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Inhibition of CEACAM1 expression in cytokine-activated neutrophils using JAK inhibitors. 使用 JAK 抑制剂抑制细胞因子激活的中性粒细胞中 CEACAM1 的表达。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12865-024-00656-6
Haruki Matsumoto, Ryota Sudo, Yuya Fujita, Michio Onizawa, Kenji Saito, Yuya Sumichika, Shuhei Yoshida, Jumpei Temmoku, Naoki Matsuoka, Tomoyuki Asano, Shuzo Sato, Eiji Suzuki, Takeshi Machida, Kiyoshi Migita

Objectives: Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We previously demonstrated that CEACAM1 is predominantly expressed on peripheral blood neutrophils in patients with RA. The aim of the present study was to investigate the effects of Janus kinase inhibitors (JAKi) on cytokine-activated human neutrophils and CEACAM1 expression.

Methods: Peripheral blood neutrophils were obtained from healthy subjects. Isolated neutrophils were stimulated with tumor necrosis factor-alpha (TNF-α) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence or absence of JAKi. The expression of CEACAM1 in peripheral blood neutrophils was analyzed by flow cytometry. Protein phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 was assessed by western blot using phospho-specific antibodies.

Results: We found that TNF-α-induced CEACAM1 expression was marginally suppressed after pretreatment with pan-JAK inhibitor, tofacitinib. Moreover, TNF-α induced STAT1 and STAT3 phosphorylation at the late stimulation phase (4 to 16 h). The expressions of CEACAM1 on neutrophils were markedly up-regulated by GM-CSF not by interleukin (IL)-6 stimulation. All JAKi inhibited GM-CSF-induced CEACAM1 expressions on neutrophils, however, the inhibitory effects of baricitinib were larger compared to those of tofacitinib or filgotinib. Moreover, CEACAM1 was marginally upregulated in interferon (IFN)-γ stimulated neutrophils. Similarly, JAKi inhibited IFN-γ-induced CEACAM1 expressions on neutrophils.

Conclusions: We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

研究目的癌胚抗原相关细胞粘附分子 1(CEACAM1)是一种粘附分子,在免疫系统中充当共抑制受体。我们曾证实 CEACAM1 主要表达于 RA 患者的外周血中性粒细胞。本研究旨在探讨Janus激酶抑制剂(JAKi)对细胞因子激活的人中性粒细胞和CEACAM1表达的影响:方法:从健康受试者处获取外周血中性粒细胞。在有或没有 JAKi 的情况下,用肿瘤坏死因子-α(TNF-α)或粒细胞-巨噬细胞集落刺激因子(GM-CSF)刺激分离的中性粒细胞。流式细胞术分析了外周血中性粒细胞中 CEACAM1 的表达。使用磷酸化特异性抗体通过 Western 印迹评估信号转导和转录激活因子(STAT)1、STAT3 和 STAT5 的蛋白磷酸化:结果:我们发现,TNF-α诱导的CEACAM1表达在使用泛JAK抑制剂托法替尼预处理后略有抑制。此外,TNF-α在刺激后期(4-16 h)诱导STAT1和STAT3磷酸化。中性粒细胞上的 CEACAM1 的表达在 GM-CSF 而非白细胞介素(IL)-6 的刺激下明显上调。所有JAKi都能抑制GM-CSF诱导的CEACAM1在中性粒细胞上的表达,但巴利昔替尼的抑制作用大于托法替尼和非格替尼。此外,CEACAM1在干扰素(IFN)-γ刺激的中性粒细胞中略有上调。同样,JAKi抑制了IFN-γ诱导的中性粒细胞上CEACAM1的表达:我们证实,JAKi能阻止GM-CSF诱导的CEACAM1在中性粒细胞中的表达,而JAKi诱导的抑制作用取决于其对JAK同工酶的选择性。这些发现表明,JAKi 可调节细胞因子激活的中性粒细胞中 CEACAM1 的表达,从而限制其活化。
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引用次数: 0
Autoimmunity's enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome. 自身免疫的神秘作用:探索与肌痛性脑脊髓炎/慢性疲劳综合征的联系。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12865-024-00657-5
Jacob Batham, Jessica Dwyer, Natalie Eaton-Fitch, Sonya Marshall-Gradisnik

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complicated, heterogeneous condition distinguished by post-exertional neuroimmune exhaustion and multisystem symptoms. Its complexity poses challenges for physicians, researchers and those inflicted by its presence. Due to conflicting evidence and limiting consensus, the association and contribution autoimmunity serves in the pathophysiology or aetiology of ME/CFS is yet to be confirmed. This systematic review synthesises the currently available data to clarify the role autoimmunity has in the pathogenesis of ME/CFS and explore the therapeutic limitations.

Methods: This systematic review was conducted in accordance with the PRISMA and Cochrane guidelines. Full-text articles containing the primary key terms "Autoimmunity/Autoimmune" and "ME/CFS" were included provided their suitability to the inclusion and exclusion criteria.

