Clinical and experimental immunology最新文献

{"title":"The many faces of cytokine storm syndrome: immunopathogenic mechanisms and clinical implications for a better patient management.","authors":"Piero Ruscitti","doi":"10.1093/cei/uxag039","DOIUrl":"10.1093/cei/uxag039","url":null,"abstract":"<p><p>Cytokine storm syndrome is a life-threatening hyperinflammatory condition characterized by excessive and dysregulated immune activation, leading to multiorgan dysfunction and poor clinical outcomes if not promptly recognized and adequately treated. Rather than representing a single disease entity, cytokine storm syndrome is increasingly understood as a final common pathogenic pathway shared by a broad spectrum of clinical conditions converging on overlapping immunopathological mechanisms driven by sustained cytokine production, immune-cell hyperactivation, and failure of immune-regulatory pathways. The clinical presentation of cytokine storm syndrome is characterized by a rapidly progressive nature, multisystem involvement, and the diagnostic challenges arising from nonspecific symptoms and overlapping laboratory features. Hyperferritinaemia emerges as a central laboratory hallmark with both diagnostic and potential pathogenic relevance. Therapeutic management of cytokine storm syndrome requires early recognition and is guided by three core principles: supportive care for organ dysfunction, control of underlying triggers, and timely immunomodulatory or immunosuppressive interventions. Overall, cytokine storm syndrome represents a complex and heterogeneous clinical syndrome in which improved mechanistic understanding, biomarker development, and tailored therapeutic strategies are essential to optimize patient outcomes.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367562","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":"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":3.9,"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":"Rare STAT1 variants in Moroccan tuberculosis patients: insights into host genetic susceptibility.","authors":"Sanae Zaidi, Aniss Rafik, Hanaa Skhoun, Zouhair Elkarhat, Aya Guennoun, Fatima Tabehout, Abderrahmane Errami, Ahmed Abid, Ismail Abderrhamani Ghorfi, Hanane El Ouazzani, Hicham Souhi, Adil Zegmout, Amal El Hassani, Fatima Ailal, Rachid Abilkassem, Zohra Ouzzif, Ibtihal Benhsaien, Ahmed Aziz Bousfiha, Jamila El Baghdadi","doi":"10.1093/cei/uxag006","DOIUrl":"10.1093/cei/uxag006","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a major public health concern, particularly in Morocco. The JAK/STAT signaling pathway, activated by interferon-gamma (IFN-γ), plays a crucial role in the immune response against intracellular mycobacteria. However, pathogenic variants in the STAT1 gene can lead to either impaired or dysregulated signaling, affecting host defense mechanisms. In this study, we investigated 245 patients for the contribution of rare heterozygous STAT1 variants in children and young adults with confirmed TB. Patients presented diverse clinical phenotypes, including both pulmonary and extrapulmonary forms of TB disease. Using an integrative approach combining next-generation sequencing, functional immunoassays targeting the IL-12/IL-23/IFN-γ axis, and in silico analyses, we identified eight rare missense variants among eight cases (one mutation per patient): p.Asp65Gly, p.Glu157Lys, p.Ala267Val, p.Gln340Arg, p.Phe364Leu, p.Leu498Val, p.Lys652Glu, and p.Met691Val. These variants were located in key functional domains of the STAT1 protein. Statistical analysis using Mann-Whitney U test demonstrated markedly reduced cytokine production in patient cells following BCG + IFN-γ stimulation (median: 1117 vs. 3328 in controls; P = 0.038), demonstrating a targeted deficiency in IFN-γ-mediated signaling. In silico predictions and 3D structural modeling indicated that these variants could destabilize the protein through altered hydrogen bonding and hydrophobic interactions. The previously reported variants, including the GOF variant p.Ala267Val and the LOF variants p.Glu157Lys, p.Leu498Val, and p.Met691Val, impair STAT1 activation or its nuclear translocation, thereby disrupting IFN-γ-mediated signaling and weakening host immune defense against Mycobacterium tuberculosis. Additionally, this study identified novel variants, comprising the GOF variant p.Asp65Gly and the LOF variants p.Gln340Arg, p.Phe364Leu, and p.Lys652Glu.