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Polymorphic Variants in the Vitamin D Receptor and Clinical Parameters of Rheumatoid Arthritis Patients Undergoing Anti-TNF Treatment. 接受抗肿瘤坏死因子治疗的类风湿关节炎患者维生素 D 受体的多态性变异与临床参数
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-10 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0023
Joanna Wielińska, Katarzyna Górna, Jerzy Świerkot, Bartosz Bugaj, Katarzyna Kolossa, Sławomir Jeka, Katarzyna Bogunia-Kubik

Vitamin D levels have been related to the severity and progression of various autoimmune disorders. In this study, we aimed to investigate the impact of genetic variability in the vitamin D receptor (VDR) gene on disease susceptibility and progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. The study comprises 121 RA patients subjected to anti-TNF therapy genotyped for four VDR polymorphic variants: rs1544410 (BsmI), rs2228570 (FokI), rs731236 (TaqI), and rs7975232 (ApaI). There was no significant association between RA susceptibility and VDR genetic variants. The study results revealed that patients with the rs2228570 CC genotype were characterized by lower vitamin D3 levels (p = 0.028) than those with the T allele. Also, the vitamin D3 levels (p = 0.029) and age at diagnosis (p = 0.017) were significantly lower in rs7975232 A allele carriers compared to CC homozygotes. However, after 6 months of therapy, the A allele seemed to be related to lower disease activity score 28 (DAS28) values (p = 0.030) and more common in patients who achieved remission (p = 0.004) compared to the CC genotype. Concerning other investigated polymorphisms, patients carrying rs1544410 AA and rs731236 CC homozygosity had lower C-reactive protein (CRP) levels before therapy (p = 0.009). In conclusion, VDR rs2228570 and rs7975232 polymorphic variants were found to be related to vitamin D3 levels. Moreover, the genotyping of rs7975232 was also useful in evaluating disease onset and disease activity after 6 months of therapy with TNF inhibitors in RA patients.

维生素 D 水平与各种自身免疫性疾病的严重程度和进展有关。在这项研究中,我们旨在调查维生素 D 受体(VDR)基因的遗传变异对接受肿瘤坏死因子(TNF)抑制剂治疗的类风湿性关节炎(RA)患者的疾病易感性和病情进展的影响。该研究包括121名接受抗肿瘤坏死因子治疗的类风湿性关节炎患者,对四种VDR多态变异进行了基因分型:rs1544410(BsmI)、rs2228570(FokI)、rs731236(TaqI)和rs7975232(ApaI)。RA 易感性与 VDR 基因变异之间没有明显关联。研究结果显示,rs2228570 CC 基因型患者的维生素 D3 水平(p = 0.028)低于 T 等位基因患者。此外,与CC等位基因携带者相比,rs7975232 A等位基因携带者的维生素D3水平(p = 0.029)和诊断年龄(p = 0.017)也明显较低。然而,治疗 6 个月后,与 CC 基因型相比,A 等位基因似乎与较低的疾病活动度评分 28(DAS28)值(p = 0.030)有关,并且在获得缓解的患者中更为常见(p = 0.004)。关于其他研究的多态性,携带 rs1544410 AA 和 rs731236 CC 同源基因的患者在治疗前的 C 反应蛋白(CRP)水平较低(p = 0.009)。总之,研究发现 VDR rs2228570 和 rs7975232 多态变异与维生素 D3 水平有关。此外,rs7975232基因分型还有助于评估RA患者接受TNF抑制剂治疗6个月后的发病情况和疾病活动性。
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引用次数: 0
S-Adenosylmethionine Treatment Diminishes the Proliferation of Castration-Resistant Prostate Cancer Cells by Modulating the Expression of miRNAs. S-腺苷蛋氨酸通过调节 miRNAs 的表达减少阉割耐药前列腺癌细胞的增殖
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0022
Thomas Schmidt

AdoMet (S-adenosylmethionine) inhibits cancer cell proliferation and migration via epigenetic alterations. This study aimed to investigate whether AdoMet may cause alterations in microRNA (miRNA) expression profiles that are important for the initiation and progression of prostate cancer. PC-3 cells were treated with AdoMet before miRNA sequencing. A total of 17 differentially expressed miRNAs were detected. Target gene prediction was performed by means of databases. Results were aligned to transcriptomic data. The bioinformatic analysis revealed upregulation of anticancerogenic genes, downregulation of cancerogenic-related processes and pathways. Knocking down hsa-miR-192-5p in PC-3 cells resulted in downregulation of cancer cell proliferation, thus confirming these results.

