Maedeh Nikzad-Chaleshtori, Mohsen Asgari, Golnoosh Rezaeizadeh, Faranak Aali, Abbas Doosti
{"title":"The urease E subunit vaccine stimulate the immune response versus Helicobacter pylori in animal model.","authors":"Maedeh Nikzad-Chaleshtori, Mohsen Asgari, Golnoosh Rezaeizadeh, Faranak Aali, Abbas Doosti","doi":"10.1007/s12026-025-09625-6","DOIUrl":"https://doi.org/10.1007/s12026-025-09625-6","url":null,"abstract":"<p><p>There is a strong association between Helicobacter pylori (H. pylori) and the occurrence of gastritis and gastric mucosal lymphoma in the human population. Vaccination is a viable preventive measure in light of the escalating issue of antibiotic resistance. The use of DNA vaccines presents a potentially effective approach. This study used the utilization of antigenic H. pylori urease E subunit (UreE) for the development of a DNA vaccine. The UreE gene was chemically cloned into pIRES2-DsRed-Express (pDNA), and PCR and restriction enzyme digestion verified the cloning. The immunogenicity and immune-protective efficacy of the vaccination were assessed in BALB/c mice. In contrast, blood samples from BALB/c mice inoculated with pDNA-UreE showed higher levels of IgG, IFN-γ, IL- 4, and IL- 17. Furthermore, stomach damage and bacterial loads were reduced, and BALB/c mice inoculated with pDNA-UreE exhibited a significant protection rate (87.5%) against the H. pylori challenge. pDNA-UreE generated a combination of Th1-Th2-Th17 immune responses, perhaps contributing to adequate protection. Based on our findings, using this DNA immunization as a preventive measure against H. pylori infection is a viable approach.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"74"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014778","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}
Begüm Rana Atalay, Ömer Mete Başkan, Semanur Ercan, Ece Aydın, Furkan Ayaz, Esra Aydemir
{"title":"Immunomodulatory effects of alexidine dihydrochloride on mammalian macrophages through the modulation of the JNK pathway.","authors":"Begüm Rana Atalay, Ömer Mete Başkan, Semanur Ercan, Ece Aydın, Furkan Ayaz, Esra Aydemir","doi":"10.1007/s12026-025-09631-8","DOIUrl":"https://doi.org/10.1007/s12026-025-09631-8","url":null,"abstract":"<p><p>A plethora of the cancer drugs with high therapeutic potential cannot pass the clinical trials because of their immunotoxic activities. In this study, we tested the immunomodulatory and immunostimulatory effects of the anticancer agent alexidine dihydrochloride on J774.2 macrophage cell lines in vitro. The production levels of the pro-inflammatory cytokines (TNF-α, IL-6, GM-CSF, IL-12p40) were measured and compared by ELISA method. The activated (phosphorylated) JNK protein levels were measured by flow cytometer and the possible related intracellular signaling pathway was examined in this way. According to our results, alexidine dihydrochloride has an anti-inflammatory effect on the LPS-stimulated macrophage cell lines, as evidenced by reduced cytokine production compared to controls. Furthermore, its intracellular mechanism of action was found to be mediated partially through JNK signaling pathways. These findings suggest that alexidine dihydrochloride, while being an effective anticancer agent, may also modulate immune responses by dampening excessive inflammation. In this study, determining the anti-inflammatory effect of alexidine dihydrochloride on the immune system will seriously shed light on the role of this anticancer agent in future clinical studies and will provide a serious basis. In summary, the effects of the most drug-active ingredients on the inflammatory response in immune system cells have not been fully tested, and this creates the problem of many drugs failing in clinical studies or lack of knowledge on their side effects. Our study aimed to determine the effect of alexidine dihydrochloride, used as an anticancer agent, on the inflammatory response in J774.2 macrophage cell lines. Future studies with more immune system cells and a wider analysis of the intracellular signaling pathways will be informative about the immunotoxicity of the drug molecule. Future research involving a broader range of immune cell types and a more comprehensive analysis of intracellular signaling pathways will help clarify the immunotoxicity profile of this anticancer agent.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"73"},"PeriodicalIF":3.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994519","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}
