Clinical and experimental immunology最新文献

{"title":"Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a β2-adrenergic receptor-dependent manner.","authors":"Mehri Hajiaghayi, Fatemeh Gholizadeh, Niloufar Rahbari, Negaralsadat Emamnia, Steve C C Shih, Peter J Darlington","doi":"10.1093/cei/uxag018","DOIUrl":"10.1093/cei/uxag018","url":null,"abstract":"<p><strong>Introduction: </strong>Cancers often drive T cells toward an exhausted state characterized by impaired cytotoxicity and upregulation of inhibitory receptors (PD-1, TIM-3, CD38) and transcriptional regulators (TOX, NFATc1). Repeated stimulation in vitro is used to model this process, reflecting chronic antigen exposure in the tumor microenvironment. Stress-derived catecholamines further drive dysfunction through β-adrenergic receptor (β-AR) signaling. Here, we examined the impact of nebivolol, an atypical β1-AR blocker with β2-biased agonist activity, on T-cell exhaustion and cytotoxicity against breast cancer cells.</p><p><strong>Methods: </strong>Human CD3+ T cells from healthy participants were activated once (early activation) or four times (repeated activation) using CD3/CD28/CD2 T cell activator. Cells were treated in vitro with nebivolol, terbutaline (β2-agonist), isoproterenol (β1/β2-agonist), and metoprolol (β1-blocker). Exhaustion markers, including PD-1, TIM-3, CD38, and TOX, were measured by flow cytometry and RT-qPCR; NFATc1 by western blot; TNF and IFN-γ by ELISA, and cytotoxicity against MCF-7 breast carcinoma cells by co-culture assays. Disruption of the β2-AR gene (ADRB2) was achieved using CRISPR/Cas9.</p><p><strong>Results: </strong>Nebivolol reduced the proportion of TIM-3+CD38+PD-1+ T cells, downregulated TOX and nuclear NFATc1, and restored ADRB2 expression under repeated activation conditions. Nebivolol enhanced TNF secretion and improved cytotoxicity against MCF-7 cells. In contrast, terbutaline and isoproterenol had no significant effect on exhaustion markers or cytotoxicity. Metoprolol did not inhibit nebivolol's activity, indicating that its effects are not β1-AR-dependent. Disruption of ADRB2 indicated that nebivolol's anti-exhaustion effects are mediated by β2-AR.</p><p><strong>Discussion: </strong>These findings show that nebivolol reinvigorates CD4+ and CD8+ T cells following repeated activation, restoring their cytotoxic function against breast cancer cells in vitro. The immunomodulatory activity of Nebivolol is independent of β1-AR and mediated through β2-AR, suggesting that biased β2-AR signaling may represent a potential strategy for modulating T cell exhaustion in the tumor microenvironment.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies against type I interferons correlate with low CD169/SIGLEC1 and severe non-viral infections in ER patients.","authors":"Olga Staudacher, Tim Meyer, Bengisu Akbil, Miriam Mayer, Carolin Schmoll, Uwe Kölsch, Nadine Unterwalder, Anna Slagman, Christian Meisel, Christine Goffinet, Martin Möckel, Horst von Bernuth","doi":"10.1093/cei/uxaf074","DOIUrl":"10.1093/cei/uxaf074","url":null,"abstract":"<p><p>Neutralizing autoantibodies against type I interferons are a risk factor for multiple severe viral diseases. The timely detection of these autoantibodies remains an unmet need. We hypothesized that paradoxically low expression of type I IFN-induced CD169/SIGLEC1 expression analyzed by flow cytometry may allow rapid screening for the presence of these autoantibodies. In a prospective cohort study, we quantified monocytic CD169/SIGLEC1 expression and neutralizing autoantibodies against type I interferons in 808 patients who presented to the emergency room with signs of acute infections during the second wave of the SARS-CoV-2 pandemic in Germany in 2021. In patients, elevated CD169/SIGLEC1 (>2400 mAb/cell) demonstrated a negative predictive value of 100% for the detection of neutralizing autoantibodies against type I interferons. Low CD169/SIGLEC1 (<2400 mAb/cell) and a CRP >50 mg/L exhibited a positive predictive value of 70% for neutralizing autoantibodies against type I interferons. We further compared the adjusted odds ratio for mortality in patients with these autoantibodies to that in patients without autoantibodies against type I interferons. Neutralizing autoantibodies against type I interferons were associated with a worse clinical outcome, independent of SARS-CoV-2 infection, implying their presence is a risk factor for a worse general outcome.