Results: Ten publications investigating the role of autoimmunity in ME/CFS were examined. One investigated the role of cytokine signalling; Three investigated the genetic nature of autoimmunity in ME/CFS patients; One examined the immune lineage of ME/CFS patients; Six investigated the presence and role of autoantibodies in ME/CFS patients.

Conclusion: The findings generated from this systematic review highlight inconsistent and insufficient evidence to classify ME/CFS as an autoimmune disease. Additionally, it further emphasises the complexity of ME/CFS and highlights the challenges in distinguishing autoreactivity from deregulatory processes. Future research is urgently needed to advance the development of diagnostic and treatment strategies.

Prospero registration code: CRD42024533447.

背景:肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种复杂的异质性疾病,以运动后神经免疫衰竭和多系统症状为特征。它的复杂性给医生、研究人员和患者带来了挑战。由于证据相互矛盾、共识有限,自身免疫在 ME/CFS 病理生理学或病因学中的关联和作用仍有待证实。本系统性综述综合了目前可用的数据,以阐明自身免疫在 ME/CFS 发病机制中的作用,并探讨其治疗局限性:本系统综述根据 PRISMA 和 Cochrane 指南进行。只要符合纳入和排除标准,就会纳入包含主要关键词 "自身免疫/自身免疫 "和 "ME/CFS "的全文文章:结果:研究了10篇调查自身免疫在ME/CFS中作用的文章。其中一篇研究了细胞因子信号的作用;三篇研究了ME/CFS患者自身免疫的遗传性质;一篇研究了ME/CFS患者的免疫系统;六篇研究了ME/CFS患者自身抗体的存在和作用:本系统综述的研究结果表明,将ME/CFS归类为自身免疫性疾病的证据并不一致,也不充分。此外,它还进一步强调了ME/CFS的复杂性,并突出了区分自身反应和失调过程所面临的挑战。未来迫切需要开展研究,以推动诊断和治疗策略的发展:CRD42024533447。
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引用次数: 0
Convergence of endothelial dysfunction, inflammation and glucocorticoid resistance in depression-related cardiovascular diseases. 抑郁症相关心血管疾病中内皮功能障碍、炎症和糖皮质激素抵抗的汇合。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-27 DOI: 10.1186/s12865-024-00653-9
Zachary Hage, Miguel M Madeira, Dimitris Koliatsis, Stella E Tsirka

Major Depressive Disorder, or depression, has been extensively linked to dysregulated HPA axis function, chronic inflammation and cardiovascular diseases. While the former two have been studied in depth, the mechanistic connection between depression and cardiovascular disease is unclear. As major mediators of vascular homeostasis, vascular pathology and immune activity, endothelial cells represent an important player connecting the diseases. Exaggerated inflammation and glucocorticoid function are important topics to explore in the endothelial response to MDD. Glucocorticoid resistance in several cell types strongly promotes inflammatory signaling and results in worsened severity in many diseases. However, endothelial health and inflammation in chronic stress and depression are rarely considered from the perspective of glucocorticoid signaling and resistance. In this review, we aim to discuss (1) endothelial dysfunction in depression, (2) inflammation in depression, (3) general glucocorticoid resistance in depression and (4) endothelial glucocorticoid resistance in depression co-morbid inflammatory diseases. We will first describe vascular pathology, inflammation and glucocorticoid resistance separately in depression and then describe their potential interactions with one another in depression-relevant diseases. Lastly, we will hypothesize potential mechanisms by which glucocorticoid resistance in endothelial cells may contribute to vascular disease states in depressed people. Overall, endothelial-glucocorticoid signaling may play an important role in connecting depression and vascular pathology and warrants further study.

