Scandinavian Journal of Immunology最新文献

{"title":"Mild Phenotype in Functionally Validated STAT1 Gain-of-Function Disease Due to a Novel DNA-Binding Variant.","authors":"Bahri Can Duran, Caner Aytekin, Miyuki Tsumura, Erhan Bahadır, Serap Özmen, Satoshi Okada, Vivien Béziat, Anne Puel, Jean-Laurent Casanova","doi":"10.1111/sji.70154","DOIUrl":"10.1111/sji.70154","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis, infections, autoimmunity, and immune dysregulation; however, mutation-level determinants of phenotypic variability remain incompletely defined. We aimed to describe the clinical, immunologic, and functional features of four patients with STAT1-GOF disease, including three related patients carrying a novel DNA-binding domain (DBD) variant associated with a mild phenotype. Clinical manifestations, immunologic findings, and immune deficiency and dysregulation activity scores were analysed. Whole-exome sequencing (WES) with Sanger confirmation was performed, and the functional activity of the novel p.Leu400Pro variant was assessed using a gamma-activated sequence luciferase reporter assay after interferon-γ stimulation. All patients presented with early-onset chronic mucocutaneous candidiasis. Three related patients carrying p.Leu400Pro showed a mild, stable clinical course without severe infections or multisystem autoimmunity during a median follow-up of 8 years and had low disease activity scores. Functional analysis demonstrated increased IFN-γ-induced transcriptional activity compared with wild-type STAT1, reaching levels comparable to the established R274Q GOF control under the experimental conditions used and supporting a GOF effect. In contrast, an unrelated patient with p.Glu353Lys developed severe multisystem autoimmunity, lymphoproliferation, and bronchiectasis with high disease activity scores. Ruxolitinib led to clinical improvement and was used as bridging therapy before haematopoietic stem cell transplantation (HSCT). These findings identify a novel, functionally validated DNA-binding domain STAT1-GOF variant associated with a mild phenotype, supporting mutation-level risk stratification and individualized management. Targeted Janus kinase inhibition may help stabilize severe disease before transplantation.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 4","pages":"e70154"},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'T Cell Receptor Therapy Against Melanoma-Immunotherapy for the Future?'","authors":"","doi":"10.1111/sji.70157","DOIUrl":"https://doi.org/10.1111/sji.70157","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 4","pages":"e70157"},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombomodulin Shapes Thrombo-Inflammatory Interactions in Lupus Nephritis.","authors":"Mads Lamm Larsen, Lea Dich Pedersen, Annette Gudmann Hansen, Trine Korsgaard Hejlesen, Anders Bengtsson, Anne Voss, Ellen M Hauge, Susan Due Kay, Bent Deleuran, Julie B Larsen, Steffen Thiel, Anne Troldborg","doi":"10.1111/sji.70158","DOIUrl":"10.1111/sji.70158","url":null,"abstract":"<p><p>Lupus nephritis (LN) confers a disproportionate thrombotic risk in systemic lupus erythematosus (SLE) that is not fully explained by conventional cardiovascular risk factors. The underlying molecular mechanisms remain largely unknown. We aimed to characterize the thrombo-inflammatory profiles in LN compared with SLE without nephritis (SLE-NonLN), and contextualized these findings to primary antiphospholipid syndrome (APS), primary Sjögren's disease (SjD), and healthy controls. In a cross-sectional design, we included 325 patients with SLE from two Danish cohorts, 10 with primary APS, 45 with primary SjD, and 100 healthy controls. A predefined thrombo-inflammatory panel encompassing endothelial and platelet activation, coagulation, fibrinolysis, and complement pathways was assessed using immunoassays. Group differences were adjusted for clinical covariates and multiple testing. Multivariate patterns were examined using principal component analysis, correlation networks, and logistic regression. Thrombomodulin levels were higher in SLE-LN than in SLE-NonLN and remained associated with LN after multiple testing correction and adjustment for age, treatment exposure, and disease activity. Thrombomodulin showed a modest association with albuminuria but not with disease activity, anti-double-stranded DNA antibody levels, or secondary APS. Correlation networks demonstrated a dense, integrated thrombo-inflammatory structure in SLE-LN. In multivariable logistic regression, thrombomodulin and prednisolone use emerged as independent factors associated with LN. LN is characterized by a distinct thrombo-inflammatory profile dominated by endothelial activation, with thrombomodulin emerging as the most consistent biological marker of renal involvement in SLE. The coordinated alterations observed across multiple pathways highlight the potential value of systems-oriented approaches for advancing mechanistic understanding in LN.