Background. Observational studies have suggested an association between inflammatory cytokines and Parkinson’s disease (PD). This Mendelian randomization (MR) was conducted to further assess the causal correlations between inflammatory cytokines and PD. Methods. Genetic instruments associated with inflammatory cytokines were extracted from a large summary genome-wide association studies (GWAS) involving 8,293 European participants. Summary-level statistics for PD were obtained from a large-sample GWAS containing 17 studies that involved European participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted (IVW) method. Results. The IVW method indicated that basic fibroblast growth factor (FGFBasic), interleukin-2 (IL-2), and macrophage migration inhibitory factor (MIF) may be suggestively associated with the risk of PD (OR: 0.71, 95%CI: 0.52–0.96, P = 0.027; OR: 1.18, 95%CI: 1.01–1.38, P = 0.041; and OR: 1.23, 95%CI: 1.04–1.46, P = 0.018). In the reverse direction, monokine induced by interferon gamma (MIG), beta nerve growth factor (bNGF), interleukin-17 (IL-17), and interferon gamma (IFNg) are suggested to be the consequences of PD. Conclusion. Our MR analysis indicated that suggestive associations between circulating levels of FGFBasic, IL-2, and MIF and PD risk. In addition, MIG, bNGF, IL-17, and IFNg are more likely to be involved in the development of downstream PD.
{"title":"Assessing the Causal Relationship between Genetically Determined Inflammatory Cytokines and Parkinson’s Disease Risk: A Bidirectional Two-Sample Mendelian Randomization Study","authors":"Hua Xue, Qian Luo, Jiajia Chen, Wenhui Fan","doi":"10.1155/2024/9069870","DOIUrl":"https://doi.org/10.1155/2024/9069870","url":null,"abstract":"<i>Background</i>. Observational studies have suggested an association between inflammatory cytokines and Parkinson’s disease (PD). This Mendelian randomization (MR) was conducted to further assess the causal correlations between inflammatory cytokines and PD. <i>Methods</i>. Genetic instruments associated with inflammatory cytokines were extracted from a large summary genome-wide association studies (GWAS) involving 8,293 European participants. Summary-level statistics for PD were obtained from a large-sample GWAS containing 17 studies that involved European participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted (IVW) method. <i>Results</i>. The IVW method indicated that basic fibroblast growth factor (FGFBasic), interleukin-2 (IL-2), and macrophage migration inhibitory factor (MIF) may be suggestively associated with the risk of PD (OR: 0.71, 95%CI: 0.52–0.96, <i>P</i> = 0.027; OR: 1.18, 95%CI: 1.01–1.38, <i>P</i> = 0.041; and OR: 1.23, 95%CI: 1.04–1.46, <i>P</i> = 0.018). In the reverse direction, monokine induced by interferon gamma (MIG), beta nerve growth factor (bNGF), interleukin-17 (IL-17), and interferon gamma (IFNg) are suggested to be the consequences of PD. <i>Conclusion</i>. Our MR analysis indicated that suggestive associations between circulating levels of FGFBasic, IL-2, and MIF and PD risk. In addition, MIG, bNGF, IL-17, and IFNg are more likely to be involved in the development of downstream PD.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiple myeloma (MM) is an intractable hematological malignancy caused by abnormalities in plasma cells. Combination therapy using antibodies and natural killer (NK) effectors, which are innate immune cells with safe and potent antitumor activity, is a promising approach for cancer immunotherapy and can enhance antitumor effects. Elotuzumab (Elo) is an immune-stimulatory antibody that targets the signaling lymphocytic activation molecule family 7 (SLAMF7) expressed on the surface of MM and NK cells. We confirmed that Elo strongly promoted NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against SLAMF7-positive MM cells in a CD16-dependent NK cell line, and also activated expanded NK cells derived from peripheral blood mononuclear cells of healthy donors and patients with MM in the present study. However, the antitumor effects and genes involved in the direct promotion of NK cell-mediated activation using Elo in CD16-independent NK cells are not clearly known. In this study, we demonstrated that Elo pretreatment significantly enhanced CD16-independent NK cell-mediated cytotoxicity in both SLAMF7-positive MM.1S and SLAMF7-negative K562, U266, and RPMI 8226 tumor cells. Upon direct simulation of CD16-independent NK cells with Elo, increased levels of CD107a degranulation and IFN-γ secretion were observed along with the upregulation of granzyme B, TNF-α, and IL-1α gene expression. The enhanced NK cell function could also be attributed to the increased expression of the transcription factors T-BET and EOMES. Furthermore, the augmentation of the antitumor effects of CD16-independent NK cells upon pretreatment with Elo enhanced the expression of CRTAM, TNFRSF9, EAT-2, and FOXP3 genes and reduced the expression of HSPA6. Our results suggest that Elo directly promotes the cytotoxic function of CD16-independent NK cells against target cells, which is associated with the upregulation of the expression of several NK cell-enhancing genes.