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Metrnl as a potential biomarker for renal involvement in ANCA-associated vasculitis.","authors":"Yuxin Jia, Dan Liu, Lin Yuan, Liping Xia, Hui Shen, Yuxuan Li, Jing Lu","doi":"10.1093/cei/uxaf087","DOIUrl":"10.1093/cei/uxaf087","url":null,"abstract":"<p><p>Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease characterized by significant renal involvement, yet identifying novel biomarkers for renal complications remains a clinical priority. Metrnl is a recently identified immunomodulatory cytokine implicated in inflammation, but its specific role in AAV has historically been unknown. To address this, this study investigated serum Metrnl levels via ELISA in 37 patients with microscopic polyangiitis (MPA), 17 with granulomatosis with polyangiitis (GPA), and 30 healthy controls (HCs), analysing correlations with clinical parameters such as the Birmingham Vasculitis Activity Score (BVAS) and renal function indicators under false discovery rate (FDR) correction. The results demonstrated that serum Metrnl levels were significantly elevated in both MPA and GPA patients compared to HCs and exhibited a strong positive correlation with BVAS in both subgroups. Crucially, following FDR adjustment, Metrnl levels showed significant correlations with key markers of renal impairment, including creatinine, cystatin C, and estimated glomerular filtration rate (eGFR). Stratification of MPA patients based on renal function (eGFR cut-off: 60 ml/min/1.73 m²) further revealed substantially higher Metrnl levels in those with impaired renal function. Receiver operating characteristic curve analysis indicated superior diagnostic efficacy for Metrnl in identifying AAV with renal involvement [area under the curve (AUC) = 0.8150] compared to diagnosing AAV overall (AUC = 0.7214). Collectively, these findings provide the first evidence that serum Metrnl is elevated in AAV and associated with disease activity and renal dysfunction, suggesting that Metrnl warrants further investigation as a potential biomarker for renal involvement in AAV.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.","authors":"Sangeeta Kumari, Katerina Pardali, Eric Meldrum, Christian Lood, Maarten Kraan","doi":"10.1093/cei/uxag011","DOIUrl":"10.1093/cei/uxag011","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and granule proteins released by activated neutrophils. While originally characterized as part of the innate immune response, NETs are now recognized as contributors to the pathogenesis of immune-mediated inflammatory diseases, including rheumatoid arthritis (RA). This review summarizes current clinical evidence linking NETs to RA, with a focus on their utility as biomarkers for disease activity and treatment response and their potential mechanistic role in disease progression. Elevated levels of NET components, such as myeloperoxidase-DNA complexes, citrullinated histones, and calprotectin, have been reported in RA and correlate with inflammatory markers and clinical disease activity scores. Treatment with biological disease-modifying anti-rheumatic drugs, including tumour necrosis factor alpha and interleukin-6 inhibitors, reduces NET markers, whereas persistent NET formation is associated with poor response. NETs also promote pathogenic processes, including anti-citrullinated protein antibody formation, Th17 activation, and osteoclastogenesis. Although no therapies currently target NET formation directly, preclinical studies using PAD4 inhibitors and antibodies against citrullinated histones show promising effects. Standardizing NET biomarkers and conducting longitudinal studies will be essential for clinical translation. Overall, NETs represent both a biomarker and a mechanistic driver in RA, offering a novel opportunity for therapeutic intervention.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An imbalance between CD80 and CD86 levels and CD4 regulatory T cell number and transendocytosis function exists in the liver in autoimmune hepatitis.","authors":"Neil Halliday, Alan Kennedy, Cayman Williams, Blagoje Soskic, Claudia Hinze, Massimo Pinzani, Douglas Thorburn, David M Sansom","doi":"10.1093/cei/uxag013","DOIUrl":"10.1093/cei/uxag013","url":null,"abstract":"<p><p>Impairment in Regulatory CD4 T cells (Treg) number and function have been implicated in autoimmune hepatitis (AIH). Treg are critical regulators of CD28 costimulation through CTLA4-mediated CD80 and CD86 control. We sought evidence for hepatic Treg frequency, phenotype, and function, and CD80/CD86 availability in AIH. Hepatic immune cells were isolated from eight patients with AIH and compared with cirrhotic and non-cirrhotic controls. Cells were assessed by flow cytometry and function was assessed by acquisition of CD80 from model antigen-presenting cells (APCs). We observed that Treg frequency was increased in AIH liver. Treg had an activated phenotype with a high CTLA4 expression and higher frequency of CTLA4 + PD1+ cells compared to non-AIH. Conventional CD4 T cells (Tcon) had an activated phenotype with increased HLA-DR expression, despite patients being in biochemical and histological remission. CD80 and CD86 expressions on B cells and monocytes were maintained or increased despite the excess of Treg, suggesting an imbalance between Treg and CD28 ligand availability. Hepatic Treg in AIH had preserved function for transendocytosis of CD80, which was enhanced by IL2 or IL10, demonstrating capacity for CD28 control. Overall, hepatic Treg have an activated phenotype and we did not observe reduced frequency or transendocytosis function of Treg in cirrhotic liver or (sub)acute liver failure from AIH. However, there is an imbalance between Treg function and CD80 and CD86 availability, with Tcon activation. This suggests that advanced AIH is not associated with reduced Treg frequency or function in the liver, but with an excess of CD80 and CD86.