Clinical and experimental immunology最新文献

{"title":"SOCS1 Haploinsufficiency in a Patient with Granulomatous Interstitial Lung Disease and Inflammatory Bowel Disease-like Disease.","authors":"Gamze Sonmez, Ismail Yaz, Ceren Ustun, Ali Şahin, Gulnar Aliyeva, Elif Babaoglu, Guzin Özden, Sevil Oskay Halacli, Deniz Cagdas","doi":"10.1093/cei/uxag023","DOIUrl":"https://doi.org/10.1093/cei/uxag023","url":null,"abstract":"<p><strong>Introduction: </strong>SOCS1 haploinsufficiency is an inborn error of immunity with dysregulated JAK-STAT signaling and heterogeneous autoimmune, infectious, and inflammatory phenotypes; its spectrum and management remain unclear.</p><p><strong>Methods: </strong>We report a 29-year-old woman with a novel heterozygous SOCS1 variant (c.494C>T; p.Pro165Arg) identified by whole-exome sequencing. Variant impact was assessed in silico (CADD, conservation mapping, AlphaFold3, PremPS) and functionally by measuring total and phosphorylated STAT1 expression in patient vs control cells at baseline and after IFN-γ stimulation. We also reviewed data from 20 previously reported SOCS1-deficient patients.</p><p><strong>Results: </strong>The patient had granulomatous lymphocytic interstitial lung disease (GLILD), rheumatoid arthritis, IBD-like enteropathy, and hypogammaglobulinemia, initially diagnosed with CVID. GLILD responded to rituximab; sirolimus was ineffective for enteropathy. Segregation revealed an asymptomatic father carrying the same variant. The patient was found to have an additional heterozygous TACI gene variant. Post-stimulation flow cytometry showed higher STAT1 (24.7 vs 5.8 MFI) and p-STAT1 (43.4 vs 2.4 MFI) levels; however, these differences were not statistically significant (p>0.05). Structural modeling predicted SH2-domain destabilization (ΔΔG +1.16 kcal/mol). Literature synthesis for SOCS1 deficiency patients (n=21) showed median symptom onset of 8 years (range 5 months-44 years), autoimmune diseases (immune thrombocytopenia, psoriasis, etc.), and frequent immunophenotypic abnormalities: lymphopenia 4/8 (50%); high IgE 5/7 (71.4%); low CD3+ 11/17 (64.7%); CD4+ 6/19 (31.5%); CD8+ 5/17 (29.4%); B cells 5/17 (29.4%); and NK cells 4/19 (21%).</p><p><strong>Conclusion: </strong>SOCS1 haploinsufficiency presents heterogeneous phenotypes with variable penetrance. Early genetic testing and targeted interventions, such as JAK inhibitors or cytokine-blocking biologics, may improve outcomes.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity between insulin and proinsulin in the potency for insulin autoantibodies (IAA) in newly diagnosed type 1 diabetes children.","authors":"Pantea Parsian, Rasmus Bennett, Cheng-Ting Tsai, Anita Ramelius, Åke Lernmark, Josefine Jönsson","doi":"10.1093/cei/uxag026","DOIUrl":"https://doi.org/10.1093/cei/uxag026","url":null,"abstract":"<p><strong>Introduction: </strong>Autoantibodies against insulin (IAA) are early appearing markers of autoimmunity against the pancreatic islet beta cells and predict progression to type 1 diabetes if additional islet autoantibodies also develop. It is still controversial if proinsulin rather than insulin is the primary autoantibody.</p><p><strong>Methods: </strong>The aim of the present study was to compare the half-maximal concentration (IC50) between insulin and proinsulin to displace the binding of insulin to insulin autoantibodies (IAA) in the Antibody Detection by Agglutination PCR (ADAP) assay.</p><p><strong>Results: </strong>IC50 as a measure of potency to displace insulin binding to IAA was determined in 36 newly diagnosed type 1 diabetes children. The ability of either insulin or proinsulin to displace IAA was heterogenous. Proinsulin curves were consistently right-shifted relative to insulin as median IC50 was 21.0 nM (IQR 14.9-25.1) for insulin and 26.1 nM (IQR 12.3-37.5) for proinsulin. A significant age × sex interaction was observed (F (1,31) = 14.3, p < 0.001), indicating that IC50 for both insulin and proinsulin increased with age in boys but decreased in girls. It may reflect whether autoantibodies to insulin or proinsulin was first appearing or of variable maturation from the time of initiation through progression to clinical onset.</p><p><strong>Conclusion: </strong>It was concluded that the IC50 of insulin and proinsulin for IAA was comparable in children with newly diagnosed type 1 diabetes. The ADAP IAA assay should prove useful to determine whether insulin or proinsulin is the primary target at the time of seroconversion to IAA.