BMC Immunology最新文献_第6页

A novel chimeric vaccine containing multiple epitopes for simulating robust immune activation against Klebsiella pneumoniae 一种含有多个表位的新型嵌合疫苗，可模拟针对肺炎克雷伯菌的强效免疫激活

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-05-05 DOI: 10.1186/s12865-024-00617-z

Morteza Hakimian, Abbas Doosti, Ali Sharifzadeh

Due to antibiotic resistance, the Klebsiella genus is linked to morbidity and death, necessitating the development of a universally protective vaccine against Klebsiella pathogens. Core sequence analysis prioritized non-redundant host molecules and expected lipid bilayer peptides from fully sequenced Klebsiella genomes. These proteins were refined to identify epitopes, examining their immunogenicity, toxicity, solubility, and interaction with MHC alleles. Epitopes were linked to CPG ODN C274 via EAAAK, HEYGAEALERAG, and GGGS linkers to enhance immunological responses. The vaccine’s tertiary structure was modelled and docked with MHC-I and MHC-II. Fifty-five proteins were recognized in the Vaxign collection as having remarkable features. Twenty-three proteins with potential pathogenicity were then identified. Eight options for vaccines emerged after the immunogenicity of proteins was examined. The best antigens were three proteins: MrkD, Iron-regulated lipid membrane polypeptides, and RmpA. These compounds were selected for their sensitivity. The structural protein sequences of K. pneumoniae were utilized to identify seven CTL epitopes, seven HTL epitopes, and seven LBL epitopes, respectively. The produced immunization displayed a stable contact with the receptors, based on molecular dynamic simulations lasting 250 nanoseconds. Intermolecular binding free energies also indicated the dominance of the van der Waals and electrostatic energies. In summary, the results of this study might help scientists develop a novel vaccine to prevent K. pneumoniae infections.

由于抗生素耐药性，克雷伯氏菌属与发病和死亡有关，因此有必要开发一种针对克雷伯氏菌病原体的通用保护性疫苗。核心序列分析从完全测序的克雷伯氏菌基因组中优先选择了非冗余宿主分子和预期脂双层肽。对这些蛋白质进行了提炼，以确定表位，检查其免疫原性、毒性、可溶性以及与 MHC 等位基因的相互作用。表位通过 EAAAK、HEYGAEALERAG 和 GGGS 连接器与 CPG ODN C274 连接，以增强免疫反应。对疫苗的三级结构进行了建模，并与 MHC-I 和 MHC-II 进行了对接。Vaxign 收集的 55 种蛋白质被认为具有显著特征。随后又确定了 23 种具有潜在致病性的蛋白质。在对蛋白质的免疫原性进行检查后，出现了八种疫苗选择。最佳抗原是三种蛋白质：MrkD、铁调节脂膜多肽和 RmpA。这些化合物因其敏感性而被选中。利用肺炎双球菌的结构蛋白序列，分别确定了七个 CTL 表位、七个 HTL 表位和七个 LBL 表位。根据持续 250 纳秒的分子动力学模拟，所产生的免疫与受体有稳定的接触。分子间结合自由能也表明范德华能和静电能占主导地位。总之，这项研究的结果可能有助于科学家们开发出一种新型疫苗来预防肺炎双球菌感染。

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引用次数: 0

Atypical memory B cells increase in the peripheral blood of patients with breast cancer regardless of lymph node involvement 乳腺癌患者外周血中的非典型记忆 B 细胞增多，与淋巴结受累无关

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-05-03 DOI: 10.1186/s12865-024-00620-4

Atefeh Azizi, Fereshteh Mehdipour, Morteza Samadi, Reza Rasolmali, Abdol-Rasoul Talei, Abbas Ghaderi