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating T-lymphocyte subsets as biomarkers for immune checkpoint inhibitors in solid tumors.","authors":"Yuehong Kong, Rongzheng Chen, Junjun Zhang, Liyuan Zhang","doi":"10.1093/cei/uxag002","DOIUrl":"10.1093/cei/uxag002","url":null,"abstract":"<p><p>Immune Checkpoint Inhibitors (ICIs) have become a mainstay in the treatment of various solid tumors. At present, commonly used predictive biomarkers include tumor mutation burden, programed death-ligand 1 expression levels, and microsatellite instability. However, these biomarkers face inherent limitations, such as the challenges associated with tumor tissue sampling and the inability to provide dynamic monitoring. In recent years, significant efforts have been undertaken for the precise characterization of circulating T-lymphocyte subsets, with their classification offering the potential to reflect the functional state of T cells and predict responses to ICI therapy. Its advantages in terms of sampling convenience and minimally invasive nature further highlight its feasibility as a dynamic monitoring tool. This review expounds on current research progress on the use of \"circulating\" T-lymphocyte subsets as predictors of ICI efficacy and discusses their reliability and potential as predictive tools.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12857432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological dysfunction associated with SARS-CoV-2 persistence in immunocompromised patients.","authors":"Ida M Johannsen, Line K Vibholm, Giacomo S Frattari, Miriam Rosas-Umbert, Irene H Tarpgaard, Merete Storgaard, Anna Karina Juhl, Maria L Pedersen, Emma F Iversen, Nanna B Andersen, Tine S Ebsen, Siri N H Svensgaard, Malthe Andreas, Peter Asdahl, Steffen Leth, Thomas A Rasmussen, Mariane H Schleimann, Martin Tolstrup","doi":"10.1093/cei/uxag022","DOIUrl":"10.1093/cei/uxag022","url":null,"abstract":"<p><p>Advances in coronavirus disease 2019 management has led to decreases in disease burden; however, immunocompromised patients continue to experience prolonged or persistent infections. We investigated immunological factors associated with time to viral clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised patients. By integrating clinical follow-up data, SARS-CoV-2-specific humoral and cellular response data, and single-cell RNA transcriptomic data, we uncovered differential immune responses between patients exhibiting short or long time-to-clearance (TTC), both at diagnosis and later during infection. We found that prolonged infection was associated with reduced SARS-CoV-2-specific humoral responses (P = 0.035) and diminished development of CD4+ and CD8+ T-cell activation (P = 0.045 and P = 0.038, respectively) despite levels of interferon-γ-producing T cells not being negatively affected. Baseline transcriptional profiles revealed increased immunological engagement of CD8+ cytotoxic T and natural killer (NK) cells among patients with prolonged TTC, potentially to compensate for impaired functional T-cell activation. Differential gene expression further pointed towards features of impaired T-cell functionality and exhaustion as contributors to prolonged TTC, including enrichment of NEAT1, CD52, and IL12RB2 in Long TTC patients. Our findings indicate that impaired viral clearance in some immunocompromised patients reflects an actively engaged yet dysregulated immune response. This underscores the complexity of immune dysfunction in this population and highlights the need for targeted interventions to restore effective, antiviral immunity, with a particular focus on regaining functional activation of antigen-specific T cells.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating concomitant RAG-2 and LRBA mutations in SCID and autoimmunity.","authors":"Ilia Spivak, Shirly Frizinsky, Amarilla Mandola, Atar Lev, Amos J Simon, Ortal Barel, Vicktoria Vishnevskia-Dai, Raz Somech, Ido Somekh","doi":"10.1093/cei/uxae083","DOIUrl":"10.1093/cei/uxae083","url":null,"abstract":"<p><p>Inborn errors of immunity (IEI) are a large heterogeneous group of diseases characterized by immunodeficiency, immune dysregulation, allergy, auto-inflammation, and predisposition to malignancies. Most are inherited as an autosomal recessive trait. We studied a patient with severe combined immunodeficiency (SCID) and immune dysregulation who harbored two distinct biallelic IEI-associated genetic mutations. Clinical, immunological, and genetic data were collected. Genetic investigation included whole-exome sequencing on DNA extracted from skin fibroblasts. Family segregation was performed by Sanger sequencing. Immunological