Frontiers in Immunology最新文献

{"title":"Enhancing pancreatic cancer treatment: the role of H101 oncolytic virus in irreversible electroporation.","authors":"Pu Xi, Dejun Zeng, Miao Chen, Lingmin Jiang, Yu Zhang, Dailei Qin, Zehui Yao, Chaobin He","doi":"10.3389/fimmu.2025.1546242","DOIUrl":"10.3389/fimmu.2025.1546242","url":null,"abstract":"<p><strong>Background: </strong>Irreversible Electroporation (IRE) offers a promising treatment for pancreatic cancer by using high-voltage pulses to kill tumor cells. But variations in tumor size and shape can lead to uneven electric fields, causing some cells to undergo only reversible electroporation (RE) and survive. However, RE can temporarily increase the permeability of the cell membrane, allowing small molecules to enter. H101 virus is an oncolytic adenovirus with deleted E1B-55kD and E3 regions that selectively targets and kills tumor cells. This study aimed to investigate whether the H101 oncolytic virus can serve as a supplementary therapeutic approach to kill tumors combined with RE.</p><p><strong>Methods: </strong>We first explored how RE and the H101 oncolytic virus, both individually and together, affected tumor cell proliferation and migration in cellular experiments. Subsequent <i>in vitro</i> studies further assessed the effects of different treatments on tumor growth. To understand the mechanisms of pathway changes in tumors from different treatment groups, we analyzed tumor samples from each group using bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq). Additional biochemical techniques were used to validate key molecular changes.</p><p><strong>Results: </strong>The combination of RE with the H101 oncolytic virus effectively inhibited pancreatic cancer cell proliferation and migration. Experiments using mouse subcutaneous tumor models confirmed that the combination therapy significantly reduced tumor growth. Further analysis bulk RNA-seq and scRNA-seq revealed that this combined approach activates the JNK-MAPK pathway, inducing apoptosis and enhancing therapeutic effects.</p><p><strong>Conclusions: </strong>This combination boosts therapeutic effectiveness by activating the JNK-MAPK pathway and promoting tumor cell apoptosis. These findings suggest that the H101 oncolytic virus could serve as a valuable adjunct to improve the efficacy of IRE treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1546242"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional insights of an uncommon hypomorphic variant in <i>IL2RG</i> as a monogenic cause of CVID-like disease with antibody deficiency and T CD4 lymphopenia.","authors":"Andrea González-Torbay, Keren Reche-Yebra, Álvaro Clemente-Bernal, Yolanda Soto Serrano, Luz Yadira Bravo-Gallego, Almudena Fernández López, Rebeca Rodríguez-Pena, María Bravo García-Morato, Eduardo López-Granados, Lucía Del Pino-Molina","doi":"10.3389/fimmu.2025.1544863","DOIUrl":"10.3389/fimmu.2025.1544863","url":null,"abstract":"<p><strong>Background: </strong>Over the last decade, the identification of hypomorphic variants in patients previously diagnosed with Common Variable Immunodeficiency (CVID) has led to the association of milder phenotypes with variants of the <i>IL2RG</i> gene that are usually related to severe combined immunodeficiency. Indeed, several revertant mosaicisms have been described in cases with hypomorphic variants in that gene. Our main objective herein was the functional characterization of p. (Pro58Thr) variant in the <i>IL2RG</i> gene in an adult patient with antibody deficiency and moderate CD4⁺ T cell lymphopenia.</p><p><strong>Methods: </strong>Evaluation of the patient included a clinical examination and a complete analysis of the peripheral blood phenotype. To further explore <i>IL2RG</i> functionality we selected downstream signaling readouts, namely STAT3 and STAT5 phosphorylation, NK degranulation and B- and T-cell proliferation capacity <i>in vitro</i>, which can be measured by flow cytometry, that reflect the strength of homeostatic signaling pathways in resting cells and after activation.