多发性骨髓瘤（MM）是一种由浆细胞异常引起的难治性血液恶性肿瘤。抗体和自然杀伤（NK）效应器是一种先天性免疫细胞，具有安全、有效的抗肿瘤活性，利用抗体和NK效应器进行联合治疗是一种很有前景的癌症免疫疗法，可以增强抗肿瘤效果。艾洛妥珠单抗（Elo）是一种免疫刺激抗体，靶向表达在 MM 和 NK 细胞表面的信号淋巴细胞活化分子家族 7（SLAMF7）。我们证实，在本研究中，Elo 能在 CD16 依赖性 NK 细胞系中强烈促进 NK 细胞介导的针对 SLAMF7 阳性 MM 细胞的抗体依赖性细胞毒性（ADCC），还能激活来自健康供体和 MM 患者外周血单核细胞的扩增 NK 细胞。然而，在 CD16 依赖性 NK 细胞中使用 Elo 直接促进 NK 细胞介导的活化所涉及的抗肿瘤作用和基因尚不清楚。在本研究中，我们证明了 Elo 预处理可显著增强 SLAMF7 阳性 MM.1S 和 SLAMF7 阴性 K562、U266 和 RPMI 8226 肿瘤细胞中 CD16 非依赖性 NK 细胞介导的细胞毒性。用 Elo 直接模拟 CD16 依赖性 NK 细胞后，观察到 CD107a 脱颗粒和 IFN-γ 分泌水平升高，粒酶 B、TNF-α 和 IL-1α 基因表达上调。NK 细胞功能的增强也可归因于转录因子 T-BET 和 EOMES 表达的增加。此外，经 Elo 预处理后，CD16 非依赖性 NK 细胞的抗肿瘤作用增强，CRTAM、TNFRSF9、EAT-2 和 FOXP3 基因的表达增强，HSPA6 基因的表达降低。我们的研究结果表明，Elo 能直接促进 CD16 非依赖性 NK 细胞对靶细胞的细胞毒作用，这与多个 NK 细胞增强基因的表达上调有关。
{"title":"Elotuzumab Enhances CD16-Independent NK Cell-Mediated Cytotoxicity against Myeloma Cells by Upregulating Several NK Cell-Enhancing Genes","authors":"Yan-Hua Wang, Shotaro Hagiwara, Hiroshi Kazama, Yuki Iizuka, Norina Tanaka, Junji Tanaka","doi":"10.1155/2024/1429879","DOIUrl":"https://doi.org/10.1155/2024/1429879","url":null,"abstract":"Multiple myeloma (MM) is an intractable hematological malignancy caused by abnormalities in plasma cells. Combination therapy using antibodies and natural killer (NK) effectors, which are innate immune cells with safe and potent antitumor activity, is a promising approach for cancer immunotherapy and can enhance antitumor effects. Elotuzumab (Elo) is an immune-stimulatory antibody that targets the signaling lymphocytic activation molecule family 7 (SLAMF7) expressed on the surface of MM and NK cells. We confirmed that Elo strongly promoted NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against SLAMF7-positive MM cells in a CD16-dependent NK cell line, and also activated expanded NK cells derived from peripheral blood mononuclear cells of healthy donors and patients with MM in the present study. However, the antitumor effects and genes involved in the direct promotion of NK cell-mediated activation using Elo in CD16-independent NK cells are not clearly known. In this study, we demonstrated that Elo pretreatment significantly enhanced CD16-independent NK cell-mediated cytotoxicity in both SLAMF7-positive MM.1S and SLAMF7-negative K562, U266, and RPMI 8226 tumor cells. Upon direct simulation of CD16-independent NK cells with Elo, increased levels of CD107a degranulation and IFN-<i>γ</i> secretion were observed along with the upregulation of granzyme B, TNF-<i>α</i>, and IL-1<i>α</i> gene expression. The enhanced NK cell function could also be attributed to the increased expression of the transcription factors T-BET and EOMES. Furthermore, the augmentation of the antitumor effects of CD16-independent NK cells upon pretreatment with Elo enhanced the expression of CRTAM, TNFRSF9, EAT-2, and FOXP3 genes and reduced the expression of HSPA6. Our results suggest that Elo directly promotes the cytotoxic function of CD16-independent NK cells against target cells, which is associated with the upregulation of the expression of several NK cell-enhancing genes.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，以关节滑膜炎为主要特征。不同疾病的铁蛋白沉积特异性不同，RA 中铁蛋白沉积的机制尚不明确。因此，本文深入观察了 RA 患者和动物模型的铁蛋白沉积机制。本文应用RA患者血浆、肿瘤坏死因子-α诱导的人滑膜成纤维细胞和胶原蛋白诱导的关节炎动物模型，初步探究了嗜铁细胞增多症的治疗作用。对于 RA 患者，ELISA 检测了谷胱甘肽（GSH）、GPX4、Nrf2、Keap-1 和铁蛋白的蛋白表达。在细胞实验中，麦拉宁或铁蛋白-1可调节人滑膜成纤维细胞的侵袭、线粒体膜电位、活性氧（ROS）表达、标志蛋白等。在动物实验中，32只Sprague-Dawley雄性大鼠被随机分为4组，在胶原蛋白诱导的RA模型中饲养14天，并服用依拉斯汀或铁-1 35天。结果显示，RA 患者的 GSH、GPX4、Nrf2 和 Keap-1 的表达量较低，而铁蛋白的表达量较高，且这些蛋白的表达量在疾病缓解后有显著变化。此外，铁氧化失活还会降低细胞的增殖和迁移能力、线粒体膜电位和 ROS。我们意外地发现，激活高铁血红蛋白可有效抑制 CIA 动物足部肿胀，减少关节炎评分、骨质破坏和关节滑膜炎，并降低血浆中炎症因子的高表达。人类疾病表现与动物模型病理之间存在非线性关系。对人类或动物的铁蛋白沉积进行调节可能会产生不同的效果。
{"title":"Inhibition of Oxidative Stress-Induced Ferroptosis Can Alleviate Rheumatoid Arthritis in Human","authors":"Yang Liu, Jiang Liang, Zongge Sha, Changfu Yang","doi":"10.1155/2024/9943747","DOIUrl":"https://doi.org/10.1155/2024/9943747","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shanshan Cong, Yao Fu, Xibo Zhao, Qiuyan Guo, Tian Liang, Di Wu, Jing Wang, Guangmei Zhang
Background. Ovarian cancer (OV) is characteristic of high incidence rate and fatality rate in the malignant tumors of female reproductive system. Researches on pathogenesis and therapeutic targets for OV need to be continued. This study mainly analyzed the immune-related pathogenesis and discovered the key immunotherapy targets for OV. Methods. WGCNA was used for excavating hub gene modules and hub genes related to the immunity of OV. Enrichment analysis was aimed to analyze the related pathways of hub gene modules. Biological experiments were used for exploring the effect of hub genes on SKOV3 cells. Results. We identified two hub gene modules related to the immunoscore of OV and found that these genes in the modules were related to the extracellular matrix and viral infections. At the same time, we also discovered six hub genes related to the immunity of OV. Among them, KIF26B and CREB3L1 can affect the proliferation, migration, and invasion of SKOV3 cells by the Wnt/β-catenin pathway. Conclusions. The local infection or inflammation of ovarian may affect the immunity of OV. KIF26B and CREB3L1 are expected to be potential targets for the immunotherapy of OV.