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent central nervous system infection with Candida and Mycobacterium intracellulare in CARD9 deficiency: immunological insights from a single case.","authors":"Tomonari Shigemura, Haruo Nagumo, Norimoto Koabayashi, Kazunaga Agematsu, Takamasa Saito, Takashi Kurata, Shiho Asaka, Tomomi Yamaguchi, Tomoki Kosho, Yozo Nakazawa","doi":"10.1093/cei/uxag024","DOIUrl":"https://doi.org/10.1093/cei/uxag024","url":null,"abstract":"<p><strong>Introduction: </strong>Caspase recruitment domain-containing protein 9 (CARD9) deficiency is classically characterized by chronic mucocutaneous candidiasis (CMC) and invasive Candida infections, including central nervous system (CNS) disease. Susceptibility to mycobacterial infection has not been considered a defining feature of CARD9 deficiency.</p><p><strong>Methods: </strong>We describe a patient with a typical clinical phenotype of CARD9 deficiency associated with compound heterozygous variants in CARD9, initially presenting with CMC and later manifesting CNS candidiasis, complicated by a concurrent CNS infection caused by Mycobacterium intracellulare. This unexpected finding prompted detailed immunological analyses to determine whether the mycobacterial infection represented a coincidental event or reflected an underlying susceptibility.</p><p><strong>Results: </strong>Immunological studies demonstrated preserved neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species production, whereas bactericidal/permeability-increasing protein (BPI) was uniquely and markedly reduced among neutrophil antimicrobial proteins. In parallel, monocyte-derived dendritic cells exhibited impaired tumor necrosis factor-α (TNF-α) production in response to mycobacterial stimulation, suggesting impaired cytokine responses downstream of CARD9.</p><p><strong>Conclusion: </strong>These findings suggest that impaired dendritic cell cytokine responses to mycobacteria, together with markedly reduced neutrophil BPI content, may have contributed to the development of M. intracellulare infection in this patient. Our study highlights a potential mechanism underlying susceptibility to mycobacterial infection in CARD9 deficiency.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BAFF-R Expression as a Potential Biomarker Associated with COVID-19 Vaccine Non-Responsiveness in Antibody-Deficient Patients.","authors":"Eleanor O'Callaghan, Adrian M Shields, Leon Chang, Michelle Umpierrez, Darren Newton, Siobhan O Burns, Alex G Richter, Gina Doody, Sinisa Savic","doi":"10.1093/cei/uxag004","DOIUrl":"https://doi.org/10.1093/cei/uxag004","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with primary and secondary antibody deficiencies exhibit variable responses to vaccination, with many failing to mount optimal immunity to SARS-CoV-2. Mechanisms underpinning vaccine non-responsiveness remain poorly defined and unpredictable. We hypothesised that B-cell-intrinsic features are associated with SARS-CoV-2 vaccine failure.</p><p><strong>Methods: </strong>Peripheral B-cells from 49 patients enrolled in the COVID-19 in Antibody Deficiency (COV-AD) study underwent a validated in vitro B-cell differentiation assay. We assessed plasmablast and plasma cell (PC) generation, immunoglobulin production, immunoglobulin heavy chain (IGH) repertoire diversity, and BAFF-R expression.</p><p><strong>Results: </strong>Vaccine non-responders displayed reduced IgA class-switched immunoglobulin production in vitro compared to healthy controls and responders. Moreover, while the relative percentage of PC output was comparable between groups, the overall number of cells obtained from non-responders was reduced. Most non-responders and a subset of responders exhibited reduced BAFF-R surface expression at baseline compared to healthy controls, though with considerable overlap between groups. BAFF-R transcript levels partially corresponded with surface expression but varied and did not clearly distinguish response. No compensatory upregulation of alternative BAFF receptors or elevated serum BAFF was observed. IGH repertoire analysis revealed preserved diversity among patients.