Acetylated K676 TGFBIp as a severity diagnostic blood biomarker for SARS-CoV-2 pneumonia

Sci Adv. 2020 Jul 31;6(31):eabc1564. doi: 10.1126/sciadv.abc1564. Print 2020 Jul.

Abstract

The outbreak of the highly contagious and deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), has posed a serious threat to public health across the globe, calling for the development of effective diagnostic markers and therapeutics. Here, we report a highly reliable severity diagnostic biomarker, acetylated 676th lysine transforming growth factor-beta-induced protein (TGFBIp K676Ac). TGFBIp K676Ac was consistently elevated in the blood of patients with SARS-CoV-2 pneumonia (n = 113), especially in patients in the intensive care unit (ICU) compared to non-ICU patients. Patients' blood samples showed increased cytokines and lymphopenia, which are exemplary indicators of SARS-CoV-2 pneumonia. Treatment with TGFBIp neutralizing antibodies suppressed the cytokine storm. The increased level of TGFBIp K676Ac in ICU patients suggests the promise of this protein as a reliable severity diagnostic biomarker for severe SARS-CoV-2 disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Antibodies, Neutralizing / pharmacology
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity*
  • Biomarkers / blood
  • COVID-19
  • Case-Control Studies
  • Coronavirus Infections / blood
  • Coronavirus Infections / diagnosis*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology
  • Cytokine Release Syndrome / blood
  • Cytokine Release Syndrome / diagnosis*
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / pathology
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / immunology*
  • Gene Expression
  • Humans
  • Intensive Care Units
  • Leukocyte Count
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / pathology
  • Leukocytes, Mononuclear / virology
  • Lung / blood supply
  • Lung / drug effects
  • Lung / pathology
  • Lung / virology
  • Lysine / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / diagnosis*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology
  • Primary Cell Culture
  • Prognosis
  • Protein Processing, Post-Translational*
  • Respiratory Insufficiency / blood
  • Respiratory Insufficiency / diagnosis*
  • Respiratory Insufficiency / immunology
  • Respiratory Insufficiency / pathology
  • SARS-CoV-2
  • Severity of Illness Index
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*

Substances

  • Antibodies, Neutralizing
  • Biomarkers
  • Extracellular Matrix Proteins
  • NF-kappa B
  • Transforming Growth Factor beta
  • betaIG-H3 protein
  • Lysine