</p><p><strong>Results: </strong>The patient presented reduced CD132 expression and conserved T- and B-cell proliferation capacity <i>in vitro</i>. However, we found that intracellular signaling downstream of IL2γc is affected, with reduced STAT3 phosphorylation after IL-21 stimulation in B cells and CD4 T cells. In addition, CD4⁺ T cells showed a reduced STAT5 phosphorylation in response to IL-2, which was not so evident in CD8⁺ T cells. NK degranulation was impaired upon PHA and IL-2 as well as plasmablast differentiation <i>in vitro</i>.</p><p><strong>Conclusion: </strong>We conclude that p. (Pro58Thr) in the <i>IL2RG</i> gene is functionally a hypomorphic variant, as reported previously. Although the functionality of CD8⁺ is less impaired than the rest of the lymphocyte subsets, we did not detect a reversion of the variant in isolated CD8⁺, CD4⁺, CD19⁺ or NK cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1544863"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TPL2 kinase activity is required for <i>Il1b</i> transcription during LPS priming but dispensable for NLRP3 inflammasome activation.","authors":"Denise L Fahey, Niki Patel, Wendy T Watford","doi":"10.3389/fimmu.2025.1496613","DOIUrl":"10.3389/fimmu.2025.1496613","url":null,"abstract":"<p><p>The NLRP3 inflammasome complex is an important mechanism for regulating the release of pro-inflammatory cytokines, IL-1β and IL-18, in response to harmful pathogens. Overproduction of pro-inflammatory cytokines has been linked to cryopyrin-associated periodic syndrome, arthritis, and other inflammatory conditions. It has been previously shown that tumor progression locus 2, a serine-threonine kinase, promotes IL-1β synthesis in response to LPS stimulation; however, whether TPL2 kinase activity is required during inflammasome priming to promote <i>Il1b</i> mRNA transcription and/or during inflammasome activation for IL-1β secretion remained unknown. In addition, whether elevated type I interferons, a consequence of either <i>Tpl2</i> genetic ablation or inhibition of TPL2 kinase activity, decreases IL-1β expression or inflammasome function has not been explored. Using LPS-stimulated primary murine bone marrow-derived macrophages, we determined that TPL2 kinase activity is required for transcription of <i>Il1b</i>, but not <i>Nlrp3</i>, <i>Il18</i>, caspase-1 (<i>Casp1</i>), or gasdermin-D (<i>Gsdmd</i>) during inflammasome priming. Both <i>Casp1</i> and <i>Gsdmd</i> mRNA synthesis decreased in the absence of type I interferon signaling, evidence of crosstalk between type I interferons and the inflammasome. Our results demonstrate that TPL2 kinase activity is differentially required for the expression of inflammasome precursor cytokines and components but is dispensable for inflammasome activation. These data provide the foundation for the further exploration of TPL2 kinase inhibitor as a potential therapeutic in inflammatory diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1496613"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Spatial immunology of tissue microenvironments.","authors":"Roslyn A Kemp, Felix Marsh-Wakefield","doi":"10.3389/fimmu.2025.1584850","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1584850","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1584850"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Porphyromonas gingivalis</i> exacerbates experimental autoimmune encephalomyelitis by driving Th1 differentiation via ZAP70/NF-κB signaling.","authors":"Dong Dai, Guoqin Cao, Shengyuan Huang, Min Xu, Jilei Wang, Xue Han, Qiuying Ma, Jiang Lin","doi":"10.3389/fimmu.2025.1549102","DOIUrl":"10.3389/fimmu.2025.1549102","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is characterized by chronic inflammation and demyelination within the central nervous system (CNS), primarily driven by the abnormal activation of the peripheral immune system, notably Th1 cells. As the principal pathogen in periodontitis, <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) is linked to an increased risk of multiple sclerosis progression; however, its role in central nervous system inflammation remains unclear. In this study, we aimed to determine whether <i>P. gingivalis</i> promotes peripheral Th1 cell differentiation via the ZAP70/NF-κB signaling pathway, thereby exacerbating experimental autoimmune encephalomyelitis(EAE), a model of multiple sclerosis.