</p><p><strong>Conclusions: </strong>Diminished BAFF-R expression is associated with vaccine non-responsiveness and may indicate underlying B-cell-intrinsic defects. BAFF-R shows potential as a candidate biomarker that merits further validation in larger, multicentre cohorts to determine its clinical utility for stratifying patients at risk of vaccine failure. These findings suggest that the BAFF/BAFF-R axis may play an important role in vaccine-induced humoral immunity in antibody-deficient patients, warranting further mechanistic investigation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving understandings for the roles of CD38 protein in autoimmunity and autoimmune disease.","authors":"Xiaochun Ye, Jieying Zhang, Mengping Song, Ping Wang, Irma Ares, Bernardo Lopez-Torres, Marta Martínez, María-Rosa Martínez-Larrañaga, Jorge-Enrique Maximiliano, Arturo Anadón, Xu Wang, María-Aránzazu Martínez","doi":"10.1093/cei/uxag014","DOIUrl":"10.1093/cei/uxag014","url":null,"abstract":"<p><p>Autoimmune diseases are chronic idiopathic disorders characterized by inflammatory responses. Cluster of differentiation 38 (CD38), a surface molecule with enzymatic and signalling capabilities, contributes to the regulation of NAD+ metabolism and mediates various intracellular pathways. Recent research has revealed the influence of the CD38 protein in the pathogenesis of autoimmune diseases. During inflammation, CD38 is involved in regulating biological processes such as cell recruitment, cell activation, cytokine and chemokine release, antigen presentation, and phagocytosis. Dysfunctional CD38 induces autoimmune diseases. CD38 is expressed at low levels in various haematopoietic systems and tissues but exhibits elevated expression in multiple myeloma and plasma cells. CD38-targeted monoclonal antibodies with favourable therapeutic effects have been discovered, such as isatuximab, daratumumab, and mezagitamab. Although CD38-targeted antibodies were originally developed to eliminate malignant immune cells and inhibit their strong activation, these monoclonal antibodies can also inhibit autoantibodies production in autoimmune diseases. CD38 protein is a promising biomarker of autoimmune disease diagnosis and a potential therapeutic target for the treatment of autoimmune diseases. In this review article, we will focus on the latest findings on the involvement of CD38 in autoimmunity and autoimmune disease and assess the value of research and therapeutic application of CD38 in disease control.</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/PMC13020543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431144","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":"PSMB8 stratifies therapy response in eosinophilic esophagitis.","authors":"Xinyi Wei, Sabrina Degen, Theresa Hironimus, Tobias Rechenauer, Katharina Yankouskaya, Aline Rückel, Margit Schmid, Daniel Rieger, Christoph Ehrsam, Adrian P Regensburger, Alexander Schnell, Anja Rabe, Anjona Schmidt-Choudhury, Andrea Tannapfel, Jan De Laffolie, Stefan Schumann, Tobias Schwerd, Hannes Hoelz, Ida Allabauer, Pooja Gupta, Wolfgang Krebs, Arndt Hartmann, Joachim Woelfle, Ralf Rieker, Andre Hoerning","doi":"10.1093/cei/uxag012","DOIUrl":"10.1093/cei/uxag012","url":null,"abstract":"<p><p>Proton pump inhibitors (PPIs) are an effective first-line treatment for eosinophilic esophagitis (EoE). However, half of the patients are refractory to PPI therapy, and predictive markers for therapy decision are lacking. Thus, this study aimed to investigate the differences in esophageal immunologic transcriptome between PPI-non-responders and PPI-responders and identify molecular biomarkers to guide therapy decisions. Forty-eight pediatric EoE patients were enrolled and classified due to PPI-therapy response. Pre-treatment esophagus biopsy was collected for gene expression analysis, differentially expressed genes (DEGs) between PPI-responders and non-responders were identified, followed by gene enrichment and protein-protein interaction network analyses. Expression of identified hub genes was confirmed by immunohistochemistry in an extended cohort comprising 62 patients. PPI-non-responders and responders exhibit a partially different transcriptomic profile, as 12 DEGs were up-regulated and one down-regulated. These DEGs are closely related to antigen processing and presentation function. PSMB8 was identified as a hub gene differing between these two groups, and immunohistochemistry confirmed significantly increased expression in PPI-non-responders (P < 0.0001). Notably, receiver operating characteristic curves curve analysis of PSMB8 reveals it as highly predictive for PPI response (sensitivity/specificity: 0.61/1.00). PPI-non-responding EoE patients exhibited a more profound dysregulation of gene expression. PSMB8 represents a promising esophageal biomarker for predicting therapy response in pediatric EoE.