025-10-01Epub Date: 2025-06-15DOI: 10.1016/j.clim.2025.110540
Valentina Natoli , Amandine Charras , Megan S.R. Hasoon , Andrea L. Jorgensen , Eve M.D. Smith , Eva Caamaño Gutiérrez , Michael W. Beresford , Christian M. Hedrich
Juvenile-onset systemic lupus erythematosus (jSLE) is a complex autoimmune/inflammatory disease in which genetic factors likely contribute to pathophysiology and clinical expression. This study explored associations between general (alternate allele counts; AAC) and gene-specific (alternate allele scores; GAAS) sequence variability, age at onset, sex, ancestry, disease activity/severity, organ involvement and treatments in jSLE. 289 participants from the UK JSLE Cohort Study underwent panel sequencing of 62 genes/genomic regions. Weighted AAC and GAAS were calculated. Correlation analyses and generalized linear models assessed associations between genetic burden, ancestry, age at diagnosis and clinical variables. AAC inversely correlated with age at diagnosis (R = -0.15, p = 0.01), primarily driven by South Asians (R = -0.28, p < 0.001). African/Caribbean patients exhibited higher AAC (p < 0.001). Clinical variables, including severity of renal involvement (ACP5, ITGAM, LYN, p < 0.001; TNFAIP3, p = 0.007), associated with GAAS. Genetic variability likely contributes to early disease expression and severity in jSLE, supporting patient stratification and personalised care.
{"title":"Genetic variability associates with ancestry, age at disease onset, organ involvement and disease severity in juvenile-onset systemic lupus erythematosus","authors":"Valentina Natoli , Amandine Charras , Megan S.R. Hasoon , Andrea L. Jorgensen , Eve M.D. Smith , Eva Caamaño Gutiérrez , Michael W. Beresford , Christian M. Hedrich","doi":"10.1016/j.clim.2025.110540","DOIUrl":"10.1016/j.clim.2025.110540","url":null,"abstract":"<div><div>Juvenile-onset systemic lupus erythematosus (jSLE) is a complex autoimmune/inflammatory disease in which genetic factors likely contribute to pathophysiology and clinical expression. This study explored associations between general (alternate allele counts; AAC) and gene-specific (alternate allele scores; GAAS) sequence variability, age at onset, sex, ancestry, disease activity/severity, organ involvement and treatments in jSLE. 289 participants from the UK JSLE Cohort Study underwent panel sequencing of 62 genes/genomic regions. Weighted AAC and GAAS were calculated. Correlation analyses and generalized linear models assessed associations between genetic burden, ancestry, age at diagnosis and clinical variables. AAC inversely correlated with age at diagnosis (R = -0.15, <em>p</em> = 0.01), primarily driven by South Asians (R = -0.28, <em>p</em> < 0.001). African/Caribbean patients exhibited higher AAC (p < 0.001). Clinical variables, including severity of renal involvement (<em>ACP5</em>, <em>ITGAM</em>, <em>LYN</em>, p < 0.001; <em>TNFAIP3</em>, <em>p</em> = 0.007), associated with GAAS. Genetic variability likely contributes to early disease expression and severity in jSLE, supporting patient stratification and personalised care.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110540"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316037","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 : 2025-10-01Epub Date: 2025-06-24DOI: 10.1016/j.clim.2025.110549
Nabil Belfeki , Nouha Ghriss , Alexandre Le Joncour , David Saadoun
Behçet's disease (BD) is a chronic, multisystemic inflammatory vasculitis affecting veins and arteries. Its etiopathogenesis remains unclear but is thought to result from genetic predisposition combined with environmental triggers. Recent genome-wide association studies (GWAS) have linked various genetic polymorphisms (e.g., HLA*B51, ERAP1) to an increased risk of BD, with particular focus on cytokine-related gene variants. Infectious agents, such as Streptococcus species and herpes simplex virus, along with oral and intestinal dysbiosis and molecular mimicry, are key environmental triggers of innate immune inflammation, which is further amplified by adaptive immune responses. The innate immune system's primary cells, including neutrophils and NK cells, are upregulated, leading to an overproduction of proinflammatory cytokines. Additionally, an imbalance in T cell populations, characterized by a decrease in Tregs and expansion of Th1 and Th17 cells, contributes to disease pathogenesis. This review provides an overview of recent advances in understanding BD's etiopathogenesis.