重度抑郁症(抑郁症)与 HPA 轴功能失调、慢性炎症和心血管疾病有着广泛的联系。虽然对前两者进行了深入研究,但抑郁症与心血管疾病之间的机理联系尚不清楚。作为血管稳态、血管病理和免疫活动的主要介质,内皮细胞是连接这些疾病的重要角色。炎症加剧和糖皮质激素功能是探讨内皮细胞对多发性硬化症反应的重要课题。几种细胞类型的糖皮质激素抗性会强烈促进炎症信号转导,导致许多疾病的严重程度恶化。然而,人们很少从糖皮质激素信号传导和抵抗的角度来考虑慢性应激和抑郁症中的内皮健康和炎症问题。在这篇综述中,我们旨在讨论:(1) 抑郁症的内皮功能障碍;(2) 抑郁症的炎症;(3) 抑郁症的一般糖皮质激素抵抗;(4) 抑郁症合并炎症性疾病的内皮糖皮质激素抵抗。我们将首先分别描述抑郁症中的血管病理学、炎症和糖皮质激素抵抗,然后描述它们在抑郁症相关疾病中的潜在相互作用。最后,我们将假设内皮细胞的糖皮质激素抵抗可能导致抑郁症患者血管疾病状态的潜在机制。总之,内皮细胞-糖皮质激素信号传导可能在连接抑郁症和血管病理学方面发挥重要作用,值得进一步研究。
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引用次数: 0
β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer β-葡聚糖与恩伐利单抗和 Endostar 联合作为转移性非小细胞肺癌的免疫再挑战疗法
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-14 DOI: 10.1186/s12865-024-00651-x
Qian Geng, Yingying Lu, Dongqing Li, Lanqun Qin, Chunjian Qi, Xiaolin Pu, Yi Zhuang, Yajun Zhu, Quanbin Zha, Ge Wang, Hua Jiang
Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months [95% CI: 7.2–12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.
免疫检查点抑制剂再挑战已成为非小细胞肺癌(NSCLC)的一个重要研究领域。据报道,β-葡聚糖可通过调节肿瘤微环境来逆转抗PD-1/PD-L1抑制剂的耐药性。在这项自发的临床试验(ChiCTR2100054796)中,既往抗PD-1治疗失败的NSCLC参与者每3周接受一次β-葡聚糖(500毫克,bid,d1-21)、恩华利单抗(300毫克,d1)和Endostar(210毫克,civ72h)治疗,直至疾病进展或出现不可接受的毒性。观察临床疗效和不良反应,同时收集血清样本进行蛋白质组分析。从 2022 年 1 月到 2023 年 3 月,共招募了 23 名患者(中位年龄 65 岁;男性,n = 18 [78.3%];鳞状 NSCLC,n = 9 [39.1%];突变型,n = 13 [56.5%])。总反应率(ORR)为21.7%,疾病控制率(DCR)为73.9%。中位无进展生存期(mPFS)和中位总生存期(mOS)分别为4.3个月[95% CI:2.0-6.6]和9.8个月[95% CI:7.2-12.4]。PD-L1阳性亚组和阴性亚组的mPFS差异显著(6.3个月 vs. 2.3个月,P = 0.002)。52.2%的患者发生了治疗相关不良事件(TRAEs)。最常见的不良反应是甲状腺功能减退(26.1%)和疲劳(26.1%)。报告了 2 例(8.7%)3 级不良反应。未发现与不良反应相关的死亡病例。蛋白质组分析显示,CASP-8、ARG1、MMP12、CD28和CXCL5的水平与治疗耐药性相关,而CD40-L和EGF的水平与良好反应相关。β-葡聚糖与恩伐利单抗和恩度斯达联合治疗既往抗PD-1治疗失败的转移性NSCLC患者,尤其是PD-L1阳性患者的免疫再挑战具有相当高的疗效和安全性。
{"title":"β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer","authors":"Qian Geng, Yingying Lu, Dongqing Li, Lanqun Qin, Chunjian Qi, Xiaolin Pu, Yi Zhuang, Yajun Zhu, Quanbin Zha, Ge Wang, Hua Jiang","doi":"10.1186/s12865-024-00651-x","DOIUrl":"https://doi.org/10.1186/s12865-024-00651-x","url":null,"abstract":"Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months [95% CI: 7.2–12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From bioinformatics to clinical applications: a novel prognostic model of cuproptosis-related genes based on single-cell RNA sequencing data in hepatocellular carcinoma 从生物信息学到临床应用:基于肝细胞癌单细胞 RNA 测序数据的杯突症相关基因的新型预后模型
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-09 DOI: 10.1186/s12865-024-00649-5
Yong Wang, Fenglin Zang, Bing Shao, Yanan Gao, Haicui Yang, Yuhong Guo, Tingting Ding, Baocun Sun
To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database. Thirty-three DE-CRGs in HCC were identified. A prognostic model (PM) was created employing six survival-related genes (SRGs) (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) via univariate Cox regression analysis and LASSO. The predictive ability of the model was validated via a nomogram and receiver operating characteristic curves. Research has employed tumor immune dysfunction and exclusion as a means to examine the influence of PM on immunological heterogeneity. Macrophage M0 levels were significantly different between the high-risk