</p><p><strong>Methods: </strong>C57BL/6J mice were randomly divided into healthy control, periodontitis, EAE, and periodontitis with EAE group. Neurological function was assessed using Weaver's score. Histopathology (H&E, LFB staining) and Evans blue dye leakage evaluated inflammation, demyelination, and blood-brain barrier(BBB)permeability. Th1 and Th17 cells were quantified by flow cytometry, while immunofluorescence staining was performed to analyze Claudin-5, IFN-γ ⁺CD4⁺ T -positive cell and IL-17⁺CD4⁺-positive cell expression. Western blotting measured NF-κB and related protein expression. Reference-based mRNA sequencing analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment was conducted to identify differential gene expression and pathway enrichment.</p><p><strong>Results: </strong>In mice with experimental autoimmune encephalomyelitis, <i>P. gingivalis</i> infection significantly elevated Th1 cell proportions in the peripheral blood, increased interferon-gamma expression, and exacerbated central nervous system inflammation and demyelination by enhancing blood-brain barrier permeability. The infection also activated the ZAP70/NF-κB pathway, essential for peripheral Th1 differentiation, as evidenced by p65 nuclear translocation and significant upregulation of Th1-related genes, including those of the transcription factor <i>Tbx21</i> and interleukin-12 receptors. <i>In vitro</i>, <i>P. gingivalis</i> lipopolysaccharide (LPS) stimulated Th1 differentiation via ZAP70/NF-κB, which was effectively blocked by pathway inhibitors, reducing Th1 cells and pro-inflammatory factors.</p><p><strong>Discussion: </strong>Our findings elucidate, for the first time, how <i>P. gingivalis</i> infection promotes central nervous system inflammation by driving Th1 cell differentiation via peripheral ZAP70/NF-κB pathway activation. This highlights <i>P. gingivalis</i> as a local periodontitis pathogen and significant contributor to neuroinflammation, providing new insights into the pathogenesis of multiple sclerosis and identifying promising targets for immunomodulatory therapeutic strategies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1549102"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and characterization of immunopeptides isolated from pig spleen and evaluation of their immunomodulatory properties <i>in vitro</i> and <i>in vivo</i>.","authors":"Minhao Xia, Chong Ling, Hui Ye, Shujie Liang, Qingyun Cao, Weiwei Wang, Changming Zhang, Zemin Dong, Min Tian, Jianjun Zuo, Yongwen Zhu","doi":"10.3389/fimmu.2025.1544299","DOIUrl":"10.3389/fimmu.2025.1544299","url":null,"abstract":"<p><p>The importance of small bioactive peptides derived from pig spleen have been used to enhance immune responses and support intestinal health. However, there is a lack of information regarding the conformational relationship and their effects on immune function of pig spleen proteins (PSPs). The objective of this study was to prepare and assess the immunomodulatory characteristics of immunopeptides from PSP. Firstly, enzymatic hydrolysates from PSP were prepared using alkaline protease and aminopeptidase, and small hydrolysate fractions with a <3 kDa were separated by SDS-PAGE and GPC. The bioactive peptides were then identified at peaks 5 to 7 (PSP-5, 6 and 7) by HPLC and TOF-MS, which were mainly composed of Pro-Glu-Leu by LC-MS. The PSP-5 and PSP-6 pronounced greater beneficial effects on cell viability and nitric oxide (NO) production than PSP-7 in macrophage, and PSP-5 exhibited a higher immunomodulatory ability than PSP-6. <i>In vivo</i>, the oral administration of 25-50 mg PSP-5/kg body weight (BW) protected against cyclophosphamide (CTX)-induced immunosuppression in spleen and intestine of mouse, as evidenced by increased cytokine and sIgA productions. In conclusion, a novel set of bioactive immunopeptides derived from PSP through enzymatic hydrolysis could enhance immunomodulatory properties.