Breast cancer is the most common cancer in females. The immune system has a crucial role in the fight against cancer. B and T cells, the two main components of the adaptive immunity, are critical players that specifically target tumor cells. However, B cells, in contrast to T cells, and their role in cancer inhibition or progression is less investigated. Accordingly, in this study, we assessed and compared the frequency of naïve and different subsets of memory B cells in the peripheral blood of patients with breast cancer and healthy women. We found no significant differences in the frequencies of peripheral CD19+ B cells between the patients and controls. However, there was a significant decrease in the frequency of CD19+IgM+ B cells in patients compared to the control group (P=0.030). Moreover, the patients exhibited higher percentages of atypical memory B cells (CD19+CD27‒IgM‒, P=0.006) and a non-significant increasing trend in switched memory B cells (CD19+CD27+IgM‒, P=0.074). Further analysis revealed a higher frequency of atypical memory B cells (aMBCs) in the peripheral blood of patients without lymph node involvement as well as those with a tumor size greater than 2cm or with estrogen receptor (ER) negative/progesterone receptor (PR) negative tumors, compared with controls (P=0.030, P=0.040, P=0.031 and P=0.054, respectively). Atypical memory B cells (CD19+CD27‒IgM‒) showed a significant increase in the peripheral blood of patients with breast cancer compared to the control group. This increase seems to be associated with tumor characteristics. Nevertheless, additional research is necessary to determine the precise role of these cells during breast cancer progression

乳腺癌是女性最常见的癌症。免疫系统在抗癌过程中起着至关重要的作用。B 细胞和 T 细胞是适应性免疫的两个主要组成部分，它们是专门针对肿瘤细胞的关键角色。然而，与 T 细胞相比，B 细胞及其在癌症抑制或进展中的作用却鲜有研究。因此，在这项研究中，我们评估并比较了乳腺癌患者和健康女性外周血中原始 B 细胞和不同亚群记忆 B 细胞的频率。我们发现，患者和对照组外周 CD19+ B 细胞的频率没有明显差异。然而，与对照组相比，患者体内 CD19+IgM+ B 细胞的频率明显下降（P=0.030）。此外，患者的非典型记忆 B 细胞（CD19+CD27-IgM-，P=0.006）比例较高，而转换记忆 B 细胞（CD19+CD27+IgM-，P=0.074）的增加趋势不明显。进一步分析发现，与对照组相比，无淋巴结受累、肿瘤大小超过2厘米或雌激素受体（ER）阴性/孕激素受体（PR）阴性的患者外周血中非典型记忆B细胞（aMBCs）的频率更高（分别为P=0.030、P=0.040、P=0.031和P=0.054）。与对照组相比，乳腺癌患者外周血中的非典型记忆 B 细胞（CD19+CD27-IgM-）显著增加。这种增加似乎与肿瘤特征有关。然而，要确定这些细胞在乳腺癌进展过程中的确切作用，还需要进行更多的研究。

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引用次数: 0

The role of the immune system in early-onset schizophrenia: identifying immune characteristic genes and cells from peripheral blood 免疫系统在早发型精神分裂症中的作用：从外周血中识别免疫特征基因和细胞

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-05-03 DOI: 10.1186/s12865-024-00618-y

Zi Chen, Yuxue Li, Yao Gao, Xiaoxuan Fan, Xinzhe Du, Xinrong Li, Zhifen Liu, Sha Liu, Xiaohua Cao

Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology. We obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm. We selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7. Our results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.

早发型精神分裂症（EOS）是精神分裂症（SCZ）的一种类型，发病年龄为 0.7 岁。我们的研究结果表明，SCZ 患者的免疫系统功能发生了改变。此外，CCL8、PSMD1、AVPR1B 和 SEMG1 可调控 EOS 的外周免疫细胞。此外，免疫特征基因和细胞有望成为 SCZ 的诊断标记和治疗靶点。

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引用次数: 0

The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum 新生儿卡介苗接种对恶性疟原虫体外细胞因子反应的影响

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-04-30 DOI: 10.1186/s12865-024-00611-5

NL Messina, M Wang, EK Forbes, B Freyne, WP Hasang, S Germano, R Bonnici, F Summons, K Gardiner, S Donath, R Gordon, SJ Rogerson, N Curtis

Bacillus Calmette–Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.