AdoMet(S-腺苷蛋氨酸)通过表观遗传学改变抑制癌细胞的增殖和迁移。本研究旨在探讨 AdoMet 是否会导致微RNA(miRNA)表达谱的改变,而微RNA对前列腺癌的发生和发展具有重要作用。在进行 miRNA 测序之前,先用 AdoMet 处理 PC-3 细胞。共检测到 17 个差异表达的 miRNA。通过数据库对目标基因进行了预测。结果与转录组数据进行了比对。生物信息学分析表明,抗癌基因上调,致癌相关过程和通路下调。在 PC-3 细胞中敲除 hsa-miR-192-5p 会导致癌细胞增殖下调,从而证实了上述结果。
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引用次数: 0
Novel Insight into Inflammatory Pathways in Acute Pulmonary Embolism in Humans. 人类急性肺栓塞炎症通路的新视角
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-28 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0021
Anna M Imiela, Tomasz P Mikołajczyk, Piotr Pruszczyk

Accumulating data have shown a pathophysiological association between inflammatory pathways and thrombosis. Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and acute pulmonary embolism (APE), is a significant health burden. It involves not only hemodynamic disturbances due to the emboli occluding the pulmonary arteries, but also platelet activation, endothelial dysfunction, and "firing up" of the inflammatory cascade. In humans, the systemic inflammatory state can also be evaluated using plasma levels of C-reactive protein (CRP) and interleukin (IL)-6, which correlate with venous obstruction, thrombus extension, and clinical VTE complications such as postthrombotic syndrome, recurrent thromboembolism, worse quality of life, and functional impairment. The exaggerated inflammatory state during postthrombotic syndrome aligns with severe alterations in endothelial function, such as activation of intercellular adhesion molecule (ICAM)-1 and E-selectin, as well as vascular proteolysis and fibrinolysis. Moreover, a hypercoagulable state, indicated by higher levels of von Willebrand factor (vWF) and factor VIII, is closely associated with the inflammatory response. We aimed to describe the role of basic inflammatory markers in daily clinical practice as well as the most important cytokines (IL-1β, IL-6, IL-8, tumor necrosis factor-a [TNF-α], growth differentiation factor-15 [GDF-15]). These markers could provide valuable insight into the interplay between thrombosis and inflammation, helping inform better management and treatment strategies.

越来越多的数据表明,炎症途径与血栓形成之间存在病理生理学联系。静脉血栓栓塞症(VTE)包括深静脉血栓形成(DVT)和急性肺栓塞(APE),是一种严重的健康负担。它不仅包括因栓子堵塞肺动脉而引起的血液动力学紊乱,还包括血小板活化、内皮功能障碍和炎症级联反应的 "启动"。在人体中,全身炎症状态也可通过血浆中的 C 反应蛋白(CRP)和白细胞介素(IL)-6 水平来评估,这两种物质与静脉阻塞、血栓扩展以及血栓后综合征、复发性血栓栓塞、生活质量下降和功能障碍等 VTE 临床并发症相关。血栓后综合征期间的炎症状态加剧,导致内皮功能发生严重改变,如激活细胞间粘附分子(ICAM)-1 和 E-选择素,以及血管蛋白溶解和纤维蛋白溶解。此外,冯-威廉因子(von Willebrand factor,vWF)和因子 VIII 水平升高所显示的高凝状态与炎症反应密切相关。我们旨在描述基本炎症指标在日常临床实践中的作用以及最重要的细胞因子(IL-1β、IL-6、IL-8、肿瘤坏死因子-a [TNF-α]、生长分化因子-15 [GDF-15])。这些标志物可为了解血栓形成与炎症之间的相互作用提供宝贵的信息,有助于制定更好的管理和治疗策略。
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引用次数: 0
S-Adenosylmethionine Inhibits the Proliferation of Retinoblastoma Cell Y79, Induces Apoptosis and Cell Cycle Arrest of Y79 Cells by Inhibiting the Wnt2/β-Catenin Pathway. S-腺苷蛋氨酸通过抑制 Wnt2/β-Catenin 通路抑制视网膜母细胞瘤细胞 Y79 的增殖,诱导 Y79 细胞凋亡和细胞周期停滞。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-04 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0020
Mushi Liu, Youchaou Mobet, Hong Shen