</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/PMC13062531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638177","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":"The 'target tissues' as orchestrators of autoimmune responses: the paradigm of Sjögren's syndrome.","authors":"Maria Filika, Stergios Katsiougiannis","doi":"10.1093/cei/uxaf078","DOIUrl":"10.1093/cei/uxaf078","url":null,"abstract":"<p><p>Systemic autoimmune diseases have been traditionally studied with a special focus on the immune system and less attention was paid to the roles of target tissues that are being exposed to the immune assault. For many common autoimmune diseases accumulating data unravel and highlight the potential role of the target tissues as orchestrators of the autoimmune responses. In this selective review, using Sjögren's disease (SjD) as a paradigm, we discuss the role of salivary gland epithelial cells (SGEC) not as innocent bystander targets of autoimmune responses, but rather as initiators and amplifiers of the inflammatory reactions. In fact, SGEC patients with Sjögren's disease are characterized by a unique phenotype which is capable of initiating and perpetuating both innate and adaptive immune responses in the glandular microenvironment. Aberrant expression and function of TLRs and IFN pathways, lymphocyte activating proteins as well as rewired cellular metabolism and antigen-presenting features, shape this distinct auto-antigenic phenotype of SGEC. These discoveries and ideas regarding the regulatory potential of the target SGEC in Sjögren's disease add a new dimension to our concept of regulatory circuits in autoimmunity.</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/PMC12782113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767213","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":3.8,"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":"IL-33 blockade attenuates vascular inflammation in a mouse model of Kawasaki disease vasculitis.","authors":"Thacyana T Carvalho, Benjamin L Ross, Prasant K Jena, Asli E Atici, Angela C Gomez, Michael C Fishbein, Emily A Aubuchon, Youngho Lee, Richard T Lee, Elizabeth A Jacobsen, Waldiceu A Verri, Shuang Chen, Timothy R Crother, Moshe Arditi, Magali Noval Rivas","doi":"10.1093/cei/uxaf086","DOIUrl":"10.1093/cei/uxaf086","url":null,"abstract":"<p><p>The immune mechanisms underlying Kawasaki disease (KD), a febrile systemic vasculitis in children, are poorly understood. Reports indicate elevated levels of circulating IL-33 in acute KD patients; however, if IL-33 contributes to the pathogenesis of KD vasculitis remains unclear. Here, we used the Lactobacillus casei cell wall extract (LCWE)-induced murine model of KD to determine the contribution of IL-33 to vasculitis development. We observed increased expression of Il33 transcripts and IL-33 protein in LCWE-induced cardiovascular lesions. Bone marrow chimera experiments suggest that IL-33 production by both hematopoietic and stromal cells is important for LCWE-induced KD vasculitis; however, single-cell RNA sequencing, spatial transcriptomics, and flow cytometric analysis revealed that stromal cells were the predominant sources of IL-33. Furthermore, immune cells infiltrating LCWE-induced cardiovascular lesions expressed Il1rl1 transcripts, coding for the IL-33 receptor ST2. In vitro stimulation of bone marrow-derived macrophages with IL-33 enhanced their production of IL-1b and TNF-α. In vivo blockade of IL-33, using either neutralizing IL-33 antibody or Il33-/- mice, effectively attenuated LCWE-induced cardiovascular inflammation. Our results indicate that IL-33 contributes to LCWE-induced vascular inflammation through redundant mechanisms across multiple immune cell subsets rather than a single population and highlight IL-33 as a potential therapeutic target.</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/PMC12803022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984570","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":3.8,"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}