卡介苗（Bacillus Calmette-Guérin，BCG）对与结核病无关的感染具有脱靶保护作用。其中，小鼠和人体研究表明，接种卡介苗可预防疟疾。我们研究了卡介苗接种是否会影响新生儿对恶性疟原虫的体外细胞因子反应。我们收集了墨尔本婴儿研究卡介苗减少过敏和感染（MIS BAIR）随机对照试验（临床试验注册号 NCT01906853，2013 年 7 月注册）的 108 名参与者的血样，这些参与者在随机接种新生儿卡介苗（66 人）或未接种卡介苗（42 人）七天后接种卡介苗。用恶性疟原虫感染的红细胞（PfIE）或大肠杆菌刺激后，测量体外细胞因子反应。接种过卡介苗的新生儿和未接种过卡介苗的新生儿在受到恶性疟原虫感染红细胞或大肠杆菌刺激后，所测得的细胞因子没有差异。然而，采血年龄与细胞因子对PfIE反应的改变有独立关联。男性也与新生儿对PfIE和大肠杆菌的TNF-a反应增加有关。这些发现并不支持卡介苗接种在影响新生儿对恶性疟原虫的体外细胞因子反应中发挥作用。年龄较大的新生儿更有可能出现恶性疟原虫诱导的IFN-γ和IFN-γ诱导的趋化因子反应，这些反应与早期疟疾防护和疟疾发病机制有关。

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引用次数: 0

Basophil activation in insect venom allergy: comparison of an established test using liquid reagents with a test using 5-color tubes with dried antibody reagents 昆虫毒液过敏中的嗜碱性粒细胞活化：使用液体试剂的成熟检测方法与使用五色管和干燥抗体试剂的检测方法的比较

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-04-27 DOI: 10.1186/s12865-024-00616-0

Sebastian Waldherr, Miriam Hils, Martin Köberle, Knut Brockow, Ulf Darsow, Simon Blank, Tilo Biedermann, Bernadette Eberlein

Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagents while a new development involves the use of tubes with dried antibody reagents. The aim of this pilot study was to compare these two techniques in patients with insect venom allergy. Seventeen patients with an insect venom allergy were included in the study. The established “BAT 1” utilizes conventional antibody solutions of anti-CCR3 for basophil identification and anti-CD63 to assess basophil activation, whereas “BAT 2” uses dried anti-CD45, anti-CD3, anti-CRTH2, anti-203c and anti-CD63 for identification and activation measurement of basophils. Negative and positive controls as well as incubations with honey bee venom and yellow jacket venom at three concentrations were performed. Seven patients had to be excluded due to low basophil counts, high values in negative controls or negative positive controls. For the remaining 10 patients the overall mean (± SD) difference in activated basophils between the two tests was 0.2 (± 12.2) %P. In a Bland-Altman plot, the limit of agreement (LoA) ranged from 24.0 to -23.7. In the qualitative evaluation (value below/above cut-off) Cohen’s kappa was 0.77 indicating substantial agreement. BAT 2 took longer to perform than BAT 1 and was more expensive. The BAT 2 technique represents an interesting innovation, however, it was found to be less suitable compared to an established BAT for the routine diagnosis of insect venom allergies.

基于流式细胞仪的嗜碱性粒细胞活化检测（BAT）在使用不同的识别和活化标记物方面有各种不同的改进。成熟的测试使用液体试剂，而新开发的测试则使用带有干燥抗体试剂的试管。这项试验性研究的目的是在昆虫毒液过敏患者中比较这两种技术。17 名昆虫毒液过敏患者参与了这项研究。已建立的 "BAT 1 "使用传统的抗-CCR3 抗体溶液来鉴定嗜碱性粒细胞，并使用抗-CD63 来评估嗜碱性粒细胞的活化情况；而 "BAT 2 "则使用干燥的抗-CD45、抗-CD3、抗-CRTH2、抗-203c 和抗-CD63 来鉴定和测量嗜碱性粒细胞的活化情况。此外，还进行了阴性和阳性对照以及三种浓度的蜜蜂毒液和黄夹克毒液培养。由于嗜碱性粒细胞计数偏低、阴性对照组数值偏高或阳性对照组为阴性，有七名患者被排除在外。其余 10 名患者的嗜碱性粒细胞活化率在两次试验中的总平均值（± SD）差异为 0.2 (± 12.2) %P。在 Bland-Altman 图中，一致性极限（LoA）在 24.0 到 -23.7 之间。在定性评估（低于/高于临界值）中，科恩卡帕值为 0.77，表明两者的一致性很高。BAT 2 比 BAT 1 耗时更长，成本更高。BAT 2 技术是一项有趣的创新，但与成熟的 BAT 相比，它不太适合用于昆虫毒液过敏的常规诊断。