Retinoblastoma is one of the most common primary intraocular malignancies in young children. Traditional treatment methods such as chemotherapy often come with significant adverse effects, such as hearing loss, cognitive impairment, and vision loss. Therefore, there is an urgent need to explore a novel therapeutic drug that is both effective and safe. S-adenosylmethionine (SAM) is a natural compound known to exhibit anti-proliferative effects in various cancer cell lines. However, to date, no studies investigated the effects of SAM on retinoblastoma cells and its potential mechanisms of action. Therefore, this study aims to investigate the impact of SAM on retinoblastoma cells and explore its possible mechanisms of action, with the hope of providing new insights into the treatment of this disease. The optimal concentration of SAM was determined using the Cell Counting Kit-8 assay. The effect of SAM on retinoblastoma proliferation was assessed using the 5-ethynyl-2'-deoxyuridine cell proliferation assay. Y79 cells were subjected to hematoxylin and eosin stain and electron microscopy to observe any morphological changes induced by SAM. The stages of SAM's action on the retinoblastoma cell cycle and its apoptotic effects were measured using flow cytometry. The apoptotic effect of SAM on retinoblastoma was further confirmed using the TUNEL assay. Differential expression of related genes was detected through RT-PCR. In vivo subcutaneous tumor formation in nude mice and immunohistochemistry were employed to validate the effect of SAM on retinoblastoma-related phenotypes. Western blotting was conducted to investigate whether SAM modulated retinoblastoma-related phenotypes via the Wnt2/β-catenin pathway. SAM arrested the cell cycle of retinoblastoma at the G1 phase, induced apoptosis of retinoblastoma cells through the Wnt2/β-catenin pathway, and affected their morphology and even ultrastructure. In addition, in vitro and in vivo experiments demonstrated that SAM had an oncogenic effect on retinoblastoma. In this study, we verify in vitro and in vivo whether SAM inhibits the proliferation of retinoblastoma cell Y7, induces apoptosis and cell cycle arrest of Y79 cells by inhibiting the Wnt2/β-catenin pathway, and affects the morphology and structure of retinoblastoma cell Y79.

视网膜母细胞瘤是幼儿最常见的原发性眼内恶性肿瘤之一。化疗等传统治疗方法往往会带来严重的不良反应,如听力下降、认知障碍和视力减退。因此,迫切需要探索一种既有效又安全的新型治疗药物。众所周知,S-腺苷蛋氨酸(SAM)是一种天然化合物,在多种癌细胞系中具有抗增殖作用。然而,迄今为止,还没有研究调查过 SAM 对视网膜母细胞瘤细胞的影响及其潜在的作用机制。因此,本研究旨在调查亚麻酸对视网膜母细胞瘤细胞的影响,并探索其可能的作用机制,希望能为这种疾病的治疗提供新的见解。研究采用细胞计数试剂盒-8测定法确定了SAM的最佳浓度。使用 5-乙炔基-2'-脱氧尿苷细胞增殖试验评估了 SAM 对视网膜母细胞瘤增殖的影响。对 Y79 细胞进行苏木精和伊红染色,并用电子显微镜观察 SAM 诱导的任何形态变化。使用流式细胞术测量了 SAM 对视网膜母细胞瘤细胞周期的作用阶段及其凋亡效应。TUNEL 试验进一步证实了 SAM 对视网膜母细胞瘤的凋亡作用。通过 RT-PCR 检测了相关基因的差异表达。采用裸鼠体内皮下肿瘤形成和免疫组织化学方法验证了 SAM 对视网膜母细胞瘤相关表型的影响。通过 Western 印迹法研究 SAM 是否通过 Wnt2/β-catenin 通路调节视网膜母细胞瘤相关表型。结果表明,SAM能将视网膜母细胞瘤的细胞周期阻滞在G1期,通过Wnt2/β-catenin途径诱导视网膜母细胞瘤细胞凋亡,并影响其形态甚至超微结构。此外,体外和体内实验证明,SAM 对视网膜母细胞瘤有致癌作用。本研究在体外和体内验证了SAM是否能抑制视网膜母细胞瘤细胞Y7的增殖,通过抑制Wnt2/β-catenin通路诱导Y79细胞凋亡和细胞周期停滞,并影响视网膜母细胞瘤细胞Y79的形态和结构。
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引用次数: 0
Endothelial Activation and Stress Index Score as a Prognostic Factor of Cytokine Release Syndrome in CAR-T Patients - A Retrospective Analysis of Multiple Myeloma and Large B-Cell Lymphoma Cohorts. 作为 CAR-T 患者细胞因子释放综合征预后因素的内皮活化和压力指数评分--对多发性骨髓瘤和大 B 细胞淋巴瘤队列的回顾性分析。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-14 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0018
Jaromir Tomasik, Batia Avni, Sigal Grisariu, Shlomo Elias, Eran Zimran, Polina Stepensky, Grzegorz W Basak

