TNFR1, TNFR2, neutrophil gelatinase-associated lipocalin and heparin binding protein in identifying sepsis and predicting outcome in an intensive care cohort

Maria Bergquist,Jonas Tydén,Line Samuelsson,Anders Larsson,Miklos Lipcsey,Joakim Johansson

doi:10.1038/s41598-020-72003-9

Maria Bergquist, Jonas Tydén + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-72003-9

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Abstract

To date no biomarkers can aid diagnosing sepsis with adequate accuracy. We set out to assess the ability of Tumor necrosis factor receptor (TNFR) 1 and 2, Neutrophil gelatinase-associated lipocalin (NGAL) and Heparin binding protein (HBP) to discriminate sepsis from non-infected critically ill patients in a large ICU cohort, and to evaluate their value to predict mortality at 30 days. Adult patients admitted to the ICU with an arterial catheter were included. Clinical data and blood samples were prospectively recorded daily. Diagnoses were set retrospectively. Descriptive statistics and logistic regression models were used. NGAL, TNFR1 and TNFR2 were higher in sepsis patients compared to other diagnoses, as well as in non-survivors compared to survivors. In addition, these biomarkers increased with increasing stages of acute kidney injury. TNFR1 and TNFR2 performed similarly to NGAL and CRP in identifying sepsis patients, but they performed better than CRP in predicting 30-day mortality in this ICU cohort. Thus, TNFR1 and TNFR2 may be particularly useful in identifying high risk sepsis patients and facilitate relevant health care actions in this group of sepsis patients.

Highlights

To date no biomarkers can aid diagnosing sepsis with adequate accuracy
TNFR1 is the main mediator of Tumor necrosis factor (TNF) and ubiquitously expressed while TNFR2 is mainly expressed on immune cells7
Neutrophil gelatinase-associated lipocalin (NGAL) is a critical component of innate immunity to bacterial infection14, released by neutrophils and macrophages as well as renal tubular cells15, explaining why it is best known as a marker of acute kidney injury (AKI)15

Summary

Introduction

To date no biomarkers can aid diagnosing sepsis with adequate accuracy. We set out to assess the ability of Tumor necrosis factor receptor (TNFR) 1 and 2, Neutrophil gelatinase-associated lipocalin (NGAL) and Heparin binding protein (HBP) to discriminate sepsis from non-infected critically ill patients in a large ICU cohort, and to evaluate their value to predict mortality at 30 days. Tumor necrosis factor (TNF) is a potent pro-inflammatory cytokine with a pivotal signaling role in the host defense against infection and injury, as well as controlling the survival of target cells6 It exerts immunological effects through two cell surface receptors, TNFR1 (p55TNFR) and TNFR2 (p75TNFR). An increased concentration of circulating TNFRs in combination with a decreased concentration of available cell surface receptor proteins, could result in a significant attenuation of the pro-inflammatory TNF activity and bioavailability Supporting this hypothesis, defective shedding has been observed to cause innate immune hyperresponsiveness and in vivo toxicity from TNF and LPS13. NGAL concentrations have been associated with inflammatory response, endothelial activation and clinical outcome in sepsis18–20 It has not been confirmed if increased concentrations of plasma NGAL could be used as an early biomarker to identify patients with sepsis from patients with inflammation rising from other causes than infection

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