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引用次数: 0

Advanced in immunological monitoring of HIV infection: profile of immune cells and cytokines in people living with HIV-1 in Benin 艾滋病毒感染免疫学监测方面的先进技术：贝宁艾滋病毒-1 感染者的免疫细胞和细胞因子概况

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-04-20 DOI: 10.1186/s12865-024-00615-1

Yaou Pierrot Assogba, Adefounke Prudencia Adechina, Edmond Tchiakpe, Odilon Paterne Nouatin, René K. Kèkè, Moussa Bachabi, Honoré Sourou Bankole, Akadiri Yessoufou

Immune cells and cytokines have been linked to viremia dynamic and immune status during HIV infection. They may serve as useful biomarkers in the monitoring of people living with HIV-1 (PLHIV-1). The present work was aimed to assess whether cytokines and immune cell profiles may help in the therapeutic follow-up of PLHIV-1. Forty PLHIV-1 in treatment success (PLHIV-1s) and fifty PLHIV-1 in treatment failure (PLHIV-1f) followed at the University Hospital of Abomey-Calavi/Sô-Ava in Benin were enrolled. Twenty healthy persons were also recruited as control group. Circulating cytokines and immune cells were quantified respectively by ELISA and flow cytometry. PLHIV-1 exhibited low proportions of CD4 + T cells, NK, NKT, granulocytes, classical and non-classical monocytes, and high proportions of CD8 + T cells, particularly in the PLHIV-1f group, compared to control subjects. Eosinophils, neutrophils and B cell frequencies did not change between the study groups. Circulating IFN-γ decreased whereas IL-4 significantly increased in PLHIV-1s compared to PLHIV-1f and control subjects even though the HIV infection in PLHIV-1s downregulated the high Th1 phenotype observed in control subjects. However, Th1/Th2 ratio remained biased to a Th1 phenotype in PLHIV-1f, suggesting that high viral load may have maintained a potential pro-inflammatory status in these patients. Data on inflammatory cytokines showed that IL-6 and TNF-α concentrations were significantly higher in PLHIV-1s and PLHIV-1f groups than in control subjects. Significant high levels of IL-5 and IL-7 were observed in PLHIV-1f compared to controls whereas PLHIV-1s presented only a high level of IL-5. No change was observed in IL-13 levels between the study groups. Our study shows that, in addition to CD4/CD8 T cell ratio, NK and NKT cells along with IL-6, TNF-α, IL-5 and IL-7 cytokines could serve as valuable immunological biomarkers in the therapeutic monitoring of PLHIV-1 although a larger number of patients would be necessary to confirm these results.

免疫细胞和细胞因子与艾滋病毒感染期间的病毒血症动态和免疫状态有关。它们可作为监测 HIV-1 感染者（PLHIV-1）的有用生物标志物。本研究旨在评估细胞因子和免疫细胞图谱是否有助于对 PLHIV-1 进行治疗跟踪。在贝宁阿波美-卡拉维/索阿瓦大学医院随访的 40 名治疗成功的 PLHIV-1 (PLHIV-1s) 和 50 名治疗失败的 PLHIV-1 (PLHIV-1f)。另外还招募了 20 名健康人作为对照组。循环细胞因子和免疫细胞分别通过酶联免疫吸附试验和流式细胞术进行量化。与对照组相比，PLHIV-1 组的 CD4 + T 细胞、NK、NKT、粒细胞、经典和非经典单核细胞比例较低，而 CD8 + T 细胞比例较高，尤其是 PLHIV-1f 组。嗜酸性粒细胞、中性粒细胞和 B 细胞的频率在研究组之间没有变化。与 PLHIV-1f 和对照组相比，PLHIV-1s 组的循环 IFN-γ 减少，而 IL-4 则显著增加，尽管 PLHIV-1s 组的艾滋病毒感染降低了对照组的高 Th1 表型。然而，在 PLHIV-1f 中，Th1/Th2 比率仍偏向于 Th1 表型，这表明高病毒载量可能使这些患者保持潜在的促炎状态。炎症细胞因子数据显示，PLHIV-1s 和 PLHIV-1f 组的 IL-6 和 TNF-α 浓度明显高于对照组。与对照组相比，PLHIV-1f 组的 IL-5 和 IL-7 水平明显较高，而 PLHIV-1s 组仅有较高的 IL-5 水平。研究组之间的 IL-13 水平没有变化。我们的研究表明，除了 CD4/CD8 T 细胞比率外，NK 和 NKT 细胞以及 IL-6、TNF-α、IL-5 和 IL-7 细胞因子可作为有价值的免疫生物标志物，用于 PLHIV-1 的治疗监测，尽管需要更多的患者来证实这些结果。