背景。卵巢癌（OV）是女性生殖系统恶性肿瘤中发病率和致死率较高的一种。对卵巢癌发病机制和治疗靶点的研究仍需继续。本研究主要分析与免疫相关的发病机制，并发现 OV 的关键免疫治疗靶点。研究方法利用WGCNA挖掘与OV免疫相关的中枢基因模块和中枢基因。富集分析旨在分析枢纽基因模块的相关通路。利用生物学实验探索中枢基因对 SKOV3 细胞的影响。结果我们发现了两个与 OV 免疫得分相关的中枢基因模块，并发现模块中的这些基因与细胞外基质和病毒感染有关。同时，我们还发现了 6 个与 OV 免疫相关的中枢基因。其中，KIF26B和CREB3L1可通过Wnt/β-catenin通路影响SKOV3细胞的增殖、迁移和侵袭。结论卵巢局部感染或炎症可能会影响卵巢癌的免疫力。KIF26B和CREB3L1有望成为卵巢癌免疫治疗的潜在靶点。
{"title":"KIF26B and CREB3L1 Derived from Immunoscore Could Inhibit the Progression of Ovarian Cancer","authors":"Shanshan Cong, Yao Fu, Xibo Zhao, Qiuyan Guo, Tian Liang, Di Wu, Jing Wang, Guangmei Zhang","doi":"10.1155/2024/4817924","DOIUrl":"https://doi.org/10.1155/2024/4817924","url":null,"abstract":"<i>Background</i>. Ovarian cancer (OV) is characteristic of high incidence rate and fatality rate in the malignant tumors of female reproductive system. Researches on pathogenesis and therapeutic targets for OV need to be continued. This study mainly analyzed the immune-related pathogenesis and discovered the key immunotherapy targets for OV. <i>Methods</i>. WGCNA was used for excavating hub gene modules and hub genes related to the immunity of OV. Enrichment analysis was aimed to analyze the related pathways of hub gene modules. Biological experiments were used for exploring the effect of hub genes on SKOV3 cells. <i>Results</i>. We identified two hub gene modules related to the immunoscore of OV and found that these genes in the modules were related to the extracellular matrix and viral infections. At the same time, we also discovered six hub genes related to the immunity of OV. Among them, KIF26B and CREB3L1 can affect the proliferation, migration, and invasion of SKOV3 cells by the Wnt/<i>β</i>-catenin pathway. <i>Conclusions</i>. The local infection or inflammation of ovarian may affect the immunity of OV. KIF26B and CREB3L1 are expected to be potential targets for the immunotherapy of OV.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"1 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxocariasis is one of the most common zoonotic diseases distributed worldwide. This study aimed to estimate the seroprevalence of anti-<i>Toxocara</i> immunoglobulin G (IgG) antibodies and the associated risk factors among general populations living in urban and rural areas of Abadan and Khorramshahr cities in Khuzestan Province, Southwest Iran. This cross-sectional study was conducted between March and September 2022. There were 363 participants (190 females and 173 males) aged from <20 to ≥60 years old. Anti-<i>Toxocara</i> IgG antibodies in serum samples were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). A structured questionnaire was employed to collect information regarding sociodemographic status and probable risk factors associated with toxocariasis. It was found that the seroprevalence rate in males (15.0%, 95% CI = 10.47–21.11) was higher than in females (10.5%, 95% CI = 6.92–15.70). Moreover, we observed that the seroprevalence was higher in participants at younger ages compared to other age ranges (COR = 2.55, 95% CI = 0.92–7.12, <span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 21.148 11.7782" width="21.148pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"></path></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="24.730183800000002 -8.34882 28.185 11.7782" width="28.185pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,24.78,0)"></path></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"></path></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"></path></g><g transform="matrix(.013,0,0,-0.013,46.466,0)"></path></g></svg>).</span></span> The findings of the univariate analysis revealed that residency in rural areas (<span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 21.148 11.7782" width="21.148pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"></use></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"></path></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="24.730183800000002 -8.34882 28.185 11.7782" width="28.185pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><use xlink:href="#g113-47"></use></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,40.224,0)">