Xuemei Liu, Ai Luo, Mei Yang, Jian Luo, Huifang Li, Xiaoting Chen, Bing Mao, Hongli Jiang, Wei Liu
{"title":"Baicalin restores innate lymphoid immune imbalance during exacerbation of COPD.","authors":"Xuemei Liu, Ai Luo, Mei Yang, Jian Luo, Huifang Li, Xiaoting Chen, Bing Mao, Hongli Jiang, Wei Liu","doi":"10.1007/s12026-025-09629-2","DOIUrl":"https://doi.org/10.1007/s12026-025-09629-2","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is characterized by immune dysregulation, including altered innate lymphoid cell (ILC) immune responses, particularly during exacerbations (ECOPD). Baicalin, a natural compound prevalent in various herbal medicines, has shown promise as a therapeutic candidate in ECOPD. However, its potential and molecular mechanism for addressing ILC immune imbalance during ECOPD remain poorly understood. First, this study conducted a cross-sectional analysis of ILC immune responses in stable COPD patients and those experiencing exacerbations. Then, clinical findings of skewed ILC immunity were validated in cigarette smoke and lipopolysaccharide-induced ECOPD mouse models. Lastly, the therapeutic effect of baicalin on restoring ILC immune homeostasis was investigated in experimental ECOPD mouse models. Significant downregulation of ILC2 immunity was observed during COPD exacerbations, accompanied by increased ILC1 and ILC3 responses, particularly in cases associated with bacterial infections. Notably, elevated IL-22 levels were observed in this group. Administration of recombinant IL-22 in ECOPD mouse models disrupted lung ILC homeostasis, specifically inhibiting the accumulation of ILC2. Proteomics and transcriptomics analyses suggested IL-22 as a mediator of type 2 immune suppression by creating a molecular environment that favors type 1 and type 3 immunity. Treatment with baicalin effectively restored ILC2 immunity by enhancing the recruitment and activation of lung ILC2 while suppressing ILC1 and ILC3 responses. Importantly, baicalin attenuated IL-22 production from lung ILC3, highlighting its potential as an IL-22 inhibitor. Baicalin demonstrates potential as a therapeutic strategy for addressing ILC immune imbalance in COPD exacerbations, particularly by restoring ILC2 immunity and partially inhibiting IL-22 production. Clinical registration The cross-sectional study was registered with the Chinese Clinical Trial Registry (ChiCTR2100050683).</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"71"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998542","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}
Serdar Goktas, Gamze Sonmez, Ali Şahin, Nadira Nabiyeva Çevik, Canan Caka, Ismail Yaz, Saliha Esenboga, Deniz Cagdas
{"title":"A patient with RFX5 variant causing an expression defect in both HLA ABC and HLA DR.","authors":"Serdar Goktas, Gamze Sonmez, Ali Şahin, Nadira Nabiyeva Çevik, Canan Caka, Ismail Yaz, Saliha Esenboga, Deniz Cagdas","doi":"10.1007/s12026-025-09627-4","DOIUrl":"https://doi.org/10.1007/s12026-025-09627-4","url":null,"abstract":"<p><p>The major histocompatibility complex (MHC) encompasses a group of genes critical for immune system regulation. In humans, these molecules are referred to as human leukocyte antigens (HLA) due to their initial discovery in human leukocytes. Class I molecules present antigens to CD8 + T cells, while Class II molecules present to CD4 + T cells. Here we report a patient who had a background of parental consanguinity and a family history suggestive of immunodeficiency. He presented with clinical symptoms including fever, septic arthritis, recurrent moniliasis. Preliminary diagnostic tests revealed hypogammaglobulinemia and CD4 lymphopenia. Further immunological assessment indicated extremely low expression levels of HLA molecules: HLA ABC at 5% and HLA DR at 0%. Genetic analysis showed a mutation in the regulatory factor X5 (RFX5) gene, leading to a combined immunodeficiency diagnosis. Consequently, hematopoietic stem cell transplantation (HSCT) was planned. Regulatory factor X5plays a pivotal role in immune function by transactivating genes critical for the expression of MHC Class I and Class II molecules, as well as beta- 2-microglobulin (B2M). MHC Class I transcription is controlled indirectly by RFX5, and the RFX5 gene mutation in the patient likely caused the markedly reduced expression of HLA ABC in addition to HLA DR. Combined HLA-ABC and HLA-DR expression analyses via flow cytometry may serve as a valuable diagnostic tool for identifying RFX5-related immunodeficiency at an early stage, facilitating timely genetic testing and appropriate clinical management.