Evaluation of MX1 Gene Promoter Methylation in Different Severities of COVID-19 Considering Patient Gender

Ghoreshi, Zohreh-al-sadat; Abbasi-Jorjandi, Mojtaba; Asadikaram, Gholamreza; Sharifzak, Mohsen; Rezazadeh-Jabalbarzi, Mitra; Rashidinejad, Hamidreza

doi:10.7754/clin.lab.2022.220104

Cited by 3 publications

(3 citation statements)

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“…It acts as an interferon-stimulated GTPase, crucial for anti-infection responses. 24 MX1 + NK cells show enrichment of pro-inflammatory cytokines and respond to type I interferons, forming a positive feedback loop leading to uncontrolled inflammation in ARDS. Schabmeyer et al found that type I interferons can induce MX1 expression in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…It acts as an interferonstimulated GTPase, crucial for anti-infection responses. 24 MX1 + NK cells show enrichment of pro-inflammatory 25 While type I IFNs are crucial for combating infections, uncontrolled and prolonged type I IFN signaling can be detrimental. 26 Yale Jiang also found extraordinarily high levels of type I IFN along with a sustained IFN gene signature in ARDS patients.…”

Section: Discussionmentioning

confidence: 99%

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Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome

Liu,

Peng,

Liu

et al. 2024

JIR

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Background Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood. Methods A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1 + NK cell infiltration. Results A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46±4.40 vs 11.65±6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1 + NK cells. Flow cytometry analysis showed an elevated percentage of MX1 + NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1 + NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1 + NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand–receptor interaction analysis also revealed extensive interaction between MX1 + NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS. Conclusion MX1 + NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1 + NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome

Liu,

Peng,

Liu

et al. 2024

JIR

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“…The top proteomic contributors in our discriminatory model included interferon-induced GTP-binding protein Mx1 (MX1 or MXA), interferon-stimulated gene 15 (ISG15), Z-DNA-binding protein 1 (ZBP1), and interferon lambda 1 (IFNL1), also referred to as IL-29. Given their responsiveness to IFN signaling, ISG15 and its downstream targets, including MX1 156 , have been implicated as key participants during SARS-CoV-2 infection by using in vitro and in vivo models [157][158][159] as well as samples from COVID-19 patients [160][161][162] . Similarly, the induction of IFNL1 by SARS-CoV-2 infection was previously reported in vitro 163 .…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

et al. 2023

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Background Pregnant women are at greater risk of adverse outcomes, including mortality, as well as obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear. Methods Plasma samples were collected from pregnant women and non-pregnant individuals (male and female) with (n = 72 pregnant, 52 non-pregnant) and without (n = 29 pregnant, 41 non-pregnant) COVID-19. COVID-19 patients were grouped as asymptomatic, mild, moderate, severe, or critically ill according to NIH classifications. Proteomic profiling of 7,288 analytes corresponding to 6,596 unique protein targets was performed using the SOMAmer platform. Results Herein, we profile the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls and show alterations that display a dose-response relationship with disease severity; yet, such proteomic perturbations are dampened during pregnancy. In both pregnant and non-pregnant state, the proteome response induced by COVID-19 shows enrichment of mediators implicated in cytokine storm, endothelial dysfunction, and angiogenesis. Shared and pregnancy-specific proteomic changes are identified: pregnant women display a tailored response that may protect the conceptus from heightened inflammation, while non-pregnant individuals display a stronger response to repel infection. Furthermore, the plasma proteome can accurately identify COVID-19 patients, even when asymptomatic or with mild symptoms. Conclusion This study represents the most comprehensive characterization of the plasma proteome of pregnant and non-pregnant COVID-19 patients. Our findings emphasize the distinct immune modulation between the non-pregnant and pregnant states, providing insight into the pathogenesis of COVID-19 as well as a potential explanation for the more severe outcomes observed in pregnant women.

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Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity

Martinez-Diz,

Morales-Álvarez,

Garcia-Iglesias

et al. 2023

Hum Genomics

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Background The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms. Methods A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria. Results We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10–3), acting as proteases (p = 0.047). Conclusions In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease. Graphical abstract

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Evaluation of MX1 Gene Promoter Methylation in Different Severities of COVID-19 Considering Patient Gender

Cited by 3 publications

References 0 publications

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome

Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity

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