Scandinavian Journal of Immunology最新文献

{"title":"LTB4 Activates the MAP Kinase Pathway in Endothelial Cells to Cause Long-Lasting Neutrophil Tethering, MCP-1 and NO Releases.","authors":"Anne-Sofie Johansson, Jesper Z Haeggström, Jan Palmblad","doi":"10.1111/sji.70083","DOIUrl":"10.1111/sji.70083","url":null,"abstract":"<p><p>Leukotriene B₄ (LTB₄), a potent chemotactic and immune-modulating eicosanoid, signals via two receptors (BLT₁ and BLT₂), leading to rapid but transient migratory, adhesive and secretory responses in phagocytes. Previously, we reported that BLT₁ is the predominating BLT in human umbilical vein endothelial cells (HUVEC). However, little is known about how ligation of these receptors affects adhesive and secretory endothelial responses over time. Here, we demonstrate that in HUVEC, LTB₄ dose-dependently and stereospecifically causes a biphasic tethering of neutrophils, where the second phase is robust, similar to that induced by lipopolysaccharide, and persists for 3-8 h. LTB₄ also causes up-regulation of E-selectin, ICAM-1 and VCAM-1 and release of MCP-1 and nitric oxide (but not of IL-8 or HMGB1). These responses appeared to be mediated via BLT₁ and BLT₂ as judged by BLT₁ shRNA gene silencing and/or treatment with BLT₁ and BLT₂ specific antagonists prior to LTB₄ activation of HUVEC. Moreover, LTB₄ responses used primarily the MAP kinase/Erk pathway. Our findings suggest a new role for LTB₄ not only in early but also in late vascular inflammatory responses.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"103 1","pages":"e70083"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12759030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893335","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":"The New Insight Into the Role of Transcription Factors in the Function of Regulatory T Cells With Emphasis on FOXP3 and Its Implication in the Treatment of Autoimmune Disorders.","authors":"Afsaneh Shamsi, Mahdi Taghadosi, Fatemeh Khoobbakht","doi":"10.1111/sji.70086","DOIUrl":"https://doi.org/10.1111/sji.70086","url":null,"abstract":"<p><p>Peripheral immune tolerance is a cardinal feature of the adaptive immune system, which makes self-nonself discrimination and unresponsiveness toward self-antigens. Disruption in the regulation of these processes leads to damage to self-tissues and serious consequences, including autoimmune diseases. In the T cell compartment, the family of regulatory T cells (Treg cells) is the main component for the induction and maintenance of immune tolerance and preventing autoimmune diseases. Forkhead box P3 (FOXP3) is the key transcription factor for the function and Treg cell programming. Importantly, FOXP3 by itself is insufficient to completely specify the Treg cell program, suggesting that additional accessory transcription factors are involved both upstream and downstream, as well as alongside FOXP3, in directing Treg cell specification and its expression is controlled through various regulatory factors and epigenetic modifications. In the current review, we examine new insight into the regulatory mechanisms of Treg cell functions and programming with an emphasis on FOXP3, which opens new avenues for future therapeutic strategies of autoimmune disorders.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"103 1","pages":"e70086"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901054","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":"From Neoantigen Discovery to Immune-Checkpoint Synergy: Peptide Cancer Vaccines as Precision Tools for Personalised Cancer Therapy.","authors":"Abid H Banday, Meer Mehru Manzoor, Urooj Nissar, Seeham Jaleel","doi":"10.1111/sji.70084","DOIUrl":"10.1111/sji.70084","url":null,"abstract":"<p><p>The diagnosis, management and potential eradication of cancer depend on tumour type, stage, extent and anatomical location. While surgery, chemotherapy and radiotherapy remain central, advances in molecular oncology have shifted treatment toward personalised approaches. Identification of tumour-specific molecular abnormalities and biomarkers has enabled targeted therapies that eliminate malignant cells while limiting damage to normal tissues. Cancer immunotherapy has emerged as a promising, non-invasive strategy that activates the immune system to recognise and attack tumour-specific antigens. Preventive vaccines based on weakened