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"72"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984768","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":"Comparison of artificial intelligence applications and commercial system performances using selected ANA IIF images.","authors":"Mehmet Akif Durmuş, Selda Kömeç","doi":"10.1007/s12026-025-09623-8","DOIUrl":"https://doi.org/10.1007/s12026-025-09623-8","url":null,"abstract":"<p><p>Accurate and accessible classification of anti-nuclear antibodies (ANA) through indirect immunofluorescence (IIF) imaging is crucial for diagnosing autoimmune diseases. However, many laboratories, particularly those with limited resources, lack access to expensive commercial systems for automated analysis. This study evaluates the performance of an application developed by expert physicians using an artificial intelligence application (Microsoft Azure) to classify ANA IIF images. The results are compared with EuroPattern to assess the potential of AI in assisting laboratory experts, especially in resource-limited settings. A total of 648 ANA IIF images from the EuroPattern archive were used to train an AI model across nine classes with varying fluorescence intensities (+ to + + + +). Testing was conducted with 96 images, ensuring clarity by excluding mixed patterns. Microsoft Azure's Custom Vision service was employed for labeling and prediction. Expert evaluations, EuroPattern results, and AI classifications were compared. Both EuroPattern and the Azure-based AI model achieved 100% sensitivity, specificity, and accuracy in positive and negative discrimination. EuroPattern had an intraclass correlation coefficient (ICC) of 0.979, and the Azure-based AI model had an ICC of 0.948, indicating slightly lower performance. EuroPattern outperformed the Azure-based AI model in recognizing homogeneous, speckled, centromere, and dense fine-speckled patterns. The Azure-based AI model performed better in identifying cytoplasmic reticular/AMA-like patterns. The results suggest that AI-based image analysis tools, such as Azure, can be valuable for diagnostics in resource-limited labs. However, further testing with larger datasets and routine patient samples is needed to confirm their effectiveness in real-world clinical settings.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"70"},"PeriodicalIF":3.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984807","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}
Bintao Su, Quanhong Zhang, Xianyong Hu, Bo Xie, Chao Chen, Yan Zhao, Zhi Liu, Ling Ma, Jinbo Chen
{"title":"Role of basophils and type 2 inflammation in bullous pemphigoid pathophysiology: a comparative study of blood and blister fluid.","authors":"Bintao Su, Quanhong Zhang, Xianyong Hu, Bo Xie, Chao Chen, Yan Zhao, Zhi Liu, Ling Ma, Jinbo Chen","doi":"10.1007/s12026-025-09617-6","DOIUrl":"https://doi.org/10.1007/s12026-025-09617-6","url":null,"abstract":"<p><p>Bullous pemphigoid (BP) is an autoimmune disease characterized by blister formation and inflammatory cell infiltration. In addition to eosinophil and neutrophil infiltration, there are many other inflammatory cells and factors involved in the pathophysiology of BP. Elucidating the inflammation environment will help to the diagnosis and treatment of BP. We used flow cytometry and wright-stained smears to analyze immune cells, and cytometric bead array methods were used to analyze immune factors in matched blood and blister fluid. Besides abundant eosinophil and neutrophil accumulation, distinct basophil infiltration was detected in blister fluid of patients with BP. We also found significant CD4<sup>+</sup> T lymphocyte activation and increased type 2 cytokine secretion in BP blister fluid. Under no stimulation, basophils produce more IL-4 compared to CD4<sup>+</sup> T lymphocytes in BP blister fluid. Basophils might play a more important role in BP than we early thought. Along with other inflammatory cells and factors, basophils, demonstrated as one of the main producers of IL-4, orchestrate the type 2 inflammation environment in BP.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"68"},"PeriodicalIF":3.