Immunologic Research最新文献

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Deciphering autoimmune susceptibility: a meta-analysis of PTPN22 gene variants.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-03-11 DOI: 10.1007/s12026-025-09614-9
Sheena Mariam Thomas, Ramakrishnan Veerabathiran
{"title":"Deciphering autoimmune susceptibility: a meta-analysis of PTPN22 gene variants.","authors":"Sheena Mariam Thomas, Ramakrishnan Veerabathiran","doi":"10.1007/s12026-025-09614-9","DOIUrl":"https://doi.org/10.1007/s12026-025-09614-9","url":null,"abstract":"<p><p>Autoimmune disorders are intricate conditions where the immune system directs its attack towards the body's tissues. The goal is to perform a thorough meta-analysis focusing on the genetic and epigenetic aspects of autoimmune disorders, specifically examining the role of the PTPN22 gene, particularly the rs2476601 variation, in influencing susceptibility to autoimmune diseases. The study followed PRISMA 2020 guidelines and PROSPERO registration and conducted a comprehensive meta-analysis to explore the association between PTPN22 gene variations and autoimmune disorders. Case-control studies presenting genotype information were included, and quantitative data analysis was performed using MetaGenyo software. The meta-analysis included 43 studies with 20,669 controls and 9,397 cases of autoimmune diseases, focusing on the PTPN22 gene rs2476601 polymorphism. Significant associations were observed between the PTPN22 polymorphisms across multiple genetic models, including allelic, dominant, and recessive models. However, no link was found between the over-dominant model. The obtained p-values were < 0.01 for the allele model (C vs T; OR: 0.63, 95% CI: 0.48-0.81, I<sup>2</sup> = 92%), 0.03 for the dominant model (CC + CT vs. TT; OR: 0.47, 95% CI: 0.24-0.95, I<sup>2</sup> = 87%), and < 0.01 for the recessive model (TT vs. CT + CC; OR: 0.61, 95% CI: 0.47-0.79, I<sup>2</sup> = 89%). However, the over-dominant model (CT vs. CC + TT; OR: 1.68, 95% CI: 1.32-2.15, I<sup>2</sup> = 86%) did not show a significant p-value (> 0.05). This meta-analysis emphasizes the significant impact of PTPN22 gene variations on autoimmune diseases, suggesting its potential as a biomarker for assessing risk and guiding targeted interventions.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"59"},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604749","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}
引用次数: 0
Echinocystic acid ameliorates ischemic acute kidney injury in neonatal rats by attenuating ferroptosis via the Nrf2/GPX4 pathway.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-03-11 DOI: 10.1007/s12026-025-09613-w
Xiaoping Dang, Qiong Zhang, Xun Jiang, Xiaojian Hu
{"title":"Echinocystic acid ameliorates ischemic acute kidney injury in neonatal rats by attenuating ferroptosis via the Nrf2/GPX4 pathway.","authors":"Xiaoping Dang, Qiong Zhang, Xun Jiang, Xiaojian Hu","doi":"10.1007/s12026-025-09613-w","DOIUrl":"https://doi.org/10.1007/s12026-025-09613-w","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is the most common complication in neonates with hypoxic-ischemic encephalopathy (HIE), significantly contributing to both morbidity and mortality, and targeting key pathological processes, such as inflammation, ferroptosis and apoptosis, could be an effective approach to improving survival outcomes in these patients. In this context, echinocystic acid (EA), a pentacyclic triterpene, has shown promising anti-inflammatory, antioxidant, and anti-apoptotic effects in various disease models, suggesting its potential as a therapeutic agent for AKI in HIE. To evaluate the therapeutic potential and underlying mechanisms of EA in ameliorating ischemia/reperfusion (IR)-induced AKI in neonatal rats. Seven-day-old neonatal rat pups were subjected to an IR injury model to induce AKI and treated with EA via intraperitoneal injection. The effects of EA on renal injury were assessed using western blotting, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescence, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) staining. Treatment with EA significantly reduced IR-induced renal pathology and injury scores, as well as serum levels of blood urea nitrogen (BUN) and creatinine (Cr). In addition, EA diminished the release of pro-inflammatory cytokines and reduced the levels of F4/80, a macrophage marker, in the IR-treated pups. EA also attenuated ferroptosis, as evidenced by decreased levels of iron (Fe<sup>2</sup>⁺), reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA), while simultaneously increasing the activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione (GSH). Furthermore, EA reduced apoptosis, as demonstrated by lower levels of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase (PARP). Mechanistically, EA activated the Nrf2/GPX4 pathway, and inhibition of Nrf2 with ML385 reversed EA's beneficial effects on ferroptosis, inflammation, and renal injury. EA may relieve ischemic AKI in neonatal rats by modulating inflammation, ferroptosis and apoptosis, through the activation of the Nrf2/GPX4 pathway, indicating that it could be a promising therapeutic agent for AKI in neonates.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"58"},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604750","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}