or inactivated viruses have achieved notable success in reducing virus-associated cancers. Therapeutic vaccines targeting tumour-associated antigens (TAAs) and patient-specific neoantigens aim to elicit strong cytotoxic and helper T-cell responses against established tumours. Advances in genomic sequencing, bioinformatics-driven neoantigen prediction and single-cell profiling now enable accurate identification of tumour-specific targets. This review highlights progress in cancer vaccine research, focusing on strategies targeting TAAs, neoantigens and delivery platforms such as dendritic cell-based systems, nucleic acid vaccines (DNA and mRNA), synthetic long peptides and viral or bacterial vectors. Clinical evidence shows that neoantigen vaccines induce potent tumour-specific T-cell responses with minimal autoimmunity and gain enhanced efficacy when combined with immune checkpoint inhibitors or adoptive T-cell transfer (ACT) using tumour-infiltrating lymphocytes (TILs). By reinvigorating anti-tumour T cells within the tumour microenvironment, these combination approaches support durable tumour regression and improved outcomes. Despite unresolved challenges, advances in AI-guided target discovery, nanotechnology-based delivery systems and scalable manufacturing offer promising solutions for achieving precise and durable cancer treatment.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"103 1","pages":"e70084"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952991","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 'The Impact of Complement Factor H-Related Protein Gene Deletions on Kidney Transplantation'.","authors":"","doi":"10.1111/sji.70089","DOIUrl":"10.1111/sji.70089","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"103 1","pages":"e70089"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998935","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":"Methotrexate Exhibits a Dual Role in Regulation of CD4⁺ T Follicular Helper (Tfh) Cell Differentiation and Activity.","authors":"Sayan Chakraborty, Poulomi Khamaru, Altamas Hossain Daptary, Saikat Mukherjee, Soubhik Ghosh, Arindam Bhattacharyya","doi":"10.1111/sji.70071","DOIUrl":"10.1111/sji.70071","url":null,"abstract":"<p><p>Methotrexate (MTX) is one of the most prevalent drugs used in the treatment of autoimmune disorders as it has an established role in preventing T and B cell proliferation which reduces the severity of autoimmunity. However, MTX in combination with several other drugs is commonly used as chemotherapeutic regimens for the treatment of breast cancer (BC). Given the critical role of immune cells-particularly T and B cells-in recognising and eliminating tumor cells, we sought to investigate the impact of MTX on immune cell regulation in the context of breast cancer. CD4⁺ T follicular helper (Tfh) cells are recognised for their anti-tumor potential during BC progression, as they support B cell differentiation and proliferation within germinal centres. In this study, we specifically aimed to observe the regulatory role of MTX during in vitro human Tfh cell differentiation under normal circumstances, and within in vivo 4T1 metastatic tumour-bearing mice. Our findings reveal that MTX exerts a dual and context-dependent role in modulating Tfh cell differentiation and function across the two models. Furthermore, we explored the influence of the AMPK activator AICAR in combination with MTX in both the human and mouse models. MTX when used in combination with AICAR, rescued human Tfh cell differentiation in vitro from MTX-mediated suppression. In the 4T1 mouse model, the synergistic administration of MTX and AICAR significantly enhanced the proliferation of Tfh cells, along with increases in germinal centre B cells, memory B cells, and plasma cells in both circulation and tumor-draining lymph nodes.