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811267","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":"HBx/WDR5 enhances IGF-1 transcription in hepatocellular carcinoma cells and promotes recruitment, infiltration, and activity of Treg cells.","authors":"Erli Wang, Shuhua Sun, Hui Li, Yi Jia, Zhe Bai","doi":"10.1007/s12026-025-09620-x","DOIUrl":"10.1007/s12026-025-09620-x","url":null,"abstract":"<p><p>HBV X protein (HBx), the smallest open reading frame in the hepatitis B virus (HBV) genome, can promote hepatocellular carcinoma (HCC) tumorigenesis by activating the expression of multiple oncogenes through inducing epigenetic alterations and interacting with the underlying transcriptional machinery. HBV non-infected HepG2 and Huh7 cells were transfected with HBx expression plasmids. The transcriptional, protein expression, and secretion levels of IGF-1 were detected by RT-qPCR, western blot, and ELISA, respectively. ChIP-qPCR was used to analyze the binding proteins on the IGF-1 gene. A co-culture system of HCC and Treg cells was designed using Transwell chambers. IGF-1 mRNA, protein, and secretion levels were increased in HepG2 and Huh7 cells exogenously expressing HBx. HBx was able to enter the nucleus and interact with the enhancer region of the IGF-1 gene. Levels of WDR5 and H3K4me1, which bind to the enhancer region of the IGF-1 gene, were also increased in HepG2 and Huh7 cells ectopically expressing HBx. Knockdown of WDR5 counteracted the upregulation of IGF-1 mRNA and protein levels by HBx. In the cell co-culture system, HBx/IGF-1 signaling in HCC cells promoted Treg cells expansion, IL-10 secretion, and infiltration, which was blocked by the IGF-1R inhibitor picropodophyllin. HBx/WDR5 promoted IGF-1 transcription in HCC cells through enhancers. HBx could promote Treg cell recruitment, infiltration, and activity by enhancing IGF-1 expression. IGF-1/IGF-1R signaling plays an important role in the communication between HCC cells and Treg cells. Targeting WDR or IGF-1/IGF-1R would be beneficial for the treatment of HCC.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"69"},"PeriodicalIF":3.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811266","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":"Phenotypic characterization of tumor associated macrophages and circulating monocytes in patients with Urothelial carcinoma of bladder.","authors":"Aishwarya Singh, David Raja, Seema Kaushal, Amlesh Seth, Prabhjot Singh, Alpana Sharma","doi":"10.1007/s12026-025-09624-7","DOIUrl":"https://doi.org/10.1007/s12026-025-09624-7","url":null,"abstract":"<p><strong>Objectives: </strong>Targeting immune checkpoints has shown clinical efficacy in Urothelial carcinoma of bladder (UBC); however, a substantial percentage of patients remains unresponsive, which warrants the elucidation of novel therapeutic targets to circumvent immune suppression. Tumor associated macrophages (TAMs) are known for their indispensable role in cancer immunosuppression however, their phenotype and functionality in UBC is not yet clear.</p><p><strong>Materials and methods: </strong>Phenotypic composition and functional markers of TAMs, and circulating monocytes were assessed in surgically resected bladder tumors and PBMC of UBC patients (n = 40). Besides, 40 healthy volunteers were recruited to draw comparisons for peripheral monocytes. Monocytes from patients were treated with autologous bladder tumor conditioned media (TCM) to assess its effects on macrophage-based markers.</p><p><strong>Results: </strong>The infiltration of TAMs was significantly increased in bladder tumor tissue by 21.2% and which displayed both M1 and M2 phenotypic markers, wherein M2 phenotype exhibited positive correlation with disease severity. Circulating monocytes exhibited an increase in frequency of non-classical monocytes by 17.42% and elevated M2-macrophage markers by 20%. Further, TAMs and circulating monocytes exhibits an elevated expression of IL- 10 and inhibitory immune checkpoints (PD-1, PD-L1, and B7-H4). Stimulation of patient-derived monocytes with TCM further augmented the expression of immune checkpoints, and immunosuppressive markers like IL-10, TGF-β and CX3CR- 1. Lastly, M2 phenotype of TAMs and PD-L1+ and B7-H4 + TAMs displayed positive correlation with clinico-pathological parameters in UBC patients.</p><p><strong>Conclusion: </strong>This study presents TAMs with an immunosuppressive phenotype that correlates positively with disease severity and suggests TAMs as a potential therapeutic candidate to restore the anti-tumor immunity in UBC.