弓形虫病是分布于世界各地的最常见的人畜共患疾病之一。本研究旨在估算伊朗西南部胡齐斯坦省阿巴丹市和霍拉姆沙赫尔市城乡居民中抗弓形虫免疫球蛋白 G (IgG) 抗体的血清流行率及相关风险因素。这项横断面研究于 2022 年 3 月至 9 月间进行。共有 363 名参与者（女性 190 人，男性 173 人），年龄在 20 岁至≥60 岁之间。使用市售的酶联免疫吸附试验（ELISA）检测血清样本中的抗毒原虫 IgG 抗体。采用结构化问卷收集有关社会人口状况和与弓形虫病相关的可能风险因素的信息。结果发现，男性的血清阳性率（15.0%，95% CI = 10.47-21.11）高于女性（10.5%，95% CI = 6.92-15.70）。此外，我们还发现，与其他年龄段相比，年轻参与者的血清阳性率更高（COR = 2.55，95% CI = 0.92-7.12）。单变量分析结果显示，居住在农村地区（）、使用未经净化的水（）、与狗接触（）、与土壤接触（）、食用未经适当清洗的蔬菜（）和饮用未经处理的水（）是与弓形虫病相关的风险因素。应在该省不同地区进一步开展以人类和动物为重点的综合研究。本研究提供的数据有助于卫生决策者考虑采取精确的监测和有效的预防措施，以控制这种人畜共患病在普通人群中的传播。
{"title":"Seroprevalence and Potential Risk Factors of Toxocariasis among General Population in Southwest Iran: Implications on the One Health Approach","authors":"Masoud Foroutan, Aida Vafae Eslahi, Shahrzad Soltani, Naser Kamyari, Ehsan Moradi-Joo, Jean-Francois Magnaval, Milad Badri","doi":"10.1155/2024/4246781","DOIUrl":"https://doi.org/10.1155/2024/4246781","url":null,"abstract":"Toxocariasis is one of the most common zoonotic diseases distributed worldwide. This study aimed to estimate the seroprevalence of anti-<i>Toxocara</i> immunoglobulin G (IgG) antibodies and the associated risk factors among general populations living in urban and rural areas of Abadan and Khorramshahr cities in Khuzestan Province, Southwest Iran. This cross-sectional study was conducted between March and September 2022. There were 363 participants (190 females and 173 males) aged from <20 to ≥60 years old. Anti-<i>Toxocara</i> IgG antibodies in serum samples were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). A structured questionnaire was employed to collect information regarding sociodemographic status and probable risk factors associated with toxocariasis. It was found that the seroprevalence rate in males (15.0%, 95% CI = 10.47–21.11) was higher than in females (10.5%, 95% CI = 6.92–15.70). Moreover, we observed that the seroprevalence was higher in participants at younger ages compared to other age ranges (COR = 2.55, 95% CI = 0.92–7.12, <span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 21.148 11.7782\" width=\"21.148pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,13.517,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"24.730183800000002 -8.34882 28.185 11.7782\" width=\"28.185pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,24.78,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.02,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,33.984,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,40.224,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,46.466,0)\"></path></g></svg>).</span></span> The findings of the univariate analysis revealed that residency in rural areas (<span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 21.148 11.7782\" width=\"21.148pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-113\"></use></g><g transform=\"matrix(.013,0,0,-0.013,13.517,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"24.730183800000002 -8.34882 28.185 11.7782\" width=\"28.185pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,24.78,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,31.02,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,33.984,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,40.224,0)\">","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"17 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodrigo T. Camacho-Pacheco, Jessica Hernández-Pineda, Yesenia Brito-Pérez, Noemi Plazola-Camacho, Irma A. Coronado-Zarco, Gabriela Arreola-Ramírez, Mextli Y. Bermejo-Haro, M. Angel Najera-Hernández, Gabriela González-Pérez, Alma Herrera-Salazar, Andrea Olmos-Ortiz, Diana Soriano-Becerril, Claudia Sandoval-Montes, Ricardo Figueroa-Damian, Sandra Rodríguez-Martínez, Ismael Mancilla-Herrera
Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%–42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.