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 4","pages":"e70158"},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes From Toll-Like Receptor 4-Stimulated Lung Cancer Cells Modulate Macrophage Polarization.","authors":"Başak Dalkıran, Ranya Erdal, Hande Canpınar","doi":"10.1111/sji.70159","DOIUrl":"https://doi.org/10.1111/sji.70159","url":null,"abstract":"<p><p>Exosomes derived from lung cancer cells play a critical role in modulating the tumour microenvironment, particularly through their effects on macrophage polarization. We investigated how exosomes from A549 lung adenocarcinoma cells, both unstimulated and stimulated with a toll-like receptor 4 (TLR4) agonist, influence the phenotype and function of THP-1 derived macrophages. We used differential centrifugation and immunobead assay to isolate exosomes. Exosomes from unstimulated A549 cells promoted a mixed M1/M2 macrophage phenotype with a bias towards M2 polarization, while exosomes from TLR4-stimulated A549 cells reduced M2 marker expression without affecting M1 polarization. Both types of exosomes increased macrophage phagocytic capacity compared to PMA-differentiated controls, but TLR4-agonists did not increase it further. These findings provide new insights into how TLR agonist-stimulated lung cancer-derived exosomes shape macrophage phenotypes and functions, with implications for understanding tumour-immune interactions and developing novel therapeutic strategies targeting the tumour microenvironment.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 4","pages":"e70159"},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Recovery in Tuberculosis is Associated With the Functional Remodelling of Ag85A-Specific Antibody Avidity and Phagocytic Activity.","authors":"Juan Diego Jibaja, Cheaylhi Sanchez, Alessia Piamonte, Sandra Palma Albornoz, Iskra Tuero","doi":"10.1111/sji.70156","DOIUrl":"https://doi.org/10.1111/sji.70156","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a critical global health threat. While research has historically prioritized T-cell immunity, antibodies against highly immunogenic candidates like the Mtb antigen Ag85A are increasingly recognized for their protective roles via Fcγ receptor-mediated effector functions. This study characterized the longitudinal dynamics of B-cells and phagocyte populations alongside Mtb-specific antibody features during TB treatment. A cohort of 20 patients with active TB was followed prospectively for 6 months, with peripheral blood samples collected at baseline (T0), at two (T2) and 6 months (T6) of therapy. The frequencies of circulating immune cells were analysed by flow cytometry, while Ag85A-specific avidity and phagocytic activity were evaluated in patient plasma. Our findings demonstrate a significant, coordinated shift in the host immune profile during anti-TB therapy. We observed a progressive increase in Mtb-specific phagocytic activity and antibody avidity after treatment completion, indicating a functional remodelling of the immune response. Specifically, Ag85A-specific IgG1 levels correlated with phagocytic activity, suggesting it acts as a primary mediator of this effector response. Concurrently, maturation of antibody avidity correlated negatively with bacillary burden. As bacterial load, quantified by sputum smear test (SST), diminished, we noted a concomitant declining trend in circulating CD14⁺ monocyte and CD66⁺ granulocytes, indicating a gradual resolution of the inflammatory response. Strikingly, this contraction of the myeloid compartment inversely mirrored a progressive rise in circulating B cell frequencies. This integrated framework outperforms conventional metrics, providing a multi-parametric fingerprint that would be used to track treatment responses and design the next generation of TB immunotherapy.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 4","pages":"e70156"},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Infections and Refractory Lymphoproliferation Associated With a Novel PRKCD Variant: A Case Report of Successful Haematopoietic Stem Cell Transplantation.","authors":"Büşra Koçali, Saliha Esenboğa, Elif Soyak Aytekin, İsmail Yaz, Ayşe Demirçubuk, Ekrem Ünal, Deniz Çağdaş","doi":"10.1111/sji.70152","DOIUrl":"https://doi.org/10.1111/sji.70152","url":null,"abstract":"<p><p>Lymphoproliferation is a common manifestation of inborn errors of immunity and may delay diagnosis when it is the initial presentation. A nine-year-old girl developed recurrent lymphadenopathy from two years of age, accompanied by recurrent infections, anaemia and growth retardation. Whole-exome sequencing identified a homozygous PRKCD missense variant. Lymph node biopsy revealed florid follicular hyperplasia with cytomegalovirus (CMV) activation, and CMV viremia was detected. Despite immunoglobulin replacement, valganciclovir and immunomodulatory therapy, lymphoproliferation persisted. Haematopoietic stem cell transplantation was successfully performed, highlighting the importance of early genetic diagnosis and timely curative treatment in these patients.