Endothelial Activation and Stress Index (EASIX) has been proposed as a prognostic factor of adverse events or survival in hematological malignancies. Endothelial dysfunction has been associated with complications following stem cell transplantation and chimeric antigen receptor (CAR)-T therapy. This retrospective cohort study evaluated the utility of the EASIX score as a prognostic factor of cytokine release syndrome (CRS) in multiple myeloma/light-chain amyloidosis (MM/AL amyloidosis; N = 69) and large B-cell lymphoma (LBCL) cohorts (N = 65). Occurrence of CRS grade ≥3 was the primary endpoint. For both cohorts, the EASIX and simplified EASIX (s-EASIX) scores were calculated at four different time points before CAR-T infusion to assess its prognostic value. In the MM/AL amyloidosis cohort, neither EASIX nor s-EASIX scores calculated at any time point were associated with the occurrence of CRS grade ≥3. In the LBCL cohort, EASIX and s-EASIX scores measured before lymphodepletion (EASIX-pre and s-EASIX-pre) showed a significant relationship with CRS grade ≥3 (odds ratio [OR] = 1.06 and OR = 1.05, respectively). The cutoff value of 1.835 for EASIX-pre was associated with 4.59-fold increased OR of CRS grade ≥3 (95% confidence interval [CI]: 1.13-21.84), whereas s-EASIX-pre cutoff equaled 2.134 and was associated with 4.13-fold increased OR of CRS grade ≥3 (95% CI: 1.01-17.93). However, after internal validation with bootstrapping, the significance was lost both for the EASIX-pre and s-EASIX-pre cutoff. The presented findings indicate that the EASIX scores fail to predict CRS in MM/amyloidosis CAR-T patients, whereas they can be implemented as CRS grade ≥3 predictors in LBCL CAR-T patients.

内皮活化和应激指数(EASIX)被认为是血液恶性肿瘤不良事件或存活率的预后因素。内皮功能障碍与干细胞移植和嵌合抗原受体(CAR)-T疗法后的并发症有关。这项回顾性队列研究评估了EASIX评分作为多发性骨髓瘤/轻链淀粉样变性(MM/AL amyloidosis;N = 69)和大B细胞淋巴瘤(LBCL)队列(N = 65)中细胞因子释放综合征(CRS)预后因素的实用性。CRS≥3级的发生率是主要终点。对于这两个队列,在CAR-T输注前的四个不同时间点计算EASIX和简化EASIX(s-EASIX)评分,以评估其预后价值。在 MM/AL 淀粉样变性队列中,在任何时间点计算的 EASIX 和 s-EASIX 分数都与 CRS ≥3 级的发生无关。在LBCL队列中,淋巴清除前测定的EASIX和s-EASIX评分(EASIX-pre和s-EASIX-pre)与CRS≥3级有显著关系(几率比[OR]分别为1.06和1.05)。EASIX-pre 临界值为 1.835 时,CRS 分级≥3 的 OR 增加了 4.59 倍(95% 置信区间 [CI]:1.13-21.84),而 s-EASIX-pre 临界值为 2.134 时,CRS 分级≥3 的 OR 增加了 4.13 倍(95% 置信区间 [CI]:1.01-17.93)。然而,经过引导法内部验证后,EASIX-pre 和 s-EASIX-pre 临界值的显著性均已丧失。本文的研究结果表明,EASIX评分无法预测MM/淀粉样变性CAR-T患者的CRS,而它们可以作为LBCL CAR-T患者CRS等级≥3的预测指标。
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引用次数: 0
Apoptosis Regulation in Dental Pulp Cells and PD-1/PD-L1 Expression Dynamics Under Ozone Exposure - A Pilot Approach. 臭氧暴露下牙髓细胞的凋亡调控和 PD-1/PD-L1 表达动态--一种试点方法。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-14 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0019
Maja Ptasiewicz, Mirosław Orłowski, Agnieszka Magryś, Janusz Kocki, Krzysztof Gosik, Piotr Stachurski, Renata Chałas