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引用次数: 0

Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis 作为免疫系统调节剂的螺旋藻衍生蛋白：对其缓解结肠炎前景的系统回顾

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-04-18 DOI: 10.1186/s12865-024-00614-2

Maimonah Alghanmi, Faisal Minshawi, Tarfa A. Altorki, Ayat Zawawi, Isra Alsaady, Abdallah Y Naser, Hassan Alwafi, Soa’ad M. Alsulami, Ala A. Azhari, Anwar M Hashem, Rowa Alhabbab

Helminth-derived proteins have immunomodulatory properties, influencing the host’s immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn’s disease.

蠕虫衍生蛋白具有免疫调节特性，可影响宿主的免疫反应，是蠕虫生存的一种适应性策略。螺旋虫衍生蛋白通过诱导抗炎细胞因子、促进调节性T细胞发育以及最终有利于Th2偏向的免疫反应来调节免疫反应。本系统综述重点研究蠕虫衍生蛋白，探讨它们对减轻小鼠结肠炎模型炎症反应的影响。通过对 Medline、EMBASE、Web of Science 和 Cochrane 图书馆进行系统检索，发现了 14 项相关研究。这些研究报告了免疫调节变化，包括抗炎细胞和细胞因子产量的增加。在使用蠕虫衍生蛋白治疗结肠炎的小鼠模型中，与对照组相比，体重、结肠长度和显微炎症评分等病理参数都有显著改善。此外，蠕虫衍生蛋白还能增强Tregs的功能，减轻炎症的严重程度。这些发现强调了蠕虫衍生蛋白在免疫调节中的关键作用，特别是在细胞因子分泌和免疫细胞极化轴中的作用。这些发现为治疗克罗恩病等慢性炎症提供了新的机会。

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引用次数: 0

Association of interleukin-17A and chemokine/vascular endothelial growth factor-induced angiogenesis in newly diagnosed patients with bladder cancer. 新诊断的膀胱癌患者中白细胞介素-17A与趋化因子/血管内皮生长因子诱导的血管生成有关。

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-03-21 DOI: 10.1186/s12865-024-00612-4

Ali Moadab, Mohammad Rafie Valizadeh, Alireza Nazari, Hossein Khorramdelazad

Background: The human interleukin-17 (IL-17) family comprises IL-17A to IL-17 F; their receptors are IL-17RA to IL-17RE. Evidence revealed that these cytokines can have a tumor-supportive or anti-tumor impact on human malignancies. The purpose of this study was to assess the expression of CXCR2, IL-17RA, and IL-17RC genes at the mRNA level as well as tissue and serum levels of IL-17A, vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β) in patients with bladder cancer (BC) compared to control.

Results: This study showed that gene expression of IL-17RA, IL-17RC, and CXCR2 in the tumoral tissue of BC patients was significantly upregulated compared with normal tissue. The findings disclosed a significant difference in the serum and tissue concentrations of IL-17A, VEGF, and TGF-β between the patient and the control groups, as well as tumor and normal tissues.

Conclusion: This study reveals notable dysregulation of CXCR2, IL-17RA, and IL-17RC genes, alongside changes in IL-17A, VEGF, and TGF-β levels in patients with BC than in controls. These findings indicate their possible involvement in BC development and their potential as diagnostic and therapeutic targets.

