COVID-19 Diagnostics: Study Indicates That Acetylated K676 TGFBIp Can Be Used As A Severity Diagnostic Blood Biomarker For SARS-CoV-2 Pneumonia
: Korean researchers in a new study found raised levels of transforming growth factor beta-induced protein (TGFBIp) in blood sampled from roughly 100 people hospitalized for COVID-19, and further found that elevated levels of both the normal and acetylated forms of TGFBIp correlated with the severity of disease symptoms in these patients.
The researchers suggest that acetylated K676 TGFBIp can be used as a severity diagnostic blood biomarker for SARS-CoV-2 pneumonia.
The research findings are published in the Journal: Science Advances. https://advances.sciencemag.org/content/early/2020/07/24/sciadv.abc1564.1.abstract
Transforming growth factor-β–induced protein (TGFBIp)/βig-h3 is a 68-kDa extracellular matrix protein that is functionally associated with the adhesion, migration, proliferation, and differentiation of various cells. The presence of TGFBIp in platelets also shows the role of this protein in the regulation of platelet functions. Upon activation, platelet TGFBIp was released and associated with the platelets. TGFBIp mediates not only the adhesion and spread of platelets but also activates them, resulting in phosphatidylserine exposure, α-granule secretion, and increased integrin affinity. Hence it also promotes thrombogenesis. https://ashpublications.org/blood/article/114/25/5206/26522/Transforming-growth-factor-induced-protein-TGFBIp
Although more work will be required to determine whether heightened levels of acetylated TGFBIp can serve as an exclusive, specific, and reliable diagnostic indicator for the severity of COVID-19, the Korean research also suggests that TGFBIp could be a viable therapeutic target to treat severe inflammation - including deadly "cytokine storms" - in patients suffering from severe cases of the disease.
While a lot of work has been done to characterize the immune responses of patients with COVID-19, the inflammatory markers and cytokines known to be induced by SARS-CoV-2 infection are often short-lived.
Dr Hee Ho Park and colleagues set out to investigate whether increased levels of both the normal and acetylated forms of TGFBIp, a more stable molecule known to activate the immune-regulating transcription factor NF-κB, might serve as a more lasting signal of SARS-CoV-2 infection.
The study team analyzed blood samples from healthy controls and two cohorts of COVID-19 patients: those admitted to a hospital for treatment with relatively mild symptoms, and those who required ICU care to treat acute respiratory distress syndrome (ARDS) and/or sepsis.
When compared with the healthy controls, both patient cohorts exhibited elevated levels of TGFBIp, as well as higher levels of acetylated TGFBIp, with the ICU patients exhibiting even greater levels of both protein forms.
Interestingly upon treating immune cells taken from these patients with antibodies that neutralize TGFBIp, the researchers also observed a decrease in the production of inflammatory cytokines.
Though further work will be required to validate these results and assess the safety of the neutralizing antibodies, the finding nonetheless suggests that TGFBIp could be targeted to help treat severe inflammation in COVID-19 patients.
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