This study aimed to determine the effect of ozone on the expression of Bax and Bcl-2 genes in dental pulp cells. Additionally, the programmed cell death protein 1, programmed death-ligand 1, and CD200 antigens were determined in lymphocytes to assess their surface expression. Dental pulp cells were cultured from extracted healthy third molars and characterized as dental pulp stromal cells. Gene expression of Bcl-2 and Bax was analyzed at 0 s, 6 s, and 12 s of ozone exposure using real-time PCR. Lymphocytes from dental pulp were subjected to ozone exposure for 12 s and PD-1, PD-L1, and CD200/CD200R expression was analyzed by flow cytometry. Upon exposure to ozone for 6 s, the Bcl-2 expression decreased significantly to -0.09, and at 12 s, it increased significantly to 0.3. Bax gene expression level increased significantly to 0.188 after 6 s exposure, and at 12 s, to 0.16. Lymphocytes exposed to ozone for 12 s showed minimal changes in PD-1, PD-L1, and CD200/CD200R expression levels, indicating that oxidative stress does not impact the signaling pathways regulating these molecules. The significant upregulation of Bcl-2 at 12 s highlights the cells' effort to protect themselves from prolonged oxidative stress, possibly tipping the balance toward cell survival and tissue repair. However, the absence of changes in PD-1 and PD-L1 expression on lymphocytes under oxidative stress suggests that these molecules are not sensitive to oxidative stress in this context.

本研究旨在确定臭氧对牙髓细胞中 Bax 和 Bcl-2 基因表达的影响。此外,还测定了淋巴细胞中的程序性细胞死亡蛋白1、程序性死亡配体1和CD200抗原,以评估它们的表面表达。从拔出的健康第三磨牙中培养牙髓细胞,并将其鉴定为牙髓基质细胞。使用实时 PCR 分析了臭氧暴露 0 秒、6 秒和 12 秒时 Bcl-2 和 Bax 的基因表达。将牙髓中的淋巴细胞置于臭氧中 12 秒钟,然后用流式细胞术分析 PD-1、PD-L1 和 CD200/CD200R 的表达。接触臭氧 6 秒钟后,Bcl-2 的表达明显降低至-0.09,12 秒钟后则明显升高至 0.3。Bax 基因的表达水平在暴露于臭氧 6 秒后明显升高至 0.188,12 秒后升高至 0.16。淋巴细胞暴露于臭氧 12 秒后,PD-1、PD-L1 和 CD200/CD200R 的表达水平变化极小,这表明氧化应激不会影响调节这些分子的信号通路。12 秒钟后 Bcl-2 的表达明显上调,这表明细胞在长时间的氧化应激中努力保护自己,从而可能使细胞存活和组织修复的天平发生倾斜。然而,在氧化应激下淋巴细胞上的 PD-1 和 PD-L1 表达没有变化,这表明在这种情况下这些分子对氧化应激并不敏感。
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引用次数: 0
Angiotensin II Type 2 Receptor Antibodies in Glomerular Diseases. 肾小球疾病中的血管紧张素 II 2 型受体抗体
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0017
Maciej Szymczak, Harald Heidecke, Marcelina Żabińska, Dagna Rukasz, Krzysztof Wiśnicki, Krzysztof Kujawa, Katarzyna Kościelska-Kasprzak, Magdalena Krajewska, Mirosław Banasik