背景：人类白细胞介素-17（IL-17）家族由 IL-17A 至 IL-17 F 组成，其受体为 IL-17RA 至 IL-17RE。有证据表明，这些细胞因子可对人类恶性肿瘤产生支持或抗肿瘤影响。本研究的目的是评估膀胱癌（BC）患者与对照组相比，CXCR2、IL-17RA 和 IL-17RC 基因在 mRNA 水平上的表达以及组织和血清中 IL-17A、血管内皮生长因子（VEGF）和转化生长因子 β（TGF-β）的水平：研究表明，与正常组织相比，膀胱癌患者肿瘤组织中 IL-17RA、IL-17RC 和 CXCR2 的基因表达明显上调。研究结果表明，IL-17A、血管内皮生长因子和 TGF-β 在患者组与对照组、肿瘤组织与正常组织之间的血清和组织浓度存在明显差异：本研究发现，与对照组相比，BC 患者的 CXCR2、IL-17RA 和 IL-17RC 基因明显失调，同时 IL-17A、VEGF 和 TGF-β 水平也发生了变化。这些发现表明，它们可能参与了 BC 的发展，并有可能成为诊断和治疗目标。

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引用次数: 0

Causal relationship between immune cells and telomere length: mendelian randomization analysis. 免疫细胞与端粒长度之间的因果关系：泯灭随机分析。

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-03-08 DOI: 10.1186/s12865-024-00610-6

Yujian Li, Shenglin Lai, Xuan Kan

Background: The causal relationship between immune cells and telomere length remains controversial.

Methods: Data on the immune cells were obtained from a previous study with 3,757 participants. Data on telomere length were obtained from the OpenGWAS database. Genome-Wide Association Study (GWAS) data were obtained and screened for eligible instrumental variables (IVs) using the TwoSampleMR package and the Phenoscanner database. To investigate the genetic causality between immune cells and telomere length, Mendelian randomization (MR) analysis and Bayesian weighted Mendelian randomization (BWMR) analysis were used.

Results: MR analysis showed that there is indeed a genetic causal relationship between immune cells and telomere length. A total of 16 immune cells were successfully validated. A positive correlation was found between telomere length and immune cells such as CD28 + CD45RA + CD8br %CD8br (OR = 1.002, 95%CI: 1.000-1.003). A negative correlation was found between telomere length and immune cells such as Transitional AC (OR = 0.991, 95%CI: 0.984-0.997) (P < 0.05). Reverse MR analysis similarly confirmed that telomere length can affect four types of immune cells, including CD25 on IgD + CD24- (OR = 1.291, 95%CI: 1.060-1.571), at the genetic level.

Conclusion: There is indeed a mutual genetic causality between immune cells and telomere length, which will provide theoretical basis and support for more subsequent clinical studies.

背景：免疫细胞与端粒长度之间的因果关系仍存在争议：免疫细胞与端粒长度之间的因果关系仍存在争议：免疫细胞的数据来自于之前一项有 3757 名参与者参与的研究。端粒长度的数据来自 OpenGWAS 数据库。利用TwoSampleMR软件包和Phenoscanner数据库获取了全基因组关联研究（GWAS）数据，并筛选出符合条件的工具变量（IV）。为了研究免疫细胞与端粒长度之间的遗传因果关系，采用了孟德尔随机（MR）分析和贝叶斯加权孟德尔随机（BWMR）分析：MR分析表明，免疫细胞与端粒长度之间确实存在遗传因果关系。共有 16 种免疫细胞被成功验证。端粒长度与免疫细胞（如 CD28 + CD45RA + CD8br %CD8br）之间呈正相关（OR = 1.002，95%CI：1.000-1.003）。端粒长度与免疫细胞（如过渡性 AC）之间呈负相关（OR = 0.991，95%CI：0.984-0.997）（P 结论：端粒长度与免疫细胞（如过渡性 AC）之间确实存在遗传上的互为因果关系：免疫细胞与端粒长度之间确实存在相互的遗传因果关系，这将为后续更多的临床研究提供理论依据和支持。