{"title":"Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors","authors":"Rodrigo T. Camacho-Pacheco, Jessica Hernández-Pineda, Yesenia Brito-Pérez, Noemi Plazola-Camacho, Irma A. Coronado-Zarco, Gabriela Arreola-Ramírez, Mextli Y. Bermejo-Haro, M. Angel Najera-Hernández, Gabriela González-Pérez, Alma Herrera-Salazar, Andrea Olmos-Ortiz, Diana Soriano-Becerril, Claudia Sandoval-Montes, Ricardo Figueroa-Damian, Sandra Rodríguez-Martínez, Ismael Mancilla-Herrera","doi":"10.1155/2024/8815767","DOIUrl":"https://doi.org/10.1155/2024/8815767","url":null,"abstract":"Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%–42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"5 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Demby Sandi, Joshua I. Levy, Kesego Tapela, Mark Zeller, Joshua Afari Yeboah, Daniel Frimpong Saka, Donald S. Grant, Gordon A. Awandare, Peter K. Quashie, Kristian G. Andersen, Lily Paemka
The immunological signatures driving the severity of coronavirus disease 19 (COVID-19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected Ghanaians with mild and severe COVID-19, as well as healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with immune suppression, overexpression of proinflammatory cytokines, including CRNN, IL1A, S100A7, and IL23A, and activation of pathways involved in keratinocyte proliferation. SAMD9L was among the differentially regulated interferon-stimulated genes in our mild and severe disease cohorts, suggesting that it may play a critical role in SARS-CoV-2 pathogenesis. By comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530), an elevated expression of antiviral response-related genes was noted in COVID-19-infected Ghanaians. Overall, the study describes immune signatures driving COVID-19 severity in Ghanaians and identifies immune drivers that could serve as potential prognostic markers for future outbreaks or pandemics. It further provides important preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans, which could be contributing to the differences in disease outcomes. Further studies using larger datasets from different populations will expand on these findings.
{"title":"Upper Airway Epithelial Tissue Transcriptome Analysis Reveals Immune Signatures Associated with COVID-19 Severity in Ghanaians","authors":"John Demby Sandi, Joshua I. Levy, Kesego Tapela, Mark Zeller, Joshua Afari Yeboah, Daniel Frimpong Saka, Donald S. Grant, Gordon A. Awandare, Peter K. Quashie, Kristian G. Andersen, Lily Paemka","doi":"10.1155/2024/6668017","DOIUrl":"https://doi.org/10.1155/2024/6668017","url":null,"abstract":"The immunological signatures driving the severity of coronavirus disease 19 (COVID-19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected Ghanaians with mild and severe COVID-19, as well as healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with immune suppression, overexpression of proinflammatory cytokines, including <i>CRNN</i>, <i>IL1A</i>, <i>S100A7</i>, and <i>IL23A</i>, and activation of pathways involved in keratinocyte proliferation. <i>SAMD9L</i> was among the differentially regulated interferon-stimulated genes in our mild and severe disease cohorts, suggesting that it may play a critical role in SARS-CoV-2 pathogenesis. By comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530), an elevated expression of antiviral response-related genes was noted in COVID-19-infected Ghanaians. Overall, the study describes immune signatures driving COVID-19 severity in Ghanaians and identifies immune drivers that could serve as potential prognostic markers for future outbreaks or pandemics. It further provides important preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans, which could be contributing to the differences in disease outcomes. Further studies using larger datasets from different populations will expand on these findings.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"41 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139765752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María José Romero de Ávila, Susana López-López, Aarón García-Blázquez, Almudena Ruiz-García, María Julia González-Gómez, María Luisa Nueda, Victoriano Baladrón, Ignacio Pérez-Roger, Enric Poch, Begoña Ballester-Lurbe, José Javier García-Ramírez, Eva M. Monsalve, María José M. Díaz-Guerra
Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.