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1544299"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis: retrospective analysis based on case reports.","authors":"Ronghui Li, Haibo Lei, Chunjiang Wang, Xiang Liu","doi":"10.3389/fimmu.2025.1563100","DOIUrl":"10.3389/fimmu.2025.1563100","url":null,"abstract":"<p><strong>Background: </strong>Stevens - Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening adverse reaction to nivolumab. This study investigated the clinical features of nivolumab induced SJS/TEN to provide evidence for diagnosis and treatment.</p><p><strong>Methods: </strong>Relevant articles on nivolumab induced SJS/TEN published before December 31, 2024 were collected by searching the database, and then extracting the data for summary analysis.</p><p><strong>Results: </strong>Thirty-one patients were enrolled with a median age of 65 years (range 43, 86). SJS/TEN appear at a median of 5.5 weeks (range, 0.9 108). Bullae/blisters (64.5%), erythema (54.8%), skin rash (54.8%), epidermal detachment (29.0%) and pain (29.0%) were the main skin symptoms. Skin biopsy showed epidermal necrosis (41.9%), keratinocytic necrosis (38.7%), interface dermatitis (29.0%) and inflammatory cell infiltration (45.2%). After stopping nivolumab and receiving treatment, 74.2% of the patients had improvement in skin symptoms, and 22.6% of the patients died of TEN.</p><p><strong>Conclusion: </strong>As a rare immune-related adverse event of nivolumab, SJS/TEN should be closely monitored during the treatment. Nivolumab induced SJS/TEN has a long incubation period, serious clinical symptoms and poor prognosis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563100"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour necrosis factor-α induces macromolecule translocation in HIV-derived duodenal organoids.","authors":"Kopano Valerie Masete, Alain S Massarani, Jörg-Dieter Schulzke, Hans-Jörg Epple, Nina A Hering","doi":"10.3389/fimmu.2025.1563702","DOIUrl":"10.3389/fimmu.2025.1563702","url":null,"abstract":"<p><strong>Background: </strong>Disease progression from human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) is marked by chronic immune activation, partly due to increased translocation of gut-derived microbial antigens. Elevated mucosal tumour necrosis factor-α (TNF-α) and resulting epithelial cell apoptosis may be the etiology. However, studies using carcinoma cell lines have failed to find a causal link, possibly due to cellular abnormalities related to the malignant transformation of these immortal cell lines.</p><p><strong>Methods: </strong>We established intestinal organoid monolayers from healthy controls and HIV-infected adults and characterized their growth dynamics and cellular composition. We then examined the effects of HIV-associated cytokines on transepithelial resistance (TER), apoptosis and macromolecule translocation.</p><p><strong>Results: </strong>Organoid monolayers from HIV-infected patients grew similarly to healthy controls, forming confluent monolayers within one to two weeks containing enterocytes, Paneth, goblet and stem cells. IFN-γ synergized with TNF-α, allowing TNF-α to cause caspase-mediated apoptosis and TER reduction within 5 ± 3 hours, reflecting patient sample heterogeneity. This led to paracellular passage of 4 kDa Dextran and transcytosis of 44 kDa horse radish peroxidase, both of which could be blocked by pan-caspase inhibitor, Q-VD-Oph.</p><p><strong>Conclusion: </strong>Our study confirms that intestinal organoid monolayers from biopsies of HIV-infected individuals can be used to study apoptosis-related epithelial barrier dysfunction and macromolecular translocation. We provide direct evidence that TNF-α-induced apoptosis triggered two pathways of macromolecular translocation: paracellular passage via apoptotic leaks and transcytosis. Therapies targeting apoptosis may be useful in preventing disease progression from HIV to AIDS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563702"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A secreted Tapasin isoform impairs cytotoxic T lymphocyte recognition by disrupting exogenous MHC class I antigen presentation.","authors":"Robyn P Seipp, Guillaume Hoeffel, Alexander R