{"title":"Etiopathogenesis of Behçet's disease: A systematic literature review","authors":"Nabil Belfeki , Nouha Ghriss , Alexandre Le Joncour , David Saadoun","doi":"10.1016/j.clim.2025.110549","DOIUrl":"10.1016/j.clim.2025.110549","url":null,"abstract":"<div><div>Behçet's disease (BD) is a chronic, multisystemic inflammatory vasculitis affecting veins and arteries. Its etiopathogenesis remains unclear but is thought to result from genetic predisposition combined with environmental triggers. Recent genome-wide association studies (GWAS) have linked various genetic polymorphisms (e.g., HLA*B51, ERAP1) to an increased risk of BD, with particular focus on cytokine-related gene variants. Infectious agents, such as <em>Streptococcus</em> species and herpes simplex virus, along with oral and intestinal dysbiosis and molecular mimicry, are key environmental triggers of innate immune inflammation, which is further amplified by adaptive immune responses. The innate immune system's primary cells, including neutrophils and NK cells, are upregulated, leading to an overproduction of proinflammatory cytokines. Additionally, an imbalance in T cell populations, characterized by a decrease in Tregs and expansion of Th1 and Th17 cells, contributes to disease pathogenesis. This review provides an overview of recent advances in understanding BD's etiopathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110549"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505038","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 : 2025-10-01Epub Date: 2025-06-18DOI: 10.1016/j.clim.2025.110545
Mattia Russel Pantalone , Xinling Xu , Nerea Martín Almazán , Christina Gerstner , Marie Fischer , Marika Kvarnström , Cecilia Söderberg-Nauclér , Marie Wahren-Herlenius , Afsar Rahbar
Sjögren's disease (SD) is a chronic autoimmune disease characterized by immune-mediated damage to salivary and lacrimal glands. This study aimed to explore the potential link between SD and human cytomegalovirus (HCMV), by analyzing presence of HCMV proteins in salivary gland tissue specimens and prevalence of HCMV-specific antibodies in serum samples from SD patients and controls. HCMV-immediate early (IE) and late proteins (LA and pp65) were highly abundant in tissue specimens from SD patients (88.9 %, 69.2 %, 45.8 %, respectively), and less abundant in patients with Sicca symptoms without SD (70.5 %, 20.0 %, 12.5 %, respectively). Samples in the SD group were also positive at higher scores for the HCMV proteins than Sicca symptom patients without SD. IgM prevalence was higher in SD patients than in healthy controls (32.1 % vs. 13.4 %, P = 0.04) and HCMV-IgG titers were higher (P < 0.0001). Understanding the potential role of HCMV in SD pathogenesis may contribute to advancements in disease prevention and treatment.
{"title":"High activity of human cytomegalovirus in patients with Sjögren's disease","authors":"Mattia Russel Pantalone , Xinling Xu , Nerea Martín Almazán , Christina Gerstner , Marie Fischer , Marika Kvarnström , Cecilia Söderberg-Nauclér , Marie Wahren-Herlenius , Afsar Rahbar","doi":"10.1016/j.clim.2025.110545","DOIUrl":"10.1016/j.clim.2025.110545","url":null,"abstract":"<div><div>Sjögren's disease (SD) is a chronic autoimmune disease characterized by immune-mediated damage to salivary and lacrimal glands. This study aimed to explore the potential link between SD and human cytomegalovirus (HCMV), by analyzing presence of HCMV proteins in salivary gland tissue specimens and prevalence of HCMV-specific antibodies in serum samples from SD patients and controls. HCMV-immediate early (IE) and late proteins (LA and pp65) were highly abundant in tissue specimens from SD patients (88.9 %, 69.2 %, 45.8 %, respectively), and less abundant in patients with Sicca symptoms without SD (70.5 %, 20.0 %, 12.5 %, respectively). Samples in the SD group were also positive at higher scores for the HCMV proteins than Sicca symptom patients without SD. IgM prevalence was higher in SD patients than in healthy controls (32.1 % vs. 13.4 %, <em>P</em> = 0.04) and HCMV-IgG titers were higher (<em>P</em> < 0.0001). Understanding the potential role of HCMV in SD pathogenesis may contribute to advancements in disease prevention and treatment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"279 ","pages":"Article 110545"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336379","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 : 2025-09-01Epub Date: 2025-06-09DOI: 10.1016/j.clim.2025.110535