引用次数: 0
A comprehensive analysis of scRNA-Seq and RNA-Seq unveils B cell immune suppression in the AAV-loaded brain.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-03-05 DOI: 10.1007/s12026-025-09609-6
Shunyu Wu, Lu Xue, Xiang Li, Yaoxuan Wang, Yuting Zhu, Yuanbo Luo, Jiayu Sun, Tingting Jin, Wenying Shu, Zhaoyan Wang
{"title":"A comprehensive analysis of scRNA-Seq and RNA-Seq unveils B cell immune suppression in the AAV-loaded brain.","authors":"Shunyu Wu, Lu Xue, Xiang Li, Yaoxuan Wang, Yuting Zhu, Yuanbo Luo, Jiayu Sun, Tingting Jin, Wenying Shu, Zhaoyan Wang","doi":"10.1007/s12026-025-09609-6","DOIUrl":"10.1007/s12026-025-09609-6","url":null,"abstract":"<p><p>The use of AAV vectors for in vivo gene therapy has demonstrated the potential to permanently correct genetic diseases by delivering functional gene copies to the nuclei of affected tissues. AAV vectors, as tools for in vivo gene delivery, are particularly appealing and have shown safety and long-term efficacy in numerous organ-targeted experiments. Nevertheless, employing AAV vectors for gene therapy in the brain faces a notable hurdle in the shape of immune responses, chiefly instigated by the brain's resident immune cells, microglia. Additionally, lower levels of AAV vector-neutralizing antibodies have been detected in the cerebrospinal fluid compared to the circulatory system. This research, leveraging transcriptomic and single-cell RNA sequencing (scRNA-seq) data in conjunction with Mendelian randomization analysis, has identified the potential role of the XBP1 protein in mediating B-cell immunosuppression in the brain via the MDK-NCL ligand-receptor pair and associated genes. Furthermore, it paves the way for further investigation into the regulatory factors and pathways within the immune modulation network, as well as their prospective beneficial implications in immunotherapeutic treatments. By employing various innovative approaches, the study seeks to recreate the immune environment generated by AAV in the brain and preliminarily explore the immune suppression mechanisms induced by AAV vectors in the brain.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"57"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566986","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}
引用次数: 0
Concurrent infections in children with Kawasaki disease: lessons learned over 26 years.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-26 DOI: 10.1007/s12026-025-09607-8
Rakesh Kumar Pilania, Suprit Basu, Archan Sil, Sanjib Mondal, Abarna Thangaraj, Gayathri Cv, Manpreet Dhaliwal, Saniya Sharma, Ankur Kumar Jindal, Pandiarajan Vignesh, Sanjay Verma, Archana Angrup, Sanjeev H Naganur, Manphool Singhal, Amit Rawat, Deepti Suri, Surjit Singh
{"title":"Concurrent infections in children with Kawasaki disease: lessons learned over 26 years.","authors":"Rakesh Kumar Pilania, Suprit Basu, Archan Sil, Sanjib Mondal, Abarna Thangaraj, Gayathri Cv, Manpreet Dhaliwal, Saniya Sharma, Ankur Kumar Jindal, Pandiarajan Vignesh, Sanjay Verma, Archana Angrup, Sanjeev H Naganur, Manphool Singhal, Amit Rawat, Deepti Suri, Surjit Singh","doi":"10.1007/s12026-025-09607-8","DOIUrl":"https://doi.org/10.1007/s12026-025-09607-8","url":null,"abstract":"<p><p>Etiology of Kawasaki disease (KD) remains an enigma despite more than 50 years of extensive research. There is evidence that concurrent infections may play a role in the pathogenesis of KD. The present study reports various infections identified in a large cohort of patients with KD in Northwest India. We reviewed case records of patients with KD from January 1994 to February 2020. Patients with KD identified to have concurrent infection at presentation were analyzed in detail. Of 878 cases of KD during this period, 88 (60 boys, 28 girls; 64 incomplete KD, 24 complete KD) had evidence of concurrent infection. Infective manifestations included superficial and deep-seated abscesses (27.45%), pneumonia (28.4%), gastrointestinal manifestations (29.5%), urinary tract infection (4.5%), and septic arthritis (2.3%). Infectious agents were confirmed in 67/88 patients (76.13%) - these included bacteria (n = 51), viruses (n = 13), fungi (n = 2), and