We evaluated the concentration of AT2R antibodies in 136 patients with primary and secondary glomerular diseases: membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (n = 25), systemic lupus erythematosus (n = 17), immunoglobulin A (IgA) nephropathy (n = 14), mesangial (non-IgA) proliferative nephropathy (n = 6), c-ANCA vasculitis (n = 40), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and compared it with a healthy control group (22 patients). Serum creatinine levels, proteinuria, serum albumin, and total protein concentrations were prospectively recorded for 2 years. The mean levels of AT2R antibodies in the lupus nephropathy group were significantly higher compared to the control group, 64.12 ± 26.95 units/mL and 9.72 ± 11.88 units/mL, respectively. There was no association between this level and the clinical course of the disease. The AT2R levels in other kinds of glomerular disease were no different from the control group. We found significant correlations between AT1R and AT2R in patients with membranous nephropathy (r = 0.66), IgA nephropathy (r = 0.61), and c-ANCA vasculitis (r = 0.63). Levels of AT2R antibodies in systemic lupus erythematosus are higher compared to other types of glomerulonephritis, vasculitis, and a healthy control group. Levels of AT2R antibodies correlate with AT1R antibodies in the groups of patients with membranous nephropathy, IgA nephropathy, and c-ANCA vasculitis. These kinds of AT2R antibodies have a stimulative effect on AT2R, but we have not found the influence of these antibodies on the clinical course of glomerular diseases.

我们对 136 名原发性和继发性肾小球疾病患者的 AT2R 抗体浓度进行了评估:膜性肾病(18 例)、局灶性和节段性肾小球硬化(25 例)、系统性红斑狼疮(17 例)、免疫球蛋白 A(IgA)肾病(14 例)、间质(非 IgA)增生性肾病(6 例)、c-ANCA 血管炎(40 例)、核周抗中性粒细胞胞浆抗体(p-ANCA)血管炎(16 例),并与健康对照组(22 例)进行比较。对血清肌酐水平、蛋白尿、血清白蛋白和总蛋白浓度进行了为期两年的前瞻性记录。狼疮肾病组的 AT2R 抗体平均水平明显高于对照组,分别为 64.12 ± 26.95 单位/毫升和 9.72 ± 11.88 单位/毫升。该水平与疾病的临床过程没有关联。其他类型肾小球疾病患者的 AT2R 水平与对照组无差异。我们发现膜性肾病(r = 0.66)、IgA 肾病(r = 0.61)和 c-ANCA 血管炎(r = 0.63)患者的 AT1R 和 AT2R 之间存在明显相关性。与其他类型的肾小球肾炎、血管炎和健康对照组相比,系统性红斑狼疮患者的 AT2R 抗体水平较高。在膜性肾病、IgA 肾病和 c-ANCA 血管炎患者中,AT2R 抗体的水平与 AT1R 抗体相关。这些AT2R抗体对AT2R有刺激作用,但我们尚未发现这些抗体对肾小球疾病的临床过程有影响。
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引用次数: 0
The Healthcare Study Examines the Humoral Anti-S1 Antibody Response Following mRNA Vaccination, Comparing Individuals with and without Prior SARS-CoV-2 Infection. 医疗保健研究对接种 mRNA 疫苗后的体液抗 S1 抗体反应进行了研究,并对之前感染过 SARS-CoV-2 和未感染过 SARS-CoV-2 的患者进行了比较。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0016
Małgorzata Staruszkiewicz, Anna Pituch-Noworolska, Mohamad Skayne, Torsten Matthias, Szymon Skoczen

Vaccines targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been pivotal in curtailing the spread of infection. Health care workers, as frontline responders, were among the first to receive vaccination to mitigate coronavirus disease in 2019 (COVID-19) transmission. This study aimed to assess the humoral response elicited by mRNA vaccines, specifically measuring antibodies against the spike S1 protein, a marker of immune response. A cohort of 649 health care workers received three doses of mRNA vaccine, with antibody levels evaluated before and after each dose within a 2- to 3-week interval. Participants were stratified into groups based on prior exposure to the virus: those without prior contact (440 individuals) and those with a history of infection (209 individuals). Among the latter, cases of SARS-CoV-2 infection ranged from asymptomatic (92 individuals) to mild symptomatic (117 individuals). Participants with a history of infection exhibited elevated levels of IgG antibodies against the S1 protein prior to vaccination. Notably, both immunoglobulin IgA class (IgA) and immunoglobulin IgG class (IgG) antibody responses increased significantly post-vaccination, peaking after the second dose for IgG and after the third dose for IgA. Interestingly, the immune response to the vaccine did not vary significantly based on the symptomatic or asymptomatic nature of prior infection. Furthermore, the study findings indicate that completion of the vaccination regimen led to sustained antibody production lasting between 6 months and 9 months. This study underscores the robust and enduring humoral response elicited by mRNA vaccines, particularly among health care workers, irrespective of prior SARS-CoV-2 exposure.