Siyuan Lai , Ning Li , Songyue Chen , Yanxin Wang , Dengxiao Hong , Wenyan Xu , Zhongxin Chen , Baiqing Li , Changhao Xie
Programmed cell death protein 1 (PD-1) expression on T cells has been implicated in the pathogenesis of autoimmune diseases; however, the functional role of programmed death-ligand 1 (PD-L1) expression on B cells remains insufficiently characterized, particularly in the context of CD4+ T cell–mediated regulation in systemic lupus erythematosus (SLE). Flow cytometric analysis revealed that PD-L1+ B cells exhibited upregulated surface expression of the co-stimulatory molecules CD80 and CD86, alongside a concomitant downregulation in the expression of the antigen-presenting molecule human leukocyte antigen DR (HLA-DR). Furthermore, an elevated frequency of class-switched PD-L1+ B cells was observed in the peripheral blood of patients with SLE. Using co-culture systems and transwell assays, we demonstrated that CD4+ T cells modulate PD-L1 expression on B cells via direct cell–cell interactions. Mechanistically, this regulation was shown to be dependent on bidirectional CD40/CD40L signaling. These findings advance our understanding of PD-L1-mediated immunoregulation in SLE pathogenesis and identify PD-L1+ B cells as potential targets for therapeutic intervention.
{"title":"Activated CD4+ T cells upregulate PD-L1 expression on B cells through CD40/CD40L signaling and direct contact in systemic lupus erythematosus","authors":"Siyuan Lai , Ning Li , Songyue Chen , Yanxin Wang , Dengxiao Hong , Wenyan Xu , Zhongxin Chen , Baiqing Li , Changhao Xie","doi":"10.1016/j.clim.2025.110535","DOIUrl":"10.1016/j.clim.2025.110535","url":null,"abstract":"<div><div>Programmed cell death protein 1 (PD-1) expression on T cells has been implicated in the pathogenesis of autoimmune diseases; however, the functional role of programmed death-ligand 1 (PD-L1) expression on B cells remains insufficiently characterized, particularly in the context of CD4<sup>+</sup> T cell–mediated regulation in systemic lupus erythematosus (SLE). Flow cytometric analysis revealed that PD-L1<sup>+</sup> B cells exhibited upregulated surface expression of the co-stimulatory molecules CD80 and CD86, alongside a concomitant downregulation in the expression of the antigen-presenting molecule human leukocyte antigen DR (HLA-DR). Furthermore, an elevated frequency of class-switched PD-L1<sup>+</sup> B cells was observed in the peripheral blood of patients with SLE. Using co-culture systems and transwell assays, we demonstrated that CD4<sup>+</sup> T cells modulate PD-L1 expression on B cells via direct cell–cell interactions. Mechanistically, this regulation was shown to be dependent on bidirectional CD40/CD40L signaling. These findings advance our understanding of PD-L1-mediated immunoregulation in SLE pathogenesis and identify PD-L1<sup>+</sup> B cells as potential targets for therapeutic intervention.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"278 ","pages":"Article 110535"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263981","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 : 2025-09-01Epub Date: 2025-05-24DOI: 10.1016/j.clim.2025.110532
Gabriella Dobra , Edina Gyukity-Sebestyen , Matyas Bukva , Timea Boroczky , Szabolcs Nyiraty , Barbara Bordacs , Tamas Varkonyi , Andrea Kocsis , Zoltan Szabo , Gabor Kecskemeti , Tamas Ferenc Polgar , Marta Szell , Krisztina Buzas
Post-COVID syndrome affects 10–35 % of COVID-19 patients, and up to 85 % of hospitalized individuals, underscoring the need for early identification of high-risk cases. We hypothesized that the proteomic profile of serum small extracellular vesicles (sEVs) obtained during acute SARS-CoV-2 infection could predict post-COVID syndrome.
Serum samples from 59 patients, stratified as asymptomatic, moderate, or severe, were analyzed. sEVs were isolated, characterized by electron microscopy, nanoparticle tracking, and flow cytometry, then profiled via LC-MS.
