DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

Linlin Gao ,Hairong Zhang,Sunghee Kim,Jingrong Chen,Junying Chen,Wei Chen,Paul Okunieff,Ruilong Lan,Lurong Zhang,Zhenhuan Zhang,Zeng Wang,Qishui Ou,Bing Wu,Mei Zhang,Jianhua Lin,Hengshan Zhang,Long Chen,Ruiqing Chen,Deping Han,Bin Yang,Jian‐Li Lin ,Liya Fu ,Yu Lin

doi:10.18632/oncotarget.23736

Abstract

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis (n = 134), SIRS (n = 60) and normal adults (n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1–2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis (rs = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1–2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

Highlights

Sepsis, the most common complication of the endstage of many diseases, such as cancer, cardiovascular dysfunction, trauma, shock, infections, aging, etc. has a mortality rate up to ~30% [1]
The trauma, stroke, surgical operation on brain and chest were the main causes of systemic inflammation response syndrome (SIRS), while some SIRS transition into sepsis, some of sepsis were due to chronic diseases of lung, liver, heart and kidney
All 134 sepsis patients were followed for decoy receptor 3 (DcR3), PCT, C reaction protein (CRP), and interleukin 6 (IL-6) levels during the whole course of hospitalization

Summary

Introduction

The most common complication of the endstage of many diseases, such as cancer (especially after chemotherapy exhausting the defense immune system), cardiovascular dysfunction, trauma, shock, infections, aging, etc. has a mortality rate up to ~30% [1]. Because each hour that treatment is delayed increases mortality rates by 5–10%, early diagnosis and monitoring of treatment effectiveness are the keys to saving patients’ lives [2,3]. CRP and IL-6 are unspecific pro-inflammatory molecules that increase in many acute diseases, including infection [9,10,11,12,13]. Molecule with an opposite effect, such as DcR3, (a soluble decoy receptor 3 of the TNFR family with a binding domain without a signal transduction domain, 18), is upregulated to block the function of three pro-apoptotic molecules, such as Fas L [18], LIGHT [19] and TL1A [20], and serve as modulators or protective factors [21]

Methods

Results

Conclusion