protozoa (n = 1). Among bacteria, infections with Staphylococcus sp. and Streptococcus sp. were the commonest (19/88 and 14/88 patients, respectively). Eighty-one children were treated with intravenous immunoglobulin (IVIg, 2 g/kg) and aspirin. Coronary artery abnormalities (CAAs) were seen in 11/88 patients (12.5%) during the acute phase - these normalized at 6 weeks of follow-up in all patients. To conclude, concurrent infections were seen in 10% of patients with KD at our center. If the clinical presentation suggests KD, one should not exclude the diagnosis even if there is evidence of an accompanying infection. Although 12.5% of patients with infection-associated KD had CAAs, none had persistent CAAs at 6 weeks of follow-up.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"56"},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500759","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}
引用次数: 0
Hepatitis C associated mixed cryoglobulinemia glomerulonephritis in the setting of undetectable viral load: successful treatment with hydroxychloroquine and review of the literature.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-21 DOI: 10.1007/s12026-025-09608-7
Faris Shweikeh, Yaritza Torres, Khadeja Khan, Mohamad Mouchli, Inderprit Singh
{"title":"Hepatitis C associated mixed cryoglobulinemia glomerulonephritis in the setting of undetectable viral load: successful treatment with hydroxychloroquine and review of the literature.","authors":"Faris Shweikeh, Yaritza Torres, Khadeja Khan, Mohamad Mouchli, Inderprit Singh","doi":"10.1007/s12026-025-09608-7","DOIUrl":"https://doi.org/10.1007/s12026-025-09608-7","url":null,"abstract":"<p><p>There are an estimated 58 million cases of Hepatitis C (HCV) worldwide. Approximately 38-76% of individuals can develop extrahepatic manifestations such as mixed cryoglobulinemia (MC). Importantly, the appearance of symptoms due to MC is linked by detectable HCV RNA. A 38-year-old male with remote history of HCV infection diagnosed 8 years prior presented to the emergency department with subacute renal failure with proteinuria, hematuria, and WBC/RBC casts. Biopsy confirmed acute proliferative, non-crescentic, inflammatory glomerulonephritis. He also had new onset cryoglobulinemia. His HCV RNA was low-grade and liver function tests were all within the normal range. A liver biopsy showed signs of chronic hepatitis with mildly active portal fibrosis. The MC was cleared with steroids and a re-measured HCV RNA quantitative was negative. Seven months later, he was readmitted with glomerulonephritis and elevated MC. However, the patient's HCV viral load was undetectable. The patient underwent 6 rounds of plasmapheresis and 6 doses of Rituximab were given with suppression of cryoglobulin to nil. A month later, the MC levels rose again, while the viral load remained undetectable with the possibility of spontaneous remission. After initiation of maintenance hydroxychloroquine, his GFR improved to normal over the next 2 years. Multiple theories have been suggested for the phenomenon including presence of residual virus and lymphoproliferation effects. Hydroxychloroquine could be a successful option, though future studies should corroborate our outcome.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"55"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467915","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}
引用次数: 0
A case of atypical infantile de novo antiphospholipid syndrome presenting with neonatal ischemic stroke without any triggering risk factors as a "second hit" and review of the literature.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-19 DOI: 10.1007/s12026-025-09605-w
Doruk Bor, Mustafa Vakur Bor
{"title":"A case of atypical infantile de novo antiphospholipid syndrome presenting with neonatal ischemic stroke without any triggering risk factors as a \"second hit\" and review of the literature.","authors":"Doruk Bor, Mustafa Vakur Bor","doi":"10.1007/s12026-025-09605-w","DOIUrl":"10.1007/s12026-025-09605-w","url":null,"abstract":"<p><p>Infantile antiphospholipid syndrome (APS) is a rare condition arising from either transplacental transfer of antiphospholipid antibodies (aPL) from the mother or de novo antibody production in the newborn. We present a unique case of cerebral artery thrombosis with persistently elevated anti-cardiolipin and anti-β2-glycoprotein-I antibodies, despite the absence of maternal aPL, suggesting primary de novo aPL synthesis. While the prevailing \"second-hit\" hypothesis suggests that additional thrombotic risk factors are required to trigger APS in infants, our case exhibited no prenatal, maternal, or thrombophilic risk factors. A literature review of 20 reported cases further confirmed that ours was the only case without additional thrombotic triggers among the 18 cases with complete data, challenging the necessity of a \"second hit\" in neonatal APS. Notably, aPL levels normalized over time without recurrence, raising questions about the need for long-term anticoagulation in select cases, including ours. These findings suggest a potential transient form of infantile APS and highlight the importance of sequential aPL testing to guide treatment. Further research is required to elucidate the mechanisms underlying de novo aPL synthesis and its clinical implications.