evaluation included absolute and functional evaluations of lymphocytes and chimerism analysis post-hematopoietic stem cell transplantation (HSCT). Treg subsets, lipopolysaccharide-responsive and beige-like anchor (LRBA), and Cytotoxic T-Lymphocyte Associated protein 4 (CTLA4) expression levels were measured by flow cytometric analysis. A 19-year-old female patient from a consanguineous background underwent unconditioned matched sibling-related HSCT during infancy due to the clinical presentation of SCID with an Omenn phenotype. At that time, her underlying genetic defect was not defined. Years after HSCT, severe autoimmune phenomena were noted, including a systemic lupus erythematosus-like syndrome and ophthalmic manifestations. Genetic evaluation revealed biallelic homozygous mutations in recombination activating gene-2 (c.685C>T, p.Arg229Trp) and a previously undescribed mutation in LRBA (c.3325G>T, p.Asp1109Tyr). LRBA and CTLA4 expression levels were normal, suggesting that the LRBA variant identified in these kindred is unlikely to be pathogenic. Multiple genetic defects causing complex IEIs may be identified in the same individual in highly consanguineous populations. Functional immunological testing is essential for the evaluation of novel genetic variants.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen ameliorates psoriasis-like skin inflammation via inhibiting the cGAS-STING pathway.","authors":"Yubing Wu, Xiaoyu Wang, Yunqing Sun, Yuanyuan Duan, Min Zhang, Hong Sang, Pan Yu, Qingtao Kong","doi":"10.1093/cei/uxaf081","DOIUrl":"10.1093/cei/uxaf081","url":null,"abstract":"<p><p>Psoriasis is a chronic disease caused by abnormal immune system response, which is characterized by excessive keratinocyte proliferation and the activation of cytokine signaling pathways. In a previous study, we demonstrated in a psoriasis mouse model that hydrogen-rich water, an effective reactive oxygen species (ROS) scavenger, significantly improves disease severity. However, the precise molecular mechanism by which hydrogen helps in psoriasis treatment remains inadequately understood. This study assessed the role of hydrogen in suppressing keratinocyte hyperproliferation. We observed that the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene signaling was activated in psoriasis-like skin inflammation, which was dramatically inhibited by hydrogen treatment both in vitro and in vivo. Consistently, hydrogen decreased proliferative marker expression, including BCL2, BAX, and Ki-67, and significantly reduced ROS and inflammatory cytokines production. Our study suggests that molecular hydrogen could function as a potential treatment for psoriasis.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"220 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated type I interferon signature in patients with chronic granulomatous disease.","authors":"Ridhima Aggarwal, Pandiarajan Vignesh, Aditya Dod, Keshavamurthy Vinay, Saniya Sharma, Surjit Singh, Amit Rawat","doi":"10.1093/cei/uxag003","DOIUrl":"10.1093/cei/uxag003","url":null,"abstract":"<p><p>Chronic granulomatous disease (CGD) patients develop repeated infections and inflammatory complications. Underlying pathogenesis of hyperinflammation in CGD is not clearly characterized. To assess type-1 interferon signature and measure Siglec-1/CD169 expression on monocytes in patients with CGD. mRNA sequencing of PBMCs in five CGD patients and three controls was analysed for differentially expressed genes. Subsequently, 20 patients with CGD, 10 heterozygous carriers of CYBB mutations, 11 healthy controls and 11 patients of systemic lupus erythematosus (disease controls) were enrolled. Expression of CD169 on monocytes was measured using flowcytometry. Expression of five type 1 interferon signature genes (ISGs) was measured using RT-PCR. On transcriptome analysis of peripheral blood mononuclear cells, increased expression of type-1 ISGs were seen in CGD patients. Monocyte CD169 expression was compared across three subgroups of CGD patients (10 = inflammatory disease, 5 = infectious disease, 5 = asymptomatic disease). CD169 expression on monocytes (percentage and ΔMFI) was significantly high in inflammatory disease subgroup in comparison to asymptomatic disease subgroup of CGD (P = <0.001 and P = <0.001). Similarly, the expression was significantly high in inflammatory disease subgroup when compared to infection subgroup of CGD (P = 0.033 and P = 0.017). An elevated type-1 interferon score by RT-PCR was found in inflammatory disease subgroup in comparison to infection subgroup of CGD (P = 0.029) and healthy controls (P = 0.021). Percentage and ΔMFI of monocyte CD169 correlated with type 1 interferon scores, rp = 0.38 (P = 0.049) and rp = 0.46 (P = 0.017), respectively. CGD patients with hyperinflammatory manifestations exhibited a high type 1 interferon signature. CD169 is a reliable surrogate marker for estimation of type 1 interferon signature.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}