Soluble CD14 Subtype in Peripheral Blood Is a Biomarker for Early Diagnosis of Sepsis

Wuqiong Zhou MD; Heping Rao PhