CXCL10/IP10 as a Biomarker Linking Multisystem Inflammatory Syndrome and Left Ventricular Dysfunction in Children with SARS-CoV-2

Başar, Eviç Zeynep; Sönmez, Hafize Emine; Uzuner, Hüseyin; Karadenizli, Aynur; Güngör, Hüseyin Salih; Akgün, Gökmen; Yetimakman, Ayşe Filiz; Öncel, Selim; Babaoğlu, Kadir

doi:10.3390/jcm11051416

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…IP-10 has been suggested as a potential biomarker to predict left ventricular dysfunction in MIS-C patients. 20 Our MIS-A patients, all with cardiovascular manifestations, demonstrated elevated IP-10 levels. Patient 3's echocardiogram was performed 2 weeks after admission and administration of corticosteroids and IVIG, and it is possible that his cardiac function had improved by the time his cardiac imaging was performed.…”

Section: Discussionmentioning

confidence: 64%

Immune and coagulation profiles in 3 adults with multisystem inflammatory syndrome

Yap

Leung

Howe

et al. 2023

Ann Acad Med Singap

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Introduction: There is a paucity of information on the cytokine, complement, endothelial activation, and coagulation profiles of multisystem inflammatory syndrome in adults (MIS-A), a rare but serious complication following recovery from SARS-CoV-2 infection. We aim to examine the immune biomarker and coagulation profiles in association with the clinical presentation and course of MIS-A. Method: The clinical features of MIS-A patients admitted to our tertiary hospital were documented. Their levels of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-18, interferon-α (IFN-α), IFN-γ, interferon gamma-induced protein 10 (IP-10), tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, complement activation product (complement 5a [C5a]), and endothelial biomarker intercellular adhesion molecule-1 (ICAM-1) levels were assayed. The haemostatic profile was assessed with standard coagulation testing and thromboelastography. Results: Three male patients were diagnosed with MIS-A at our centre from January to June 2022 with a median age of 55 years. All had tested positive for SARS-CoV-2 12–62 days prior to MIS-A presentation, with gastrointestinal and cardiovascular systems as the most commonly involved. Levels of IL-6, IL-10, IL-18, IP-10 and MCP-1 were raised whereas IL-1β, IFN-α, IFN-γ, IL-17 and TNF-α remained normal. Markedly elevated levels of C-reactive protein (CRP), ferritin and ICAM-1 were present in all. C5a was elevated in 2 patients. A hypercoagulable state was demonstrated by raised levels of D-dimer, factor VIII, von Willebrand factor antigen, and ristocetin cofactor with corresponding raised parameters in thromboelastography in the 2 patients who had their coagulation profile assessed. Conclusion: MIS-A patients demonstrate activation of pro-inflammatory cytokines, endotheliopathy, complement hyperactivation and hypercoagulability. Keywords: COVID-19, cytokines, hypercoagulability, hyperinflammatory syndrome

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Section: Discussionmentioning

confidence: 64%

Immune and coagulation profiles in 3 adults with multisystem inflammatory syndrome

Yap

Leung

Howe

et al. 2023

Ann Acad Med Singap

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“…Also, it’s reported that the deletion of TNFSF14 may correlate with a decrease in IFN-γ-producing CD4 + T cells, which mediated immunopathogenesis of ocular Herpes simplex virus 1 (HSV-1) infection as the Herpesvirus entry mediator (HVEM) binding partner [ 27 ]. Besides, CXCL10 and CXCL11 bonded the receptor CXCR3 and exerted a potent chemotactic effect on activated T lymphocytes [ 28 – 30 ]. Additionally, CH25H was induced in response to ZIKV infection, and its enzymatic product 25HC was a critical mediator of host protection against ZIKV, which had also been characterized as a broad-spectrum antiviral drug that inhibited viruses including ZIKV [ 31 – 33 ].…”

Section: Resultsmentioning

confidence: 99%

Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis

et al. 2022

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Background Recently, Zika virus (ZIKV) re-emerged in India and was potentially associated with microcephaly. However, the molecular mechanisms underlying ZIKV pathogenesis remain to be explored. Results Herein, we performed a comprehensive RNA-sequencing analysis on ZIKV-infected JEG-3, U-251 MG, and HK-2 cells versus corresponding uninfected controls. Combined with a series of functional analyses, including gene annotation, pathway enrichment, and protein–protein interaction (PPI) network analysis, we defined the molecular characteristics induced by ZIKV infection in different tissues and invasion time points. Data showed that ZIKV infection and replication in each susceptible organ commonly stimulated interferon production and down-regulated metabolic-related processes. Also, tissue-specific immune responses or biological processes (BPs) were induced after ZIKV infection, including GnRH signaling pathway in JEG-3 cells, MAPK signaling pathway in U-251 MG cells, and PPAR signaling pathway in HK-2 cells. Of note, ZIKV infection induced delayed antiviral interferon responses in the placenta-derived cell lines, which potentially explains the molecular mechanism by which ZIKV replicates rapidly in the placenta and subsequential vertical transmission occurs. Conclusions Together, these data may provide a systemic insight into the pathogenesis of ZIKV infection in distinct human tissue-derived cell lines, which is likely to help develop prophylactic and therapeutic strategies against ZIKV infection.

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“…But also, transforming, and vascular endothelial cellular growth factors (TGF-β/VEGF)) along-side specific matrix metalloproteinases (MMP2, MMP3, MMP9) that represent tissue re-modelling proteins with specific chemotactic factors required to direct leukocyte chemotaxis between GC and throughout the body that include CXCL10 (IP-10), CCL2 (MCP-1), CCL3 (MIP1-α, and CCL11 [51][52][53][54][55]. However, in Middle East Respiratory Syndrome (MERS) IL-1β, IL-8, and IL-6 were highlighted whereas in SARS-CoV-2 CXCL10 does appear to be a key pleiotropic chemokine that has since been clarified in SARS-CoV-2 utilizing CXCR3 expressed on Mϕ, T cells, dendritic cells and both NK and B cells [56][57][58].…”

Section: Coagulopathy and Cytokinesmentioning

confidence: 99%

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

Brown¹

2022

Preprint

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The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

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CXCL10/IP10 as a Biomarker Linking Multisystem Inflammatory Syndrome and Left Ventricular Dysfunction in Children with SARS-CoV-2

Cited by 8 publications

References 31 publications

Immune and coagulation profiles in 3 adults with multisystem inflammatory syndrome

Immune and coagulation profiles in 3 adults with multisystem inflammatory syndrome

Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

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