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"53"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448839","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}
引用次数: 0
Lithospermic acid targeting heat shock protein 90 attenuates LPS-induced inflammatory response via NF-кB signalling pathway in BV2 microglial cells.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-19 DOI: 10.1007/s12026-025-09600-1
Jie Guo, Chen-Guang Li, Feng-Yi Mai, Jing-Rong Liang, Ze-Hao Chen, Jiao Luo, Ming-Chao Zhou, Yu-Long Wang, Wen-Tao Yang
{"title":"Lithospermic acid targeting heat shock protein 90 attenuates LPS-induced inflammatory response via NF-кB signalling pathway in BV2 microglial cells.","authors":"Jie Guo, Chen-Guang Li, Feng-Yi Mai, Jing-Rong Liang, Ze-Hao Chen, Jiao Luo, Ming-Chao Zhou, Yu-Long Wang, Wen-Tao Yang","doi":"10.1007/s12026-025-09600-1","DOIUrl":"10.1007/s12026-025-09600-1","url":null,"abstract":"<p><p>Microglia function as a vital constituent in the maintenance of brain homeostasis. Aberrant microglial activation, however, may contribute to neurodegenerative diseases. Lithospermic acid (LA) is a plant-derived polycyclic phenolic carboxylic acid isolated from Salvia miltiorrhiza. The present study investigated the potential effects of lithospermic acid on LPS-induced neuroinflammation in BV2 microglial cells and determined the mechanism of action of this compound. Cells were pre-treated with lithospermic acid for 1 h and incubated with LPS for 24 h. qPCR, immunofluorescence, and immunoblot assays were used to determine the expression of iNOS, COX2, NF-κB p65, and HSP90 expression. ELISA was employed to measure the production of pro-inflammatory cytokines. Lithospermic acid dramatically reduced LPS-stimulated cell migration and decreased NF-κB p65 nuclear translocation. Furthermore, lithospermic acid also markedly decreased the production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in a dose-dependent manner. Additionally, lithospermic acid inhibited NO and PGE2 production in response to LPS, and it also inhibited the expression of iNOS and COX2 in a dose-dependent manner. Molecular docking and experimental verification have demonstrated that lithospermic acid inhibits the activity and expression of HSP90. Small interfering RNA knockdown of HSP90 expression, which abrogated LPS-induced inflammation. These findings suggest that the lithospermic acid targeting HSP90 attenuates LPS-induced inflammatory response via the NF-κB signalling pathway in BV2 microglial cells. Collectively, lithospermic acid may offer therapeutic benefits for neurodegenerative disorders associated with microglial activation and could serve as a potential inhibitor/agent for the treatment of neuroinflammation.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"54"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448927","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}
引用次数: 0
Risk factors for predicting medium-giant coronary artery aneurysms in Kawasaki disease.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-17 DOI: 10.1007/s12026-025-09604-x
Li Zhao, Jiangping Wu, Xiaoliang Liu, Kaiyu Zhou, Yimin Hua, Shuran Shao, Chuan Wang
{"title":"Risk factors for predicting medium-giant coronary artery aneurysms in Kawasaki disease.","authors":"Li Zhao, Jiangping Wu, Xiaoliang Liu, Kaiyu Zhou, Yimin Hua, Shuran Shao, Chuan Wang","doi":"10.1007/s12026-025-09604-x","DOIUrl":"https://doi.org/10.1007/s12026-025-09604-x","url":null,"abstract":"<p><p>The objective of this study is to determine whether the data of blood profiles before and after therapy can be useful for predicting medium-giant coronary artery aneurysms (CAA) in patients with KD. In total, 1856 KD children from 2013 to 2022 were prospectively recruited. Serial blood samples on the day of initial IVIG infusion and 36-48 h thereafter were collected. The clinical and laboratory parameters were compared between the medium-giant CAA (n = 95) group and the non-CAA group (n = 1761). Multivariate analysis was performed to explore the independent risk factors for medium-giant CAA and the receiver operating characteristic (ROC) curve was used to evaluate and assess the prediction validities. Fever duration prior to initial IVIG