When Cultures Fail: Postmortem Decoy Receptor 3 (DcR3) as a Marker of Antemortem Sepsis

Abstract

Introduction: Decoy receptor 3 (DcR3) has shown utility as a reliable surrogate marker. Levels of DcR3 in the serum increase and remain elevated in several disease states including cancer and sepsis. In inflammatory conditions, DcR3 is upregulated in inflammatory cells to suppress exponential immune propagation. The use of DcR3 as an indication of sepsis has been documented in the antemortem setting, but its use in the postmortem setting is unknown. The purpose of this study is to evaluate postmortem DcR3 as a marker of antemortem sepsis. Methods: A retrospective investigation was performed to identify patients whose primary cause of death fell into one of four cohorts (control, cancer, culture-positive sepsis, and suspected culture-negative sepsis). Serum was obtained and tested by a commercially available enzyme-linked immunosorbent assay to quantify DcR3 levels. Results: Twenty-five of 47 samples contained detectable levels of DcR3 (average 0.75 ± 0.3 ng/mL). Comparing culture-positive sepsis to the control cohort at a cutoff value of 0.26 ng/mL, DcR3 positivity showed a sensitivity of 64% and a specificity of 73%. Compared to each other, patients with cancer had similar values to those with culture-positive sepsis (P = .90). Time of specimen collection had a negative role in detection and quantification (P = .038). Discussion: Several studies have shown DcR3 may be a viable antemortem biomarker of sepsis, but its use in postmortem sepsis testing has not been adequately investigated. This study shows that in postmortem testing, DcR3 shows less sensitivity and specificity with a relatively short window for proper testing.

Sudden Death: A Practical Autopsy Approach to Unexplained Mediastinitis Due to Fatal Untreated Neck Infections—A Systematic Review

“…Nevertheless, we discourage reliance on bacterial cultures in such cases. It is more reliable to determine the anatomical relationships via macroscopical examination since it is difficult to obtain noncontaminated results in post-mortem swabs [ 42 ].…”

Inhibitory mechanisms of decoy receptor 3 in cecal ligation and puncture-induced sepsis

“…Attenuation of inflammation and apoptosis has become a critical component in treating sepsis ( 26 , 27 ). DcR3 can competitively bind to FasL, LIGHT, and TL1A through its decoy function, thereby blocking the original biological activity of the ligands and the downstream signal transduction, which ultimately leads to anti-inflammatory effects ( 14 , 28 ). DcR3.Fc inhibits the TL1A-induced activation of NF-κB ( 29 ), and DcR3 can reduce the expression levels of inflammatory markers by neutralizing FasL.…”

“…A moderate elevation of DcR3 can be observed in various malignancies, inflammatory conditions, and autoimmune disorders ( 13 ). Additionally, bacterial antigens, such as LPS and lipoteichoic acid, selectively induce DcR3 ( 14 ).…”

Research Progress of DcR3 in the Diagnosis and Treatment of Sepsis

“…Furthermore, the higher the APACHE II score, the higher the DcR3 level in patients with sepsis, suggesting that the DcR3 level is positively correlated with the severity of sepsis in patients [ 8 ]. Moreover, DcR3 is universally present in different species and, therefore, can be used as a sepsis biomarker [ 8 , 28 , 97 , 98 ]. DcR3 can also differentiate sepsis from SIRS, a systemic inflammatory disease caused by non-infectious factors that is primarily treated with steroids.…”