{"title":"RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages","authors":"María José Romero de Ávila, Susana López-López, Aarón García-Blázquez, Almudena Ruiz-García, María Julia González-Gómez, María Luisa Nueda, Victoriano Baladrón, Ignacio Pérez-Roger, Enric Poch, Begoña Ballester-Lurbe, José Javier García-Ramírez, Eva M. Monsalve, María José M. Díaz-Guerra","doi":"10.1155/2024/2264799","DOIUrl":"https://doi.org/10.1155/2024/2264799","url":null,"abstract":"Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-<i>γ</i>. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NF<i>κ</i>B and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as <i>Tnf</i>-<i>α</i>, <i>Irf-1</i>, or <i>Cxcl-10</i>. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"11 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case–control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel–Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 − 0.93, <span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 18.973 11.7782" width="18.973pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"></path></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="22.555183800000002 -8.34882 21.921 11.7782" width="21.921pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.605,0)"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"></path></g></svg>),</span></span> dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, <span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 18.973 11.7782" width="18.973pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"></use></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"></use></g></svg><span></span><span><svg height="11.7782pt" style="vertical-align:-3.42938pt" version="1.1" viewbox="22.555183800000002 -8.34882 28.184 11.7782" width="28.184pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"></use></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"></use></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"></path></g></svg>),</span></span> homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, <span>
{"title":"Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses","authors":"Yuehong Chen, Yali Ye, Huan Liu, Zhongling Luo, Qianwei Li, Qibing Xie","doi":"10.1155/2024/6631033","DOIUrl":"https://doi.org/10.1155/2024/6631033","url":null,"abstract":"This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case–control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel–Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 − 0.93, <span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"></path></g></svg>),</span></span> dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, <span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-113\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 28.184 11.7782\" width=\"28.184pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"></path></g></svg>),</span></span> homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, <span>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"32 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haideh Namdari, Farhad Rezaei, Fatemeh Heidarnejad, Mohammad Yaghoubzad-Maleki, Maryam Karamigolbaghi
Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8+ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-α (TNF-α), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.
肾细胞癌（RCC）占全球癌症相关死亡的大多数。CD70 的过表达与 RCC 晚期有关。因此，本研究旨在利用免疫信息学技术开发一种靶向过表达 CD70 的多位面疫苗。在这项研究中，通过连接辅助 T 淋巴细胞和 CD8+ T 淋巴细胞的特异性 CD70 蛋白表位，构建了硅学多表位疫苗。为了增强免疫原性，在 CD70 表位的 N 端和 C 端连接了细胞穿透肽（CPP）、穿透素（pAntp）序列以及肿瘤坏死因子-α（TNF-α）的整个序列。对这些嵌合疫苗的抗原性、过敏性、肽毒性、群体覆盖率和理化性质进行了计算评估。此外，还对完善的三维结构进行了一系列分析，包括 B 细胞表位结构预测和分子对接。选定的疫苗构建体还接受了分子动力学模拟、免疫反应模拟和硅克隆等多种评估。所有疫苗都包含抗原性、无毒性和非过敏性表位，确保广泛覆盖全球人群。疫苗构建体具有良好的理化特性。受疫苗成分排列的影响，嵌合疫苗与 TNF 受体的结合亲和力保持相对稳定。分子对接和动力学分析预测，CD70-CPP-TNF 与 TNF 受体之间存在稳定的相互作用，显示了潜在的功效。利用 pET28a 质粒完成了疫苗核酸序列的硅学密码子优化和克隆。此外，该疫苗还显示出调节体液和细胞免疫反应的能力。总之，研究结果表明嵌合 CD70-CPP-TNF 疫苗具有治疗 RCC 的潜力。不过，还需要通过体外和体内实验进行验证。该试验已在 NCT04696731 和 NCT04046445 上注册。
{"title":"Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma","authors":"Haideh Namdari, Farhad Rezaei, Fatemeh Heidarnejad, Mohammad Yaghoubzad-Maleki, Maryam Karamigolbaghi","doi":"10.1155/2024/2875635","DOIUrl":"https://doi.org/10.1155/2024/2875635","url":null,"abstract":"Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8<sup>+</sup> T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through <i>in vitro</i> and <i>in vivo</i> experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"25 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139588480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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