group (HRG) and the low-risk group (LRG), and a greater macrophage level was linked to a more unfavorable prognosis. The drug sensitivity data indicated a substantial difference in the half-maximal drug-suppressive concentrations of idarubicin and rapamycin between the HRG and the LRG. The model was verified by employing public datasets and our cohort at both the protein and mRNA levels. A PM using 6 SRGs (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) was developed via bioinformatics research. This model might provide a fresh perspective for assessing and managing HCC.
为了通过单细胞RNA测序(scRNA-seq)和RNA测序(RNA-seq)数据确定杯突相关基因(CRGs)与肝细胞癌(HCC)预后之间的联系,研究人员从GEO和TCGA数据库下载了相关数据。根据scRNA-seq数据库中HCC患者与正常对照组(NCs)之间差异表达基因(DEGs)的重叠、高CRG活性细胞与低CRG活性细胞之间的DE-CRGs以及TCGA数据库中HCC患者与NCs之间的DEGs,筛选出差异表达的CRGs(DE-CRGs)。结果发现了 HCC 中的 33 个 DE-CRG。通过单变量 Cox 回归分析和 LASSO,利用六个生存相关基因(SRGs)(NDRG2、CYB5A、SOX4、MYC、TM4SF1 和 IFI27)创建了一个预后模型(PM)。该模型的预测能力通过提名图和接收者操作特征曲线得到了验证。有研究利用肿瘤免疫功能障碍和排斥作为研究 PM 对免疫异质性影响的一种手段。巨噬细胞M0水平在高危组(HRG)和低危组(LRG)之间存在显著差异,巨噬细胞水平越高,预后越差。药物敏感性数据显示,伊达比星和雷帕霉素的半最大药物抑制浓度在高危组和低危组之间存在很大差异。该模型通过使用公共数据集和我们的队列在蛋白质和 mRNA 水平上进行了验证。通过生物信息学研究,利用 6 个 SRG(NDRG2、CYB5A、SOX4、MYC、TM4SF1 和 IFI27)建立了一个 PM。该模型可为评估和管理 HCC 提供新的视角。
{"title":"From bioinformatics to clinical applications: a novel prognostic model of cuproptosis-related genes based on single-cell RNA sequencing data in hepatocellular carcinoma","authors":"Yong Wang, Fenglin Zang, Bing Shao, Yanan Gao, Haicui Yang, Yuhong Guo, Tingting Ding, Baocun Sun","doi":"10.1186/s12865-024-00649-5","DOIUrl":"https://doi.org/10.1186/s12865-024-00649-5","url":null,"abstract":"To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database. Thirty-three DE-CRGs in HCC were identified. A prognostic model (PM) was created employing six survival-related genes (SRGs) (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) via univariate Cox regression analysis and LASSO. The predictive ability of the model was validated via a nomogram and receiver operating characteristic curves. Research has employed tumor immune dysfunction and exclusion as a means to examine the influence of PM on immunological heterogeneity. Macrophage M0 levels were significantly different between the high-risk group (HRG) and the low-risk group (LRG), and a greater macrophage level was linked to a more unfavorable prognosis. The drug sensitivity data indicated a substantial difference in the half-maximal drug-suppressive concentrations of idarubicin and rapamycin between the HRG and the LRG. The model was verified by employing public datasets and our cohort at both the protein and mRNA levels. A PM using 6 SRGs (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) was developed via bioinformatics research. This model might provide a fresh perspective for assessing and managing HCC.","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revised version with tracked changes oral Magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus. 修订版口服镁可降低小鼠狼疮的致病性自身抗体水平和皮肤病。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-06 DOI: 10.1186/s12865-024-00650-y
Alberto Verlato, Teresina Laragione, Sofia Bin, Randie H Kim, Fadi Salem, Percio S Gulko, Paolo Cravedi