针对严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)的疫苗在遏制感染传播方面发挥了关键作用。医护人员作为一线响应者,是首批接种疫苗以缓解 2019 年冠状病毒病(COVID-19)传播的人员之一。本研究旨在评估 mRNA 疫苗引起的体液反应,特别是测量针对免疫反应标志物尖峰 S1 蛋白的抗体。649 名医护人员共接种了三剂 mRNA 疫苗,每剂疫苗接种前后间隔 2-3 周对抗体水平进行评估。根据之前接触病毒的情况将参与者分为两组:未曾接触过病毒者(440 人)和有感染史者(209 人)。在后者中,SARS-CoV-2 感染病例从无症状(92 人)到轻微症状(117 人)不等。在接种疫苗前,有感染史的参与者体内针对 S1 蛋白的 IgG 抗体水平升高。值得注意的是,免疫球蛋白 IgA 类(IgA)和免疫球蛋白 IgG 类(IgG)抗体反应在接种疫苗后都显著增加,IgG 在第二剂后达到高峰,IgA 在第三剂后达到高峰。有趣的是,疫苗免疫反应并不因先前感染的无症状或无症状性质而有明显差异。此外,研究结果表明,完成疫苗接种后,抗体的产生可持续 6 个月到 9 个月。这项研究强调了 mRNA 疫苗所引起的强大而持久的体液反应,尤其是在医护人员中,与之前是否感染过 SARS-CoV-2 无关。
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引用次数: 0
Clinical Significance of IgG4 Serum Concentration in Graves' Disease. 巴塞杜氏病 IgG4 血清浓度的临床意义
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-07-20 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0015
Michal Olejarz, Ewelina Szczepanek-Parulska, Aleksandra Krygier, Elzbieta Wrotkowska, Nadia Sawicka-Gutaj, Marek Ruchala

Elevated immunoglobulin G4 (IgG4) serum antibodies are an important feature of IgG4-related disease. However, IgG4 antibodies can play a role in autoimmune thyroid disorders. In this study, we aimed to evaluate the impact of serum IgG4 levels on clinical features of Graves' disease (GD). We recruited 60 patients with GD (48 patients without thyroid eye disease, 12 patients with moderate-to-severe Graves' orbitopathy [GO], and 25 healthy control subjects). The prevalence of high IgG4 serum concentration was 4.2% among GD patients without GO and 33.33% in patients with moderate-to-severe GO. The group with GO had significantly higher median IgG4 levels (87.9 mg/dL) than the control group (41.2 mg/dL, P = 0.034) and the GD without GO group (30.75 mg/dL, P < 0.001). Patients with thyroid nodules had lower IgG4 levels than patients without thyroid nodules, but the difference was not statistically significant (35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL, P = 0.064). IgG4 as a diagnostic tool for moderate-to-severe GO had the following parameters: area under the curve (AUC): 0.851 (P < 0.001), at the cut-off value of 49 mg/dL, negative predictive value: 100%, positive predictive value: 48%, sensitivity: 100%, specificity: 73%. There were no significant differences between the high and normal IgG4 groups in thyroid hormones, antithyroid antibodies, and ultrasound features. Serum IgG4 levels are associated with some of the clinical features of GD and can help in the diagnostic process of the disease. More research is needed to better understand the pathophysiology of IgG4 involvement in GD.