infusion, IVIG resistance, cardiac enlargement, white blood cells prior to initial IVIG treatment, albumin levels, and the percentage of △neutrophils were independent risk factors for predicting medium-giant CAA. The predictive value of △neutrophil percentage (≤ 30.2%) demonstrates a relatively high sensitivity (0.84) and a moderate specificity (0.52) for predicting acute medium-giant CAA. The △neutrophil percentage before and 36-48 h after initial IVIG infusion might serve as a promising biomarker in the prediction of medium-giant CAA for KD patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"52"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440834","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}
引用次数: 0
Immunization with recombinant HPV16-E7d in fusion with Flagellin as a cancer vaccine: Effect of antigen-adjuvant orientation on the immune response pattern.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-13 DOI: 10.1007/s12026-025-09598-6
Meysam Gachpazan, Ali Ahmadnia Alashti, Hamid Reza Jahantigh, Majid Moghbeli, Sobhan Faezi, Seyed Younes Hosseini, Mohammad Mahdi Eftekharian, Maryam Nasimi, Farhad Motavalli Khiavi, Alireza Rahimi, Reza Arabi Mianroodi, Mahdi Pakjoo, Morteza Taghizadeh, Maria Tempesta, Mehdi Mahdavi
{"title":"Immunization with recombinant HPV16-E7d in fusion with Flagellin as a cancer vaccine: Effect of antigen-adjuvant orientation on the immune response pattern.","authors":"Meysam Gachpazan, Ali Ahmadnia Alashti, Hamid Reza Jahantigh, Majid Moghbeli, Sobhan Faezi, Seyed Younes Hosseini, Mohammad Mahdi Eftekharian, Maryam Nasimi, Farhad Motavalli Khiavi, Alireza Rahimi, Reza Arabi Mianroodi, Mahdi Pakjoo, Morteza Taghizadeh, Maria Tempesta, Mehdi Mahdavi","doi":"10.1007/s12026-025-09598-6","DOIUrl":"https://doi.org/10.1007/s12026-025-09598-6","url":null,"abstract":"<p><p>Human papillomavirus (HPV) is the leading cause of cervical cancer worldwide. The pathogenesis of HPV is mainly dependent on its E7 and E6 proteins. Up to now, different adjuvants have been used to enhance the efficacy of the immune response against these two proteins. In this study, Flagellin (FLA) was used as adjuvant to test adjuvant activity and also see whether its orientation of attachment can affect the immune response pattern. The E7d-FLA and FLA-E7d in pET28a vector were constructed and then the recombinant proteins were expressed in E. coli BL21 (DE3) bacteria under IPTG induction. The expression of recombinant E7d-FLA and FLA-E7d proteins is confirmed by SDS-PAGE and western blot. Then, recombinant fusion proteins were purified using a nickel-nitrilotriacetic acid (Ni-NTA) column. The recombinant proteins were checked for endotoxin contamination and then quantified by Bradford. Eight-to-ten-week-old male Balb/C mice were immunized subcutaneously with 10 µg recombinant E7d-FLA, FLA-E7d and HPV16E7d vaccine on days 0, 14 and 28. In addition, PBS and FLA groups were considered as control group. Then, spleen cells were harvested to assess lymphocyte proliferation and IFN-γ, IL-4 and IL-17 cytokines. In addition, mice sera were used for specific total IgG and IgG1, IgG2a, IgG2b and IgM antibodies assessment by ELISA. The results show that E7d-FLA is more potent in the induction of lymphocyte proliferation, CTL response and specific total IgG, IgG2a and IgG2b response, while the FLA-E7d vaccine was associated with more IFN-γ, and IL-17 cytokine response. The results of this study proved the ability of FLA as an adjuvant in fusion with E7d in the induction of cellular and humoral immune responses. In addition, it also emphasizes that antigen-adjuvant orientation can affect the immune response strength and polarization against HPV E7d vaccine candidate. HIGHLIGHTS: Flagellin is attached to HPV-16 E7d at the C- or N-terminus to create E7d-FLA and FLA-E7d candidate vaccines. The E7d-FLA vaccine showed a significant increase in lymphocyte proliferation, CTL response and IgG response versus FLA-E7d vaccine. The FLA-E7d vaccine is associated with a significant increase in IFN-γ and IL-17 cytokines response versus E7d-FLA vaccine. It seems that that antigen-adjuvant orientation is an important parameter in the strength and polarization of immune response in HPV E7d vaccine candidate.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"50"},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407374","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}
引用次数: 0
PANoptosis-related genes in the prognosis and immune landscape of hepatocellular carcinoma.
IF 3.3 4区 医学
Immunologic Research Pub Date : 2025-02-13 DOI: 10.1007/s12026-025-09603-y
Xiaowu Wang, Liangchen Qu, Zhikai Wen, Zhixuan Wu, Yuxiang Xue, Xuejia Yang, Ziwei Yuan, Yangyang Guo, Xingcheng Lin
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