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 4","pages":"e70152"},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Analysis Between Increased CD63 Expression Detected by Eosinophil Activation Test and sIgE Levels.","authors":"Qianyun Li, Huagong Gao, Zhao Wang, Fengxia Guo","doi":"10.1111/sji.70150","DOIUrl":"10.1111/sji.70150","url":null,"abstract":"<p><p>This study evaluated the diagnostic utility of eosinophil activation testing in allergic rhinitis (AR) by monitoring CD63 and FcεRI expression on peripheral blood eosinophils before and after allergen stimulation. We enrolled 59 AR patients, 35 non-allergic rhinitis (NAR) patients, and 19 healthy controls (HC), stratified by sIgE results and clinical symptoms. Eosinophils were identified via flow cytometry as CCR3+ cells. We quantified baseline eosinophil counts and CD63/FcεRI expression, and then measured their changes following stimulation with 0.1 and 1.0 μg/mL dust mite allergen. Diagnostic accuracy was assessed using ROC analysis and Spearman's correlation with sIgE as the reference standard. AR patients had higher baseline eosinophil counts and CD63 expression than NAR or HC (p < 0.05). FcεRI was elevated in both AR and NAR relative to HC. Upon allergen stimulation, CD63 increased significantly only in AR, and this increase was dose-dependent (p < 0.05); FcεRI showed no response in any group. In this exploratory cohort, CD63 showed promising discriminatory ability, with an AUC of 0.899 (0.1 μg/mL) and 0.994 (1.0 μg/mL); a moderate positive correlation with sIgE was also observed (r = 0.358-0.461). In contrast, FcεRI performed around chance level (AUC 0.534-0.544). The eosinophil CD63 activation test can detect allergen-specific responses in AR and shows a moderate positive correlation with sIgE, suggesting potential as a complementary tool for AR diagnosis.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 3","pages":"e70150"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"51st Annual Meeting of the Scandinavian Society for Immunology (SSI), 7-10 September 2026, Bergen, Norway.","authors":"","doi":"10.1111/sji.70148","DOIUrl":"10.1111/sji.70148","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 Suppl 1 ","pages":"e70148"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Factor Kappa B (NF-κB)1 and NF-κB2 Deficiency: An Unpredictable Defect With Wide Clinical and Immunologic Phenotype.","authors":"Selin Sevinç, Candan İslamoğlu, Şule Haskoloğlu, Gökcan Öztürk, Sevgi Köstel Bal, Ayşen Durak Aslan, Seda Kaynak Şahap, Cevriye Cansız Ersöz, Tanıl Kendirli, Figen Doğu, Aydan İkincioğulları","doi":"10.1111/sji.70142","DOIUrl":"10.1111/sji.70142","url":null,"abstract":"<p><p>The Nuclear Factor Kappa B (NF-kB) signalling pathway is essential for regulating inflammation, cell survival, and adaptive immune responses through its canonical (NF-κB1-associated) and noncanonical (NF-κB2-associated) branches. The canonical pathway mediates rapid and broad reactions to immune stimuli, whereas the noncanonical pathway is activated by specific signals and contributes to lymphoid organ development, B-cell maturation including germinal centre activity, T-cell differentiation, thymic selection and antiviral defence. NF-κB transcription factors consist of five subunits: NF-kB1 (p105/p50), NF-kB2 (p100/p52), RelA, RelB and c-Rel-and heterozygous variants in NFKB1 or NFKB2 genes result in a wide range of immune dysregulation. NFKB1 mutations have been associated with common variable immunodeficiency, autoinflammatory or rheumatologic manifestations, Epstein-Barr virus-related lymphoproliferation, gastrointestinal involvement and susceptibility to recurrent or opportunistic infections. Clinical features of NFKB2 deficiency show considerable variability depending on mutation location, but recurrent infections and hypogammaglobulinemia remain the most frequently reported findings. Despite growing recognition of NF-κB-related inborn errors of immunity, the phenotypic spectrum continues to expand and genotype-phenotype correlations remain challenging. In this study, we describe seven individuals from five families with NFKB1 or NFKB2 variants and demonstrate considerable clinical and immunological heterogeneity, including marked intrafamilial variability.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 3","pages":"e70142"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SSI 2026: Time for the 51th Annual Meeting of the Scandinavian Society for Immunology in Beautiful Bergen.","authors":"Petter Höglund","doi":"10.1111/sji.70147","DOIUrl":"10.1111/sji.70147","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"104 Suppl 1 ","pages":"e70147"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}