免疫球蛋白 G4(IgG4)血清抗体升高是 IgG4 相关疾病的一个重要特征。然而,IgG4抗体也可能在自身免疫性甲状腺疾病中发挥作用。在这项研究中,我们旨在评估血清 IgG4 水平对巴塞杜氏病(GD)临床特征的影响。我们招募了 60 名 GD 患者(48 名无甲状腺眼病患者、12 名中重度巴塞杜氏眶病 [GO] 患者和 25 名健康对照组受试者)。在未患有巴塞杜氏眼病的 GD 患者中,IgG4 血清高浓度的发生率为 4.2%,而在中重度巴塞杜氏眼病患者中,IgG4 血清高浓度的发生率为 33.33%。GO组的IgG4水平中位数(87.9 mg/dL)明显高于对照组(41.2 mg/dL,P = 0.034)和无GO的GD组(30.75 mg/dL,P < 0.001)。甲状腺结节患者的 IgG4 水平低于无甲状腺结节患者,但差异无统计学意义(35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL,P = 0.064)。作为中度至重度 GO 的诊断工具,IgG4 的参数如下:曲线下面积(AUC)为 0.851(P < 0.05):0.851 (P < 0.001),临界值为 49 mg/dL;阴性预测值:100%;阳性预测值:48%;灵敏度:100%;特异性:100%:灵敏度:100%,特异性:73%。高 IgG4 组和正常 IgG4 组在甲状腺激素、抗甲状腺抗体和超声特征方面无明显差异。血清 IgG4 水平与 GD 的某些临床特征相关,有助于疾病的诊断过程。要更好地了解 IgG4 参与 GD 的病理生理学,还需要进行更多的研究。
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引用次数: 0
Solute Carrier Transporters in Synovial Membrane and Hoffa's Pad of Patients with Rheumatoid Arthritis. 类风湿性关节炎患者滑膜和霍法垫中的溶质载体转运体
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-06-27 eCollection Date: 2024-01-01 DOI: 10.2478/aite-2024-0014
Damian Malinowski, Katarzyna Piotrowska, Marek Droździk, Andrzej Pawlik

Rheumatoid arthritis (RA) is a complex autoimmune disease that leads to joint destruction. A number of immune cells that affect joint tissues are involved in the pathogenesis of this disease. This leads to the synthesis of many pro-inflammatory mediators. The transport of drugs, as well as many cytokines involved in the development of inflammation in RA patients, is mediated by membrane transporters. Membrane transporters are proteins that mediate the transfer of substrates across biological membranes. But to date there are no studies examining the expression of solute carrier (SLC) transporters in joint tissues. The aim of the study was to evaluate the expression of individual SLC family transporters in the synovial membranes (SMs) and infrapatellar fat pad (Hoffa's pad) of RA patients. The study included 20 patients with rheumatoid arthritis and 20 with osteoarthritis as the control group who were undergoing joint replacement surgery as a normal part of clinical care. In the SM and Hoffa's pad of RA patients the following 17 membrane transporters were defined at relevant expression levels for SLC transporter superfamily: SLC15A2, SLC16A3, SLC19A1, SLC2A9, SLC22A1, SLC22A3, SLC22A4, SLC22A5, SLC22A18, SLC33A1, SLC47A1, SLC51A, SLC7A5, SLC7A6, SLC01C1, SLC02B1, SLC04A1. The confirmed expression of these transporters in the SMs as well as Hoffa's pad of patients with RA and OA, and the differences in their expression between these groups, suggests the involvement of SLC transporters in both the maintenance of homeostasis under physiological conditions in the tissues of the joints, as well as in the inflammatory process in RA.

类风湿性关节炎(RA)是一种复杂的自身免疫性疾病,会导致关节破坏。许多影响关节组织的免疫细胞参与了这种疾病的发病机制。这导致许多促炎介质的合成。药物的转运以及与 RA 患者炎症发展有关的许多细胞因子都是由膜转运体介导的。膜转运体是介导底物跨生物膜转移的蛋白质。但迄今为止,还没有研究检测关节组织中溶质载体(SLC)转运体的表达。该研究旨在评估SLC家族转运体在RA患者滑膜(SMs)和髌下脂肪垫(Hoffa's pad)中的表达情况。研究对象包括20名类风湿性关节炎患者和20名骨关节炎患者,作为对照组,这些患者接受关节置换手术,这是临床治疗的正常部分。在类风湿性关节炎患者的 SM 和霍法垫中,确定了以下 17 种膜转运体在 SLC 转运体超家族中的相关表达水平:SLC15a2、SLC16a3、SLC19a1、SLC2a9、SLC22a1、SLC22a3、SLC22a4、SLC22a5、SLC22a18、SLC33a1、SLC47a1、SLC51a、SLC7a5、SLC7a6、SLC01c1、SLC02b1、SLC04a1。SLC转运体在RA和OA患者的SM和Hoffa's垫中的表达得到证实,而且这些转运体在这两组患者中的表达存在差异,这表明SLC转运体既参与了关节组织在生理条件下维持平衡的过程,也参与了RA的炎症过程。
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Archivum Immunologiae et Therapiae Experimentalis
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