{"title":"Causal relationship between immune cells and telomere length: mendelian randomization analysis.","authors":"Yujian Li, Shenglin Lai, Xuan Kan","doi":"10.1186/s12865-024-00610-6","DOIUrl":"10.1186/s12865-024-00610-6","url":null,"abstract":"Background: The causal relationship between immune cells and telomere length remains controversial.Methods: Data on the immune cells were obtained from a previous study with 3,757 participants. Data on telomere length were obtained from the OpenGWAS database. Genome-Wide Association Study (GWAS) data were obtained and screened for eligible instrumental variables (IVs) using the TwoSampleMR package and the Phenoscanner database. To investigate the genetic causality between immune cells and telomere length, Mendelian randomization (MR) analysis and Bayesian weighted Mendelian randomization (BWMR) analysis were used.Results: MR analysis showed that there is indeed a genetic causal relationship between immune cells and telomere length. A total of 16 immune cells were successfully validated. A positive correlation was found between telomere length and immune cells such as CD28 + CD45RA + CD8br %CD8br (OR = 1.002, 95%CI: 1.000-1.003). A negative correlation was found between telomere length and immune cells such as Transitional AC (OR = 0.991, 95%CI: 0.984-0.997) (P < 0.05). Reverse MR analysis similarly confirmed that telomere length can affect four types of immune cells, including CD25 on IgD + CD24- (OR = 1.291, 95%CI: 1.060-1.571), at the genetic level.Conclusion: There is indeed a mutual genetic causality between immune cells and telomere length, which will provide theoretical basis and support for more subsequent clinical studies.","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"19"},"PeriodicalIF":3.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140064779","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

Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes. 免疫缺陷患者的皮下免疫球蛋白替代疗法--药物包装和给药方法对患者报告结果的影响。

IF 3 4区医学 Q3 IMMUNOLOGY

BMC Immunology

Pub Date : 2024-02-20 DOI: 10.1186/s12865-024-00608-0

R Mallick, G Solomon, P Bassett, X Zhang, P Patel, O Lepeshkina

Background: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared.

Methods: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push).

Results: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02).

Conclusions: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

背景：方法：魁北克免疫缺陷患者协会（APIQ）于 2020 年 10 月至 2021 年 3 月在加拿大进行了一项在线调查：魁北克免疫缺陷患者协会（APIQ）在加拿大开展了一项在线调查（10/2020-03/2021）。调查问题包括：选择 SCIg 包装和给药方法的原因、培训经历、输液特点和转换方法。调查收集了患者报告的结构性结果：治疗满意度及其子域、症状状态、总体健康感知以及身心功能。将使用 PFS 的受访者与使用药瓶的受访者进行了整体比较，并按其给药方法（泵或手动推注）进行了分层：结果：在总共 132 位受访者中，66 位受访者使用小瓶，38 位使用泵，28 位使用手推。120 名受访者使用 PFS（5 毫升和 10 毫升规格），其中 38 人使用泵，82 人使用手推式。与使用药瓶的受访者相比，PFS 使用者的 SCIg 剂量中位数（四分位数间距）低 17%（分别为 10 [8, 12] vs. 12 [9, 16] g/周），输液准备时间显著缩短（分别为 15 [10, 20] vs. 15 [10, 30] 分钟），输液时间有缩短的趋势（分别为 60 [35, 90] vs. 70 [48, 90] 分钟）。患者报告的治疗满意度得分在小瓶和 PFS 使用者之间总体相似（包括有效性和便利性方面），但在总体满意度方面，小瓶的得分高于 PFS（P=0.02）：结论：PFS 使用者的 SCIg 剂量明显低于小瓶使用者，这与处方中减少浪费的理念一致。PFS 使用者的预输液时间也更短，这反映出与小瓶使用者相比，PFS 使用者的给药方法更简单。与 PFS 使用者相比，小瓶使用者对治疗的总体满意度更高，这与研究期间加拿大的使用者只能选择较小的 PFS 规格是一致的。随着更大规格 PFS 的推出，患者对 PFS 的体验有望得到改善。总体而言，采用 PFS 包装后，SCIg 的治疗满意度始终高于小瓶包装。

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引用次数: 0