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"66"},"PeriodicalIF":3.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803127","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 management of autoimmune liver diseases: juncture, opportunities, and challenges ahead.","authors":"Yangfan Chen, Ruofei Chen, Haiyan Li, Zongwen Shuai","doi":"10.1007/s12026-025-09622-9","DOIUrl":"10.1007/s12026-025-09622-9","url":null,"abstract":"<p><p>The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunological tolerance, which leads to an inflammatory process that causes liver damage.The self-attack is started by T-helper cell-mediated identification of liver autoantigens and B-cell production of autoantibodies,and it is maintained by a reduction in the number and activity of regulatory T-cells.Infections and environmental factors have been explored as triggering factors for these conditions, in addition to a genetic predisposition.Allelic mutations in the HLA locus have been linked to vulnerability, as have relationships with single nucleotide polymorphisms in non-HLA genes.Despite the advances in the management of these diseases, there is no curative treatment for these disorders, and a significant number of patients eventually progress to an end-stage liver disease requiring liver transplantation.In this line, tailored immune-therapeutics have emerged as possible treatments to control the disease.In addition, early diagnosis and treatment are pivotal for reducing the long-lasting effects of these conditions and their burden on quality of life.Herein we present a review of the etiology, clinical presentation, diagnosis, and challenges on ALDs and the feasible solutions for these complex diseases.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"67"},"PeriodicalIF":3.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803125","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}
Yang Chen, Min Shen, Yong Gu, Xinyu Xu, Lingling Bian, Fan Yang, Shuang Chen, Li Ji, Jin Liu, Jing Zhu, Zheng Zhang, Qi Fu, Yun Cai, Heng Chen, Kuanfeng Xu, Min Sun, Xuqin Zheng, Jie Shen, Hongwen Zhou, Mei Zhang, Kathryn Haskins, Liping Yu, Tao Yang, Yun Shi
{"title":"Pivotal epitopes for islet antigen-specific CD8<sup>+</sup> T cell detection improve classification of suspected type 1 diabetes with the HLA-A*0201 allele.","authors":"Yang Chen, Min Shen, Yong Gu, Xinyu Xu, Lingling Bian, Fan Yang, Shuang Chen, Li Ji, Jin Liu, Jing Zhu, Zheng Zhang, Qi Fu, Yun Cai, Heng Chen, Kuanfeng Xu, Min Sun, Xuqin Zheng, Jie Shen, Hongwen Zhou, Mei Zhang, Kathryn Haskins, Liping Yu, Tao Yang, Yun Shi","doi":"10.1007/s12026-025-09616-7","DOIUrl":"10.1007/s12026-025-09616-7","url":null,"abstract":"<p><p>A proportion of patients with new-onset diabetes share similar symptoms with type 1 diabetes (T1D) patients but they are negative for islet antigen-specific autoantibodies. This study was to develop an islet antigen-specific CD8<sup>+</sup> T-cell assay to provide autoimmune evidence regarding these \"suspected\" T1D patients. HLA-A*0201 individuals with autoAbs<sup>+</sup> T1D, autoAbs<sup>-</sup> suspected T1D, and type 2 diabetes, along with HLA-A*0201 healthy controls were recruited. Using interferon-γ enzyme-linked immunospot assays, the percentages of participants in each group with various islet antigen-specific CD8<sup>+</sup> T cells were determined. Sixteen out of the 28 islet antigen-specific epitopes tested were T1D specific, meaning that there was a significantly (P < 0.05) greater epitope positivity rate in the autoAbs<sup>+</sup> T1D cohort than in the healthy controls. Using a cutoff value of two positive epitopes, the 16-epitope panel led to a sensitivity of 75.0% and a specificity of 94.4% regarding the autoAbs<sup>+</sup> T1D patients. Even when using an optimized five-epitope panel, the results were highly accurate. Notably, in the application phase of the study, 77.8% of a new cohort of autoAbs<sup>-</sup> suspected T1D patients exhibited positivity when using the five-epitope optimized panel. This highly accurate method, especially for pediatric patients, will improve clinical diagnosis and etiological classification of autoimmune T1D.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"65"},"PeriodicalIF":3.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709747","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}