The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker

Abstract

Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1–2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.

Heparin-Binding Protein: A Prognostic Biomarker Associated with Severe or Complicated Community-Acquired Pneumonia in Children

“…Besides, lower airway samples are not feasible for routine disease monitoring. Second, HBP circulates in the blood with a short elimination half-life between 1 and 2 h, 33 suggesting a degree of variability at each point of the disease development. Therefore, dynamic detection may compensate for this deficiency.…”

Dynamic changes in heparin-binding protein as a prognostic biomarker for 30-day mortality in sepsis patients in the intensive care unit

“…Based on our study, we found that the prognostic value of HBP did not increase with time, with baseline HBP and HBPc-48 h having a higher prognostic value than HBPc-24 h. Until recently, the kinetics of HBP in patients with septic shock were not systematically studied. A recent experiment that injected HBP intravenously in rats found that a half-life below 10 min and an elimination half-life of 1–2 h. In the acute inflammation stage, HBP's rapid release and rapid elimination makes serum levels unstable 30 . Recent observations on serial changes in HBP in 12 patients with septic shock corroborated our observations.…”

Progress in the Study of Laboratory Indicators Related to Acute Pancreatitis

“…According to some studies, HBP can also be evaluated as an early biomarker of sepsis severity, and in patients with sepsis, it can predict the progression of organ dysfunction as well as the pathologic course of circulatory failure, respiratory failure, and acute kidney injury. Plasma HBP levels higher than 15 -30 ng/mL are associated with mortality and organ failure in sepsis [25] [26] [27]. Acute pancreatitis, as an inflammatory response, has been found to be associated with HBP and AP in recent years.…”