Moise, Siri Lok, Anne-Claire Ripoche, Concepción Marañón, Anne Hosmalin, Wilfred A Jefferies","doi":"10.3389/fimmu.2024.1525136","DOIUrl":"10.3389/fimmu.2024.1525136","url":null,"abstract":"<p><p>Endogenous and exogenous antigen processing and presentation through the MHC class I peptide-loading complex (PLC) are essential for initiating cytotoxic T lymphocyte responses against pathogens and tumors. Tapasin, a key component of the PLC, is produced in multiple isoforms through alternative splicing, each isoform influencing the assembly and stability of MHC class I molecules differently. While the canonical Tapasin isoform plays a critical role in stabilizing MHC class I by facilitating optimal peptide loading in the endoplasmic reticulum (ER), the other isoforms function in distinct ways that impact immune regulation. This study aimed to investigate the role of Tapasin isoforms, particularly soluble isoform 3, in modulating antigen presentation and immune responses, focusing on their effects on MHC class I peptide loading and surface expression. Our findings show that isoforms 1 and 2 stabilize TAP and facilitate efficient peptide loading onto MHC class I in the ER, promoting optimal antigen presentation. In contrast, isoform 3, which lacks both the ER retention signal and the transmembrane domain, is secreted and acts as a negative regulator. Isoform 3 inhibits the loading of exogenous peptides onto MHC class I molecules at the cell surface, thereby playing a critical role in the spatial and temporal regulation of MHC class I antigen presentation. The secreted Tapasin isoform 3 likely regulates immune responses by preventing inappropriate T cell activation and cytotoxicity, which could otherwise lead to immune-mediated tissue damage and contribute to autoimmune disorders. Understanding the distinct functions of Tapasin isoforms provides insights into immune regulation and highlights the importance of fine-tuning peptide-loading processes to ensure proper immune responses and prevent immune-related pathologies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"15 ","pages":"1525136"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: A refractory unusual tetrad of overlap syndrome involving rheumatoid arthritis, Sjögren's syndrome, autoimmune hepatitis, and type 1 renal tubular acidosis, successfully treated with a BLyS/APRIL dual inhibitor.","authors":"Wenjing Wang, Xin Ma, Bei Zhang, Zhibo Zhang, Xinfeng Wu, Hongwei Jiang, Xiaofei Shi","doi":"10.3389/fimmu.2025.1558059","DOIUrl":"10.3389/fimmu.2025.1558059","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) and Sjögren's syndrome (SS) are systemic autoimmune conditions. SS frequently occurs associated with RA. In patients with RA, those with SS exhibit a higher disease burden, increased disease activity, and more complex comorbidities compared with those without SS.</p><p><strong>Case report: </strong>We report a 54-year-old female patient who was previously diagnosed with early-stage RA less than 1 year ago. She was subsequently confirmed to have SS associated with RA. Additionally, she developed multiple autoimmune comorbidities, including autoimmune hepatitis and type 1 renal tubular acidosis. The patient resisted various treatments, including immunosuppressive drugs, disease-modifying antirheumatic drugs, and anti-inflammatory small-molecule drugs. This was evidenced by poor DA28 responses, persistent laboratory abnormalities, and ongoing symptoms and signs. Finally, she responded well to Telitacicept, a BLyS/APRIL dual inhibitor.</p><p><strong>Discussion: </strong>Even in the early stage, multiple autoimmune comorbidities can exhibit high levels of disease activity and may not respond to conventional therapies. Telitacicept, the first dual inhibitor of BLyS/APRIL, has the potential to provide significant efficacy and safety for RA patients who also have overlapping SS and other autoimmune diseases that do not respond to standard treatments. The limitations included the absence of a liver biopsy and the short follow-up period.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1558059"},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}