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"102 6","pages":"e70071"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661890","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":"The Impact of Complement Factor H-Related Protein Gene Deletions on Kidney Transplantation.","authors":"Salla Markkinen, A Inkeri Lokki, Ilkka Helanterä, Jarmo Ritari, Jukka Partanen, Seppo Meri, Kati Hyvärinen","doi":"10.1111/sji.70073","DOIUrl":"10.1111/sji.70073","url":null,"abstract":"<p><p>We recently reported that a homozygous deletion in the complement factor H-related (CFHR) locus predisposed kidney transplant patients to rejection. As donors carried intact genes, the susceptibility may have resulted from an alloimmune reaction to FHR proteins. However, we found no evidence for an anti-FH response. It is therefore possible that CFHR deletions as such affect the rejection risk. Here, we used MLPA and WGS to fine-map and sequence the CFHR region in rs7542235-GG patients, a SNP tagging for ΔCFHR3-1 deletion. Our results confirmed that all patients with this SNP harboured deletions of various sizes encompassing CFHR1. Furthermore, patients with homozygous ΔCFHR3-1 were homozygous for rs6677604-A, a SNP tagging for deletions of CFHR3-1 locus, confirming that allele A tags for deletion of both CFHR3 and CFHR1. Proteomics analyses in a larger population demonstrated that rs7542235-G and rs6677604-A associate with expression levels of several proteins involved in regulating alloimmune response. We observed that while increasing the rejection risk, the ΔCFHR3-1 did not associate with baseline disease or specific clinical characteristics. To conclude, the various deletion types found in patients shared the deletion of the CFHR1 gene confirming its association with variant rs7542235. Also, both deletion-tagging alleles are associated with altered expression of FHR proteins.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"102 6","pages":"e70073"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637605","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":"Diagnostic Performance of Three Serological Assays in Myasthenia Gravis: A Prospective Multicentre Study.","authors":"Laura Cuomo, Laura De Giglio, Maria Antonietta Isgrò, Maria Totaro, Matteo Pratali, Caterina Fragomeli, Lorenzo Cosmi, Francesco Annunziato, Boaz Palterer, Maria Concetta Altavista, Giovanni Antonini, Marianna Brienza, Chiara Cambieri, Francesca Cortese, Laura Fionda, Francesca Gragnani, Maurizio Inghilleri, Stefania Morino, Antonio Petrucci, Carlo Piantadosi, Eleni Anastasiadou, Marina Vitillo, Pankaj Trivedi, Elena Maria Pennisi","doi":"10.1111/sji.70072","DOIUrl":"10.1111/sji.70072","url":null,"abstract":"<p><p>Anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) autoantibody detection is crucial in the diagnosis and choice of treatment of myasthenia gravis (MG). We conducted a multicentre prospective study comparing radioimmunoprecipitation assay (RIPA), enzyme-linked immunosorbent assay (ELISA) and fixed cell-based assay (F-CBA) for anti-AChR and anti-MuSK antibody detection in 78 patients with suspected MG with at least 6 months of clinical follow-up. In the diagnosis of seropositive MG (anti-AChR+anti-MuSK abs), RIPA was most sensitive (82.8%) compared to ELISA (81.0%) and F-CBA (70.7%). F-CBA exhibited the highest specificity overall (95.0%). For anti-AChR detection, F-CBA demonstrated a sensitivity of 73.6% and specificity of 95.0%; ELISA showed sensitivity and specificity of 81.1% and 85.0%, respectively; and RIPA yielded sensitivity and specificity of 81.1% and 95.0%. Sensitivity of F-CBA improved when sera were tested at lower dilution (1:5) versus the manufacturer's recommended 1:10, without compromising specificity. Agreement among methods was almost perfect for anti-AChR detection (Cohen's Kappa > 0.81). For anti-MuSK detection, agreement was substantial between ELISA and RIPA, moderate between ELISA and F-CBA, and fair between RIPA and F-CBA. Higher anti-AChR antibody levels were found in generalised versus ocular MG by both RIPA and ELISA. F-CBA confirmed its optimal specificity while the sensitivity seems to be influenced by sample dilution. In conclusion, given the radioactive nature of RIPA and consequent limitations, F-CBA may represent a valid alternative in anti-AChR and anti-MuSK antibody detection in MG diagnosis. We suggest that the use of live-CBA or RIPA could be reserved for inconclusive cases.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"102 6","pages":"e70072"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597168","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":"Transforming Vitiligo Diagnosis and Treatment Through Artificial Intelligence: A Review.","authors":"Nasser Gholijani, Zahra Taheri, Maryam Bazgiri, Gholamhossien Darya, Zeinab Dehghan","doi":"10.1111/sji.70076","DOIUrl":"10.1111/sji.70076","url":null,"abstract":"<p><p>Vitiligo is a complex autoimmune disease of the skin characterised by the loss of melanocytes, resulting in depigmented patches on the skin. Despite advances in clinical diagnosis and treatment, challenges such as delayed diagnosis and limited therapeutic efficacy remain. Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has become a transformative tool in medical science, offering new approaches for early diagnosis, treatment optimization, and drug repurposing. This review examines the current status and recent advances in AI-based methods for vitiligo, highlighting deep neural network diagnostic tools, transformer-based image classifiers, and predictive models that surpass the accuracy of dermatologists. Moreover, AI-driven analyses of gene expression, protein interactions, and pharmacological networks have facilitated drug repurposing and accelerated therapeutic discovery. However, several challenges hinder the full clinical integration of AI. These include the need for large, diverse, high-quality datasets; limited representation of darker skin tones; lack of model interpretability; and ethical issues related to patient privacy, data ownership, and accountability for diagnostic errors. Integrating AI tools into existing healthcare systems also requires overcoming interoperability barriers and adapting clinical workflows. Addressing these challenges through the development of explainable, ethically governed, and inclusively trained AI systems will be crucial for realising the full potential of AI in improving vitiligo diagnosis and treatment outcomes.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"102 6","pages":"e70076"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701520","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":"Untargeted Metabolomic Profiling Reveals Lipid Metabolism Dysregulation in Patients With Immune Thrombocytopenia.","authors":"Xin Zhou, Yuqi Shi, Mengran Li, Jiarui Song, Ningning Shan","doi":"10.1111/sji.70077","DOIUrl":"10.1111/sji.70077","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterised by immune-mediated platelet destruction, yet its metabolic underpinnings remain incompletely understood. In this study, we applied a non-targeted serum metabolomics approach to characterise metabolic alterations in ITP and to explore candidate diagnostic biomarkers. A total of 37 serum samples were collected, including 20 from patients with ITP and 17 from age- and sex-matched healthy individuals. Global metabolite profiling was performed, followed by quantitative analyses, identification of differentially expressed metabolites, and functional annotation. Machine learning algorithms were then used to construct a diagnostic prediction model based on differential metabolites. Compared with healthy controls, ITP patients exhibited a distinct metabolic signature dominated by alterations in lipids and lipid-like molecules, with 680 metabolites upregulated and 589 downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed prominent involvement of lipid metabolism, cholesterol metabolism, and unsaturated fatty acid metabolism pathways. Among the differential metabolites, isopimpinellin and oleic acid emerged as highly characteristic of ITP. The prediction model built on these metabolomic features achieved a sensitivity of 78%, a specificity of 100%, and an area under the receiver operating characteristic curve of 0.83, indicating promising diagnostic performance. These findings suggest that dysregulated lipid metabolism is a central feature of ITP and support the potential of serum metabolomics-based machine learning models to aid in the identification of novel biomarkers and to improve early diagnosis of this immune-mediated thrombocytopenia.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"102 6","pages":"e70077"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744246","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":"Nonlinear Modelling Reveals a Refined Relationship Between Polymorphonuclear Leukocytes and Postsurgical Inflammatory and Organ Damage Responses.","authors":"Jordan A Phillips, Jonghoon Kang","doi":"10.1111/sji.70080","DOIUrl":"10.1111/sji.70080","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"102 6","pages":"e70080"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744169","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}