Classification models integrating comorbidities, acute symptoms, and sEV proteomics distinguished the three groups, with sEV data outperforming conventional measures. Of 620 identified proteins, 30 showed significant differences between symptomatic and asymptomatic patients, including 12 linked to complement activation. ELISA confirmed LC-MS results that serum sEVs of post-COVID patients had altered C1 inhibitor, C3, and C5 levels.
These results suggest that sEV-based proteomics can enable earlier detection and more targeted follow-up for individuals at risk of post-COVID syndrome.
{"title":"Proteomic profiling of serum small extracellular vesicles predicts post-COVID syndrome development","authors":"Gabriella Dobra , Edina Gyukity-Sebestyen , Matyas Bukva , Timea Boroczky , Szabolcs Nyiraty , Barbara Bordacs , Tamas Varkonyi , Andrea Kocsis , Zoltan Szabo , Gabor Kecskemeti , Tamas Ferenc Polgar , Marta Szell , Krisztina Buzas","doi":"10.1016/j.clim.2025.110532","DOIUrl":"10.1016/j.clim.2025.110532","url":null,"abstract":"<div><div>Post-COVID syndrome affects 10–35 % of COVID-19 patients, and up to 85 % of hospitalized individuals, underscoring the need for early identification of high-risk cases. We hypothesized that the proteomic profile of serum small extracellular vesicles (sEVs) obtained during acute SARS-CoV-2 infection could predict post-COVID syndrome.</div><div>Serum samples from 59 patients, stratified as asymptomatic, moderate, or severe, were analyzed. sEVs were isolated, characterized by electron microscopy, nanoparticle tracking, and flow cytometry, then profiled via LC-MS.</div><div>Classification models integrating comorbidities, acute symptoms, and sEV proteomics distinguished the three groups, with sEV data outperforming conventional measures. Of 620 identified proteins, 30 showed significant differences between symptomatic and asymptomatic patients, including 12 linked to complement activation. ELISA confirmed LC-MS results that serum sEVs of post-COVID patients had altered C1 inhibitor, C3, and C5 levels.</div><div>These results suggest that sEV-based proteomics can enable earlier detection and more targeted follow-up for individuals at risk of post-COVID syndrome.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"278 ","pages":"Article 110532"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149630","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 : 2025-09-01Epub Date: 2025-05-27DOI: 10.1016/j.clim.2025.110533
Na Chen , Leidan Zhang , Xinyue Wang , Zhijiao He , Di Wang , Juan Du , Meiju Deng , Mengyuan Zhang , Meiqing Jiang , Yuqing Wei , Meng Zhao , Ying Liu , Xiaolei Wang , Hongxin Zhao , Yaxian Kong
Persistent immune activation is a key factor contributing to AIDS progression and non-AIDS-associated complications. NKT-like cells were found to exert immunosuppressive roles under some pathological situations by Foxp3 upregulation. Here, we found that Foxp3 was mainly expressed on CD4+NKT-like cells in untreated people living with HIV (PLWH) and the frequencies of Foxp3+CD4+NKT-like cells were correlated with HIV disease progression. Furthermore, the percentage of Foxp3+CD4+NKT-like cells was positively associated with immune activation and systematic inflammation. Foxp3+CD4+NKT-like cells might exert immunomodulatory effects by elevating the expression of TGF-β, IL-10, CD39, CD25, GITR, Ki67 and TIGIT. However, our analyses further identified Foxp3+CD4+NKT-like cells as a distinct subset that differed from conventional regulatory T cells. Notably, patients with higher baseline levels of Foxp3+CD4+NKT-like cells had a greater risk of poor immune reconstitution. These findings emphasized the importance of Foxp3+CD4+NKT-like cells during HIV infection and revealed its predictive role in immune reconstitution.