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141110","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":"Development of a score derived from full blood count parameters to differentiate individuals with tuberculosis disease from those with tuberculosis infection.","authors":"Giusto Davide Badami, Bartolo Tamburini, Miriana Fallo, Mojtaba Shekarkar Azgomi, Francesco Dieli, Nadia Caccamo, Marco Pio La Manna","doi":"10.1093/cei/uxaf084","DOIUrl":"10.1093/cei/uxaf084","url":null,"abstract":"<p><p>In 2022, tuberculosis (TB) caused 1.3 million deaths worldwide, making it the second leading infectious cause of death. Diagnosing TB remains challenging because current immunological tests cannot distinguish between TB disease and TB infection (TBI). Research suggests that ratios such as monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte, along with absolute counts of various blood cells, could help develop a low-cost and easy-to-use diagnostic tool to distinguish TB disease from TBI among IFN-γ release assay (IGRA)-positive subjects without relying on microbiological tests. We enrolled 112 TB-infected subjects and used blood cell count parameters and ratios to develop a TB score that can indicate TB status. We then validated the score in another cohort of IGRA-positive hospitalized patients. We developed a TB score based on 11 blood parameters to identify TB disease among IGRA-positive subjects, with 93% specificity and 71% sensitivity. This score can support physicians in making therapeutic decisions for IGRA-positive subjects, offering a practical approach to differentiate TB disease from TBI.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809130","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":3.9,"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":"Case series on the efficacy of daratumumab in treating patients with anti-interferon-gamma autoantibodies.","authors":"Ky-Lyn Tan, Hari Chandana Ghanta, Lucinda Blake, Lourdes Ceron-Gutierrez, Tomas-Paul Cusack, Rainer Doffinger, Matthew Jenner, Shashank Sharma, Xi Ying Soo, Efrem Eren, Patrick F K Yong","doi":"10.1093/cei/uxag036","DOIUrl":"10.1093/cei/uxag036","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337988","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":3.9,"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":"Helios expression in naive CD4+ T cells decreases from neonates to older adults.","authors":"Hiroshi Mutoh, Takeo Mukai, Atsushi Ito, Tomoko Kawai, Hiromi Kamura, Kazuhiko Nakabayashi, Kohei Kashima, Mari Ichinose, Takayuki Iriyama, Shinya Takazawa, Mariko Yoshida, Yumi Tsuchida, Keishi Fujio, Naoto Takahashi","doi":"10.1093/cei/uxag041","DOIUrl":"10.1093/cei/uxag041","url":null,"abstract":"<p><p>Fetuses, neonates, and infants are vulnerable to infectious diseases. At the same time, they are exposed to many harmless antigens; therefore, suppressing unnecessary immune responses to maintain immune tolerance is a rational strategy. In the elderly, chronic inflammatory and autoimmune diseases are more likely to occur due to inappropriate and dysregulated immune responses. Helios, encoded by the IKZF2 gene, is a marker for natural regulatory T cells (Treg) but is also expressed at low levels in naive CD4+ T cells. Its expression decreases with age, which may contribute to an excessive immune response in older individuals. Flow cytometry and western blotting revealed that the decline in Helios expression begins in the early neonatal period and persists across subsequent life stages. Quantitative PCR showed that IKZF2 expression was significantly and strongly negatively correlated with age (decreased by 40% per decade). Integration of DNA methylation array data and public datasets identified significant age-associated epigenetic modifications within the IKZF2 gene body, which may partially explain the age-related reduction in its expression. Notably, these changes reflect a transition of naive CD4+ T cell characteristics: shifting from a \"Treg-like\" signature in neonates and infants-likely an adaptation to the extrauterine environment-toward a \"memory-like\" profile in older adults. In summary, Helios expression in human naive CD4+ T cells exhibits a continuous decline from the fetal stage through the neonatal, infant, childhood, adult, and elderly stages. This phenomenon may contribute to the shift from immune tolerance to immune response dominance over the course of aging.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403898","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":3.9,"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":"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":3.9,"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}