Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Rapid Autopsy and Sample Preparation
2.3. Proteomic Analysis: Olink® Proximity Extension Assay (PEA)
2.4. Pearson’s Correlations Coefficient
2.5. Histology Processing and Immuno-Histochemistry
2.6. Statistical Analysis
3. Results
4. Discussion
Limitations of the Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Abbreviation | Protein Name | Function |
---|---|---|
ADA | Adenosine deaminase | An enzyme converts adenosine to inosine, vital for the differentiation of lymphoid cells while showing enhanced activity in diseases wherein immunity is stimulated [13]. |
BTC | Betacellulin | A member of the EGF family binds to ErbB1 and ErbB4 homodimers, activating the EGFR–PI3K–Akt–Erk pathway to form an inflammatory microenvironment and produce IL-8 [14]. |
CA12 | Carbonic anhydrase 12 | An enzyme catalyzes the hydration of carbon dioxide to bicarbonate and H+ ions, involved in many physiological processes. The similarity between high-altitude pulmonary oedema and COVID-19 suggests the possible role of CA in COVID-19, thus proposing the use of CA inhibitors for COVID-19 treatment [15]. |
CAPG | Macrophage-capping protein | A pro-inflammatory mediator released by macrophage activation subsequently triggers pro-inflammatory cytokine release. The overexpression of CAPG also reveals the ongoing state of inflammatory diseases [16]. |
CD40 | CD40 | CD40 and CD40L are surface receptors, members of the TNF and TNF receptor superfamilies, respectively. Inducing inflammatory and pro-thrombotic responses. CD40 is expressed on monocytes, macrophages, B, T, NK, and dendritic cells. In addition to platelet activation, CD40/CD40L interaction regulates a variety of cellular and molecular processes involved in innate and adaptive immune responses [17]. |
CDCP1 | CUB domain-containing protein 1 | Typically, a key regulator of tumour cell survival and metastasis, affecting immune-mediated diseases; however, CDCP1 is one of the most upregulated genes in SARS-CoV-2-infected children with Kawasaki disease [18]. |
CXCL9 | C-X-C motif chemokine ligand 9 | One of the major chemokines reported being elevated in SARS-CoV infection [19]. |
DPP6 | Dipeptidyl aminopeptidase-like protein 6 | DPP6 overexpression in Purkinje fibres elicits short-coupled extrasystoles triggering idiopathic ventricular fibrillation [20]. |
EDIL3 | EGF-like repeat and discoidin I-like domain-containing protein 3 | A glycoprotein in arterial vessel walls which is overexpressed in Kawasaki disease or after vascular injury; also, it inhibits the recruitment and extravasation of inflammatory cells across the endothelium [21]. |
ENTPD2 | Ectonucleoside triphosphate diphosphohydrolase 2 | Expression of ENTPD2 in the enteric nervous system exacerbates inflammation in inflammatory bowel disease [22]. |
Flt3L | Fms-related tyrosine kinase 3 ligand | Flt3L functions as both a cytokine and a growth factor, increasing the amount of immune cells, especially dendritic cells and lymphocytes [23]. |
IL-6 | Interleukin 6 | High IL-6 has been linked consistently to severe COVID-19 cases [24]. |
IL-8 | Interleukin 8 | A strong biomarker for the severity of COVID-19 and disease prognosis [25]. |
LIF | Leukaemia inhibitory factor | In viral pneumonia, LIF opposes the cytokine storm in the lungs [26]. |
LRP1 | Prolow-density lipoprotein receptor-related protein 1 | A modulator of tissue inflammation and organ repair, e.g., the brain, kidney, lung, vasculature, and AMI [27]. |
OSM | Oncostatin-M | A key regulator of IL-6 and a biomarker for the clinical severity of COVID-19, suggesting the role of bacterial product infection [28]. |
PD-L1 | Programmed cell death 1 ligand 1 | PD-L1 is overexpressed in monocytes, NK cells, and, particularly, basophils and eosinophils in severe COVID-19 patients. The cytokine storm may be led to increased PD-L1 expression, leading to CD8+ T-cell exhaustion. Blockading PD-L1/PD-1 could recover CD8+ T-cell numbers and functionalities [29]. |
PTN | Pleiotrophin | A small cationic protein which is associated with bone development, cancer metastasis, inflammation, neural regeneration, and tissue repair [30]. |
STX8 | Syntaxin-8 | Vesicle trafficking protein is necessary for lytic granule trafficking in cytotoxic T lymphocytes [31]. |
VEGFA | Vascular Endothelial Growth Factor A | Hypoxia upregulates VEGF expression inducing vascular leakiness in SARS-Cov-2-infected lung tissues, resulting in plasma extravasation and pulmonary oedema, later increasing tissue hypoxia in a vicious cycle [32]. |
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Razaghi, A.; Szakos, A.; Alouda, M.; Bozóky, B.; Björnstedt, M.; Szekely, L. Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers. Diagnostics 2022, 12, 2789. https://doi.org/10.3390/diagnostics12112789
Razaghi A, Szakos A, Alouda M, Bozóky B, Björnstedt M, Szekely L. Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers. Diagnostics. 2022; 12(11):2789. https://doi.org/10.3390/diagnostics12112789
Chicago/Turabian StyleRazaghi, Ali, Attila Szakos, Marwa Alouda, Béla Bozóky, Mikael Björnstedt, and Laszlo Szekely. 2022. "Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers" Diagnostics 12, no. 11: 2789. https://doi.org/10.3390/diagnostics12112789
APA StyleRazaghi, A., Szakos, A., Alouda, M., Bozóky, B., Björnstedt, M., & Szekely, L. (2022). Proteomic Analysis of Pleural Effusions from COVID-19 Deceased Patients: Enhanced Inflammatory Markers. Diagnostics, 12(11), 2789. https://doi.org/10.3390/diagnostics12112789