Background: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping.

Results: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology.

Conclusion: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.

背景:系统性红斑狼疮(SLE)有很强的遗传易感性,但人们对饮食对疾病严重程度的影响知之甚少。西方饮食中通常缺乏镁(Mg),鉴于镁具有免疫调节作用,我们假设镁摄入量低会增加患病风险,而增加镁摄入量会降低小鼠狼疮的严重程度。在这里,我们将 12 周大的 MRL/lpr 雌性狼疮小鼠置于正常(Mg500)或高(Mg2800)镁饮食中 9 周。研究期间收集尿液和血液,以定量检测尿白蛋白、BUN、抗dsDNA抗体和免疫表型:结果:与 Mg500 组(143.8±75.0 vs. 47.4±36.2 × 106U/ml;P +FOXP3+ Treg 细胞与对照组相比(19.9±5.4 vs. 11.4±5.5%;P)相比,MRL/lpr 狼疮小鼠摄入高 Mg2800 食物后,皮肤病变显著减少,皮肤组织学评分较轻,致病性抗dsDNA 抗体水平降低:总之,口服补充镁对小鼠狼疮模型有保护作用,可能是治疗 SLsE 的一种廉价、安全的辅助疗法。
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引用次数: 0
Sepsis induced dysfunction of liver type 1 innate lymphoid cells. 败血症导致肝脏 1 型先天性淋巴细胞功能失调。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-30 DOI: 10.1186/s12865-024-00648-6
Peiying Wang, Yiran Zheng, Jiaman Sun, Yumo Zhang, Wing Keung Chan, Yan Lu, Xiaohong Li, Zhouxin Yang, Youwei Wang

Background: Sepsis is a life-threatening condition triggered by uncontrolled immune responses to infection, leading to widespread inflammation, tissue damage, organ dysfunction, and potentially death. The liver plays a crucial role in the immune response during sepsis, serving as a major site for immune cell activation and cytokine production. Liver type 1 innate lymphoid cells (ILCs) consist of NK cells and ILC1s. They maintain the local immune microenvironment by directly eliminating target cells and secreting cytokines. However, the specific roles and pathological changes of liver-resident NK cells and ILC1s during sepsis remain poorly understood.