{"title":"Increased levels of Foxp3+CD4+NKT-like cells are associated with HIV disease progression","authors":"Na Chen , Leidan Zhang , Xinyue Wang , Zhijiao He , Di Wang , Juan Du , Meiju Deng , Mengyuan Zhang , Meiqing Jiang , Yuqing Wei , Meng Zhao , Ying Liu , Xiaolei Wang , Hongxin Zhao , Yaxian Kong","doi":"10.1016/j.clim.2025.110533","DOIUrl":"10.1016/j.clim.2025.110533","url":null,"abstract":"<div><div>Persistent immune activation is a key factor contributing to AIDS progression and non-AIDS-associated complications. NKT-like cells were found to exert immunosuppressive roles under some pathological situations by Foxp3 upregulation. Here, we found that Foxp3 was mainly expressed on CD4<sup>+</sup>NKT-like cells in untreated people living with HIV (PLWH) and the frequencies of Foxp3<sup>+</sup>CD4<sup>+</sup>NKT-like cells were correlated with HIV disease progression. Furthermore, the percentage of Foxp3<sup>+</sup>CD4<sup>+</sup>NKT-like cells was positively associated with immune activation and systematic inflammation. Foxp3<sup>+</sup>CD4<sup>+</sup>NKT-like cells might exert immunomodulatory effects by elevating the expression of TGF-β, IL-10, CD39, CD25, GITR, Ki67 and TIGIT. However, our analyses further identified Foxp3<sup>+</sup>CD4<sup>+</sup>NKT-like cells as a distinct subset that differed from conventional regulatory T cells. Notably, patients with higher baseline levels of Foxp3<sup>+</sup>CD4<sup>+</sup>NKT-like cells had a greater risk of poor immune reconstitution. These findings emphasized the importance of Foxp3<sup>+</sup>CD4<sup>+</sup>NKT-like cells during HIV infection and revealed its predictive role in immune reconstitution.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"278 ","pages":"Article 110533"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181590","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 : 2025-09-01Epub Date: 2025-06-06DOI: 10.1016/j.clim.2025.110537
Xinyue Zhang , Peixuan Liang , Ziwei Hu , Ziyun Zhang , Shaozhe Cai , Lingli Dong
This nested case-control study explored the clinical features and risk factors of Parvovirus B19 (B19V) infection in autoimmune rheumatic inflammatory disease (AIIRD) patients. A total of 86 B19V-positive cases and 172 matched controls were analyzed. Chronic liver diseases, cardiovascular diseases, a higher number of total infections, and the use of Mycophenolate Mofetil (MMF) were associated with an increased risk of B19V infection, whereas Iguratimod (IGU) was identified as a protective factor. Anemia, pneumonia, fever, myalgia, and hepatitis were significantly more common in B19V-infected patients, who were also more likely to experience varying degrees of cytopenia, particularly pancytopenia. Secondary hemophagocytic syndrome potentially attributable to B19V infection was observed in the case. Laboratory results showed lower blood cell counts and electrolytes, and higher anti-histone antibody positivity. Serum calcium, complement C4, and IgM were identified as key predictors in logistic and Lasso regression models.
Trial registration
Chinese Clinical Trial Register; https://www.chictr.org.cn/; ChiCTR2400089902.
{"title":"Clinical characteristics, risk factors and predictors of Parvovirus B19 infection in patients with autoimmune rheumatic inflammatory diseases: A nested case–control study","authors":"Xinyue Zhang , Peixuan Liang , Ziwei Hu , Ziyun Zhang , Shaozhe Cai , Lingli Dong","doi":"10.1016/j.clim.2025.110537","DOIUrl":"10.1016/j.clim.2025.110537","url":null,"abstract":"<div><div>This nested case-control study explored the clinical features and risk factors of Parvovirus B19 (B19V) infection in autoimmune rheumatic inflammatory disease (AIIRD) patients. A total of 86 B19V-positive cases and 172 matched controls were analyzed. Chronic liver diseases, cardiovascular diseases, a higher number of total infections, and the use of Mycophenolate Mofetil (MMF) were associated with an increased risk of B19V infection, whereas Iguratimod (IGU) was identified as a protective factor. Anemia, pneumonia, fever, myalgia, and hepatitis were significantly more common in B19V-infected patients, who were also more likely to experience varying degrees of cytopenia, particularly pancytopenia. Secondary hemophagocytic syndrome potentially attributable to B19V infection was observed in the case. Laboratory results showed lower blood cell counts and electrolytes, and higher anti-histone antibody positivity. Serum calcium, complement C4, and IgM were identified as key predictors in logistic and Lasso regression models.</div></div><div><h3>Trial registration</h3><div>Chinese Clinical Trial Register; <span><span>https://www.chictr.org.cn/</span><svg><path></path></svg></span>; ChiCTR2400089902.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"278 ","pages":"Article 110537"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240510","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号