Abstract

Sepsis is a potentially fatal condition caused by infection. It is frequently difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS), often resulting in poor prognoses and the misuse of antibiotics. Hence, highly sensitive and specific biomarkers are needed to differentiate sepsis from SIRS. Urine samples were collected and segregated by group (a sepsis group, a SIRS group, and a healthy control group). iTRAQ was used to identify the differentially expressed proteins among the three groups. The identified proteins were measured by ELISA in urine samples. Finally, all the acquired data were analyzed in SPSS. C-reactive protein, leucine-rich alpha glycoprotein-1 and serum amyloid A (SAA) protein were differentially expressed among the three groups. The adjusted median concentrations of urinary C-reactive protein were 1337.6, 358.7, and 2.4 in the sepsis, SIRS, and healthy control groups, respectively. The urinary leucine-rich alpha glycoprotein-1 levels in these three groups were 1614.4, 644.5, and 13.6, respectively, and the levels of SAA were 6.3, 2.9, and 0.07, respectively. For all three of these measures, the sepsis group had higher levels than the SIRS group (P < 0.001), and the SIRS group had higher levels than the healthy control group. When combined, the three biomarkers had a sensitivity of 0.906 and a specificity of 0.896 in distinguishing sepsis from SIRS. Urinary C-reactive protein, urinary leucine-rich alpha glycoprotein-1 and urinary SAA have diagnostic value in cases of sepsis. This initial study suggests the possibility of improved differential diagnosis between sepsis and systemic inflammatory response syndrome; additional confirmation is necessary to corroborate the findings.

Highlights

  • Sepsis is a potentially fatal condition caused by infection

  • We first verified the existence of C-reactive protein (CRP) in urine, and uCRP/urinary creatinine (u-Cr) was strongly related to s-CRP

  • Human serum amyloid A (SAA) consists of 4 isotypes (SAA1, SAA2, SAA3, SAA4)[46], but the sequence identity of SAA1 and SAA2 is more than 93%, and SAA1 is the main isotype in s­ erum[47]

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Summary

Introduction

Sepsis is a potentially fatal condition caused by infection. It is frequently difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS), often resulting in poor prognoses and the misuse of antibiotics. C-reactive protein, leucine-rich alpha glycoprotein-1 and serum amyloid A (SAA) protein were differentially expressed among the three groups. Urinary C-reactive protein, urinary leucine-rich alpha glycoprotein-1 and urinary SAA have diagnostic value in cases of sepsis. This initial study suggests the possibility of improved differential diagnosis between sepsis and systemic inflammatory response syndrome; additional confirmation is necessary to corroborate the findings. Abbreviations SIRS Systemic inflammatory response syndrome CRP C-reactive protein uCRP Urinary CRP PCT Procalcitonin SAA Serum amyloid A protein uSAA Urinary SAA TREM-1 Triggering receptors expressed on myeloid cells-1 iTRAQ Isobaric tags for relative and absolute quantification ELISA Enzyme linked immunosorbent assay ICU Intensive care unit SOFA Sequential (sepsis-related) organ failure assessment LRG1 Leucine-rich alpha glycoprotein-1 uLRG1 Urinary LRG1 u-Cr Urinary creatinine. We explored the diagnostic value of the combined biomarkers through logistic regression to enhance the diagnostic sensitivity and specificity to sepsis and help clinicians determine the appropriate therapeutic strategy

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