Results: This study aims to investigate the pathological changes of NK cells and ILC1s, which might contribute the dysfunction of liver. Sepsis mouse model was established by cecal ligation and puncture (CLP). Mouse immune cells from liver were isolated, and the surface makers, gene expression profiles, cytokine response and secretion, and mitochondrial function of NK (Natural Killer) cells and ILC1s (Innate Lymphoid Cell 1) were analyzed. A significant decrease in the number of mature NK cells was observed in the liver after CLP. Furthermore, the secretion of interferon-gamma (IFN-γ) was found to be reduced in spleen and liver NK cells when stimulated by IL-18. Mitochondrial activities in both liver NK cells and ILC1 were found to be increased during sepsis, suggesting an enhanced metabolic response in these cells to combat the infection. However, despite this heightened activity, liver NK cells exhibited a decreased level of cytotoxicity, which might impact their ability to target infected cells effectively. RNA sequencing supported and provided the potential mechanisms for the proinflammatory effects and exhaustion like phenotypes of liver NK cells.

Conclusions: Sepsis induces dysfunction and exhaustion-like phenotypes in liver NK cells and ILC1, which might further impair other immune cells and represent a potential therapeutic target for sepsis.

背景:败血症是一种危及生命的疾病,由感染后失控的免疫反应引发,导致广泛的炎症、组织损伤、器官功能障碍,甚至可能导致死亡。肝脏在败血症期间的免疫反应中起着至关重要的作用,是免疫细胞活化和细胞因子产生的主要场所。肝脏 1 型先天性淋巴细胞(ILCs)由 NK 细胞和 ILC1s 组成。它们通过直接消灭靶细胞和分泌细胞因子来维持局部免疫微环境。然而,人们对肝脏驻留的 NK 细胞和 ILC1s 在败血症期间的具体作用和病理变化仍知之甚少:本研究旨在探讨可能导致肝脏功能障碍的 NK 细胞和 ILC1s 的病理变化。通过盲肠结扎建立败血症小鼠模型。从肝脏中分离出小鼠免疫细胞,分析了NK(自然杀伤细胞)和ILC1s(先天淋巴细胞1)的表面形态、基因表达谱、细胞因子反应和分泌以及线粒体功能。观察发现,CLP 后肝脏中成熟 NK 细胞的数量明显减少。此外,在 IL-18 的刺激下,发现脾脏和肝脏 NK 细胞分泌的干扰素-γ(IFN-γ)减少。在败血症期间,肝脏 NK 细胞和 ILC1 的线粒体活性都有所增加,这表明这些细胞的新陈代谢反应增强,以对抗感染。然而,尽管肝脏NK细胞的活性增强了,但它们的细胞毒性却降低了,这可能会影响它们有效靶向受感染细胞的能力。RNA测序支持并提供了肝脏NK细胞促炎效应和衰竭表型的潜在机制:脓毒症会诱导肝脏NK细胞和ILC1出现功能障碍和衰竭样表型,这可能会进一步损害其他免疫细胞,并成为脓毒症的潜在治疗靶点。
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引用次数: 0
Antagonist anti-LIF antibody derived from naive human scFv phage library inhibited tumor growth in mice. 从天真人类 scFv 噬菌体库中提取的拮抗剂抗 LIF 抗体抑制了小鼠的肿瘤生长。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-22 DOI: 10.1186/s12865-024-00636-w
Shengyan Zhao, Han Deng, Ying Lu, Yiran Tao, David Li, Xiaohua Jiang, Xian Wei, Xiaofeng Chen, Fanxin Ma, Yuxi Wang, Lantu Gou, Jinliang Yang

Background: Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surface. Previous research has shown that LIF is highly expressed in various tumor tissues (e.g. pancreatic cancer, breast cancer, prostate cancer, and colorectal cancer) and promotes cancer cell proliferation, migration, invasion, and differentiation. Moreover, the overexpression of LIF correlates with poor clinicopathological characteristics. Therefore, we hypothesized that LIF could be a promising target for the treatment of cancer. In this work, we developed the antagonist antibody 1G11 against LIF and investigated its anti-tumor mechanism and its therapeutic efficacy in mouse models.

