Significance of diagnostic and therapeutic potential of serum endothelial and inflammatory biomarkers in defining disease severity of dengue infected patients.

IF 5.5 3区医学 Q1 IMMUNOLOGY Medical Microbiology and Immunology Pub Date : 2024-12-14 DOI:10.1007/s00430-024-00810-2

Priyanka Ghosh, Bibhuti Saha, Krishnasamy Kaveri, Anusri Tripathi

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Abstract

Dengue virus (DENV) mediated disease severity leads to fatality among infected patients. Immune sentinels recognize DENV thereby secreting inflammatory mediators, endothelial biomarkers and anticoagulation factors. Absence of any diagnostic biomarkers for early identification of severe dengue (SD) patients has hindered disease management. Present study is aimed to evaluate diagnostic potential of these biomarkers along with their therapeutic targets for disease severity. Dengue infection was screened among 214 symptomatic patients and 25 healthy individuals by qRT-PCR, NS1-antigen, anti-dengue-IgM, anti-dengue-IgG ELISA and categorized them according to WHO-classification, 2009. Dengue viral-load and serotypes were determined by qRT-PCR. Serum-protein concentrations of inflammatory mediators (MIF, PAF, MMP2, MMP9, MCP1, RANTES, STNFRI, ST2, EOTAXIN), endothelial biomarkers (SDC1, VEGF, ANGPT2), anticoagulation factors (sTM, vWF, TF, PAI) were determined by sandwich ELISA. Statistical, PPI-network, hub-proteins, drug prediction analysis were performed by GraphPad-Prism⁹, STRING, Cytoscape-cytoHubba, DrugBank online, TTD, respectively. Among 81 dengue infected patients, significantly higher levels of MIF, PAF, sTNFRI, MMP9, VEGF, ANGPT2, MMP2, RANTES, SDC1 were detected among SD patients compared to non-severe ones, with excellent and good diagnostic potential of first (> 77.11, > 57.57 ng/ml, > 3226 pg/ml) and next three (> 105.3 ng/ml, > 12,380, > 8284 pg/ml) biomarkers, respectively. Serum MIF, PAF, MMP9, sTNFRI levels were significantly higher among hospitalized (p-value: 0.0081-0.0499), high-viral-load (p-value: 0.0266-0.0466) and DENV-2, 4 (p-value: < 0.0001-0.0298) infected patients. PPI-network analysed MMP9, PAI, vWF, ANGPT2, sTM, sTNFRI, MIF as hub-proteins targeted by FDA-approved/experimental drugs. This study recognized serum-biomarkers: MIF, PAF, sTNFRI, MMP9, VEGF, ANGPT2 to have significant diagnostic potential for identification of SD cases.

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血清内皮和炎症生物标志物在确定登革热感染者病情严重程度方面的诊断和治疗潜力。

登革热病毒（DENV）介导的疾病严重程度导致感染者死亡。免疫哨兵会识别登革热病毒，从而分泌炎症介质、内皮生物标志物和抗凝因子。由于缺乏早期识别重症登革热（SD）患者的诊断生物标志物，阻碍了疾病的治疗。本研究旨在评估这些生物标志物的诊断潜力及其对疾病严重程度的治疗目标。研究人员通过 qRT-PCR、NS1-抗原、抗登革热 IgM、抗登革热 IgG ELISA 对 214 名有症状的登革热患者和 25 名健康人进行了登革热感染筛查，并根据 2009 年世界卫生组织的分类对他们进行了分类。通过 qRT-PCR 测定登革热病毒载量和血清型。通过夹心酶联免疫吸附测定炎症介质（MIF、PAF、MMP2、MMP9、MCP1、RANTES、STNFRI、ST2、EOTAXIN）、内皮生物标志物（SDC1、VEGF、ANGPT2）、抗凝因子（sTM、vWF、TF、PAI）的血清蛋白浓度。采用 GraphPad-Prism9、STRING、Cytoscape-cytoHubba、DrugBank online 和 TTD 分别进行了统计分析、PPI-网络分析、枢纽蛋白分析和药物预测分析。在81名登革热感染者中，与非重症患者相比，重症患者的MIF、PAF、sTNFRI、MMP9、VEGF、ANGPT2、MMP2、RANTES、SDC1水平明显较高，其中第一个（> 77.11、> 57.57 ng/ml、> 3226 pg/ml）和后三个（> 105.3 ng/ml、> 12380、> 8284 pg/ml）生物标志物的诊断潜力分别为极佳和良好。血清 MIF、PAF、MMP9 和 sTNFRI 水平在住院患者（p 值：0.0081-0.0499）、高病毒载量患者（p 值：0.0266-0.0466）和 DENV-2、4 型患者（p 值：0.0266-0.0466）中明显较高：

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来源期刊

Medical Microbiology and Immunology 医学-免疫学

CiteScore

10.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.