Results: A series of single-chain variable fragments (scFvs) targeting LIF were screened from a naive human scFv phage library. These scFvs were reconstructed in complete IgG form and produced by the mammalian transient expression system. Among the antibodies, 1G11 exhibited the excellent binding activity to human, cynomolgus monkey and mouse LIF. Functional analysis demonstrated 1G11 could block LIF binding to LIFR and inhibit the intracellular STAT3 phosphorylation signal. Interestingly, 1G11 did not block LIF binding to gp130, another LIF receptor that is involved in forming the receptor complex together with LIFR. In vivo, intraperitoneal administration of 1G11 inhibited tumor growth in CT26 and MC38 models of colorectal cancer. IHC analysis demonstrated that p-STAT3 and Ki67 were decreased in tumor tissue, while c-caspase 3 was increased. Furthermore, 1G11 treatment improves CD3+, CD4 + and CD8 + T cell infiltration in tumor tissue.

Conclusions: We developed antagonist antibodies targeting LIF/LIFR signaling pathway from a naive human scFv phage library. Antagonist anti-LIF antibody exerts antitumor effects by specifically reducing p-STAT3. Further studies revealed that anti-LIF antibody 1G11 increased immune cell infiltration in tumor tissues.

背景:白血病抑制因子(LIF)是 IL-6 细胞因子家族的多功能成员,它通过与细胞表面由 LIFR 和 gp130 组成的异二聚体结合激活下游信号通路。以往的研究表明,LIF 在多种肿瘤组织(如胰腺癌、乳腺癌、前列腺癌和结直肠癌)中高表达,并促进癌细胞增殖、迁移、侵袭和分化。此外,LIF 的过表达与不良的临床病理特征相关。因此,我们推测 LIF 可能是治疗癌症的一个有前途的靶点。在这项工作中,我们开发了针对 LIF 的拮抗剂抗体 1G11,并在小鼠模型中研究了其抗肿瘤机制和疗效:结果:从天真的人类 scFv 噬菌体文库中筛选出了一系列靶向 LIF 的单链可变片段(scFvs)。这些 scFvs 被重构为完整的 IgG 形式,并由哺乳动物瞬时表达系统生产。在这些抗体中,1G11 与人类、猴和小鼠 LIF 的结合活性极佳。功能分析表明,1G11 能阻断 LIF 与 LIFR 的结合,抑制细胞内 STAT3 磷酸化信号。有趣的是,1G11 并不阻断 LIF 与 gp130 的结合,gp130 是另一种 LIF 受体,与 LIFR 一起参与形成受体复合物。在体内,腹腔注射 1G11 可抑制 CT26 和 MC38 结直肠癌模型的肿瘤生长。IHC分析表明,肿瘤组织中的p-STAT3和Ki67降低,而c-caspase 3升高。此外,1G11治疗可改善肿瘤组织中CD3+、CD4+和CD8+T细胞的浸润:我们从天真人类scFv噬菌体文库中开发出了靶向LIF/LIFR信号通路的拮抗剂抗体。拮抗剂抗 LIF 抗体通过特异性降低 p-STAT3 发挥抗肿瘤作用。进一步研究发现,抗LIF抗体1G11增加了肿瘤组织中免疫细胞的浸润。
{"title":"Antagonist anti-LIF antibody derived from naive human scFv phage library inhibited tumor growth in mice.","authors":"Shengyan Zhao, Han Deng, Ying Lu, Yiran Tao, David Li, Xiaohua Jiang, Xian Wei, Xiaofeng Chen, Fanxin Ma, Yuxi Wang, Lantu Gou, Jinliang Yang","doi":"10.1186/s12865-024-00636-w","DOIUrl":"10.1186/s12865-024-00636-w","url":null,"abstract":"<p><strong>Background: </strong>Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surface. Previous research has shown that LIF is highly expressed in various tumor tissues (e.g. pancreatic cancer, breast cancer, prostate cancer, and colorectal cancer) and promotes cancer cell proliferation, migration, invasion, and differentiation. Moreover, the overexpression of LIF correlates with poor clinicopathological characteristics. Therefore, we hypothesized that LIF could be a promising target for the treatment of cancer. In this work, we developed the antagonist antibody 1G11 against LIF and investigated its anti-tumor mechanism and its therapeutic efficacy in mouse models.</p><p><strong>Results: </strong>A series of single-chain variable fragments (scFvs) targeting LIF were screened from a naive human scFv phage library. These scFvs were reconstructed in complete IgG form and produced by the mammalian transient expression system. Among the antibodies, 1G11 exhibited the excellent binding activity to human, cynomolgus monkey and mouse LIF. Functional analysis demonstrated 1G11 could block LIF binding to LIFR and inhibit the intracellular STAT3 phosphorylation signal. Interestingly, 1G11 did not block LIF binding to gp130, another LIF receptor that is involved in forming the receptor complex together with LIFR. In vivo, intraperitoneal administration of 1G11 inhibited tumor growth in CT26 and MC38 models of colorectal cancer. IHC analysis demonstrated that p-STAT3 and Ki67 were decreased in tumor tissue, while c-caspase 3 was increased. Furthermore, 1G11 treatment improves CD3+, CD4 + and CD8 + T cell infiltration in tumor tissue.</p><p><strong>Conclusions: </strong>We developed antagonist antibodies targeting LIF/LIFR signaling pathway from a naive human scFv phage library. Antagonist anti-LIF antibody exerts antitumor effects by specifically reducing p-STAT3. Further studies revealed that anti-LIF antibody 1G11 increased immune cell infiltration in tumor tissues.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016323","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
Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients. 治疗前血浆视黄醇结合蛋白 4 水平及其在治疗后的变化可预测银屑病患者的全身治疗反应。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-21 DOI: 10.1186/s12865-024-00647-7
Runting Niu, Zhijia Li, Wanqing Jiang, Qingyan Yang, Xinfei Duan, Lixiao Sun, Zhijie Cheng, Junhui Huang, Lihong Li, Junge Ma, Taiping Hu, Lijuan Zhou, Juan Du, Chang Wang, Feifei Liu

Background: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients.

Methods: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients.

Results: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7.

Conclusion: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

背景:视黄醇结合蛋白4(RBP4)是一种炎症介质,与皮损的形成有关,这表明它参与了银屑病的病理和进展。本研究旨在探讨系统治疗后 RBP4 的变化及其预测银屑病患者治疗反应的能力:这项前瞻性研究共招募了 85 名银屑病患者和 20 名健康受试者。方法:这项前瞻性研究共纳入 85 名银屑病患者和 20 名健康受试者,在银屑病患者的基线和系统治疗后第 12 周(W12)以及健康受试者入组后,用酶联免疫吸附法检测血浆 RBP4。在第12周对银屑病患者的银屑病面积和严重程度指数(PASI)75和PASI 90进行了评估:结果:银屑病患者基线时的 RBP4 比健康受试者高[中位数(四分位间范围):13.39(9.71-22)]:13.39(9.71-22.92)微克/毫升对 9.59(6.57-13.72)微克/毫升](P = 0.003)。在银屑病患者中,有 50 名(58.8%)患者在第 12 个月时 PASI 达到 75,25 名(29.4%)患者在第 12 个月时 PASI 达到 90。与基线水平相比,第 12 个月时的 RBP4 有所下降(P 0.7):血浆 RBP4 在系统治疗后会下降,其基线水平较低,治疗后下降幅度较大,预示着银屑病患者的治疗反应良好。
{"title":"Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients.","authors":"Runting Niu, Zhijia Li, Wanqing Jiang, Qingyan Yang, Xinfei Duan, Lixiao Sun, Zhijie Cheng, Junhui Huang, Lihong Li, Junge Ma, Taiping Hu, Lijuan Zhou, Juan Du, Chang Wang, Feifei Liu","doi":"10.1186/s12865-024-00647-7","DOIUrl":"10.1186/s12865-024-00647-7","url":null,"abstract":"<p><strong>Background: </strong>Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients.</p><p><strong>Methods: </strong>This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients.</p><p><strong>Results: </strong>RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7.</p><p><strong>Conclusion: </strong>Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016324","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
KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalization among HIV-1 unexposed versus exposed uninfected infants in Cameroon 在喀麦隆,KIR2DL1 基因是保护未暴露于 HIV-1 病毒与暴露于未感染病毒的婴儿免于感染相关住院治疗的替代标志物
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-01 DOI: 10.1186/s12865-024-00645-9
Luc-Aimé Kagoué Simeni, Gabriel Loni Ekali, Clauvis Kunkeng Yengo, Rodrigue Kamga Wouambo, Janett Fischer, Oumarou M’rikam A. Bessong, Joseph Fokam, Louis-Marie Yindom, Jules Clément Assob Nguedia
HIV-exposed uninfected infants (HEU) appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cell Immunoglobulin-Like Receptors (KIRs) genes in HEU versus HUU and study their associations with the occurrence of infection-related hospitalization. A cohort study was conducted from May 2019 to April 2020 among HEU and HUU infants, including their follow-up at weeks 6, 12, 24, and 48, in reference pediatric centers in Yaoundé-Cameroon. The infant HIV status and infections were determined. A total of 15 KIR genes were investigated using the sequence-specific primer polymerase chain reaction (PCR-SSP) method. The KIR genes that were significantly associated with HIV-1 status (HEU and HUU) were analyzed for an association with infection-related hospitalizations. This was only possible if, and to the extent that, infection-related hospitalizations varied significantly according to status. Multivariate logistic regression analyses were conducted to determine the association between KIR gene content variants and HIV status, while considering a number of potential confounding factors. Furthermore, the risk was quantified using relative risk, odds ratio, and a 95% confidence interval. The Fisher exact test was employed to compare the frequency of occurrences. A p-value of less than 0.05 was considered statistically significant. In this cohort, a total of 66 infants participated, but only 19 acquired infections requiring hospitalizations (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p = 0.037). At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infection-related hospitalizations was 2.42 (95% CI: 1.028–5.823) for HEU versus HUU with OR 3.59 (1.037–12.448). KIR2DL1 gene was significantly underrepresented in HEU versus HUU (OR = 0.183, 95%CI: 0.053–0.629; p = 0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p < 0.001; aOR = 0.063; 95%CI: 0.017–0.229). Compared to HUU, the vulnerability of HEU is driven by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.
与未感染艾滋病毒的同龄婴儿(HUU)相比,暴露于艾滋病毒的未感染婴儿(HEU)似乎更容易受到感染,这通常归因于从母亲那里获得的被动免疫能力较差。这可能是由于某些可能改变免疫系统的遗传因素造成的。因此,我们试图确定 HEU 与 HUU 中杀伤细胞免疫球蛋白样受体(KIRs)基因的分布情况,并研究它们与感染相关住院的发生率之间的关系。从 2019 年 5 月到 2020 年 4 月,在雅温得-喀麦隆的参考儿科中心对 HEU 和 HUU 婴儿进行了一项队列研究,包括第 6、12、24 和 48 周的随访。确定了婴儿的艾滋病毒感染状况和感染情况。采用序列特异性引物聚合酶链反应(PCR-SSP)方法对总共 15 个 KIR 基因进行了研究。分析了与 HIV-1 感染状况(HEU 和 HUU)明显相关的 KIR 基因与感染相关住院治疗的关系。只有在感染相关住院治疗因感染状况而有显著差异的情况下,才能进行分析。我们进行了多变量逻辑回归分析,以确定 KIR 基因含量变异与 HIV 感染状况之间的关联,同时考虑了一些潜在的混杂因素。此外,还使用相对风险、几率比和 95% 置信区间对风险进行了量化。采用费雪精确检验来比较发生频率。P 值小于 0.05 即为具有统计学意义。在该队列中,共有 66 名婴儿参与,但只有 19 例感染需要住院治疗(14.81%,04/27 HUU;38.46%,15/39 HEU,p = 0.037)。在第 48 周(39 例 HEU 和 27 例 HUU),HEU 与 HUU 的感染相关住院相对风险 (RR) 为 2.42(95% CI:1.028-5.823),OR 为 3.59(1.037-12.448)。KIR2DL1 基因在 HEU 与 HUU 中的代表性明显不足(OR = 0.183,95%CI:0.053-0.629;p = 0.003),KIR2DL1 基因缺失与感染相关住院治疗显著相关(p < 0.001;aOR = 0.063;95%CI:0.017-0.229)。与 HUU 相比,HEU 的易感性是由 KIR2DL1 驱动的,这表明该 KIR 对感染和住院具有保护作用。
{"title":"KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalization among HIV-1 unexposed versus exposed uninfected infants in Cameroon","authors":"Luc-Aimé Kagoué Simeni, Gabriel Loni Ekali, Clauvis Kunkeng Yengo, Rodrigue Kamga Wouambo, Janett Fischer, Oumarou M’rikam A. Bessong, Joseph Fokam, Louis-Marie Yindom, Jules Clément Assob Nguedia","doi":"10.1186/s12865-024-00645-9","DOIUrl":"https://doi.org/10.1186/s12865-024-00645-9","url":null,"abstract":"HIV-exposed uninfected infants (HEU) appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cell Immunoglobulin-Like Receptors (KIRs) genes in HEU versus HUU and study their associations with the occurrence of infection-related hospitalization. A cohort study was conducted from May 2019 to April 2020 among HEU and HUU infants, including their follow-up at weeks 6, 12, 24, and 48, in reference pediatric centers in Yaoundé-Cameroon. The infant HIV status and infections were determined. A total of 15 KIR genes were investigated using the sequence-specific primer polymerase chain reaction (PCR-SSP) method. The KIR genes that were significantly associated with HIV-1 status (HEU and HUU) were analyzed for an association with infection-related hospitalizations. This was only possible if, and to the extent that, infection-related hospitalizations varied significantly according to status. Multivariate logistic regression analyses were conducted to determine the association between KIR gene content variants and HIV status, while considering a number of potential confounding factors. Furthermore, the risk was quantified using relative risk, odds ratio, and a 95% confidence interval. The Fisher exact test was employed to compare the frequency of occurrences. A p-value of less than 0.05 was considered statistically significant. In this cohort, a total of 66 infants participated, but only 19 acquired infections requiring hospitalizations (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p = 0.037). At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infection-related hospitalizations was 2.42 (95% CI: 1.028–5.823) for HEU versus HUU with OR 3.59 (1.037–12.448). KIR2DL1 gene was significantly underrepresented in HEU versus HUU (OR = 0.183, 95%CI: 0.053–0.629; p = 0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p < 0.001; aOR = 0.063; 95%CI: 0.017–0.229). Compared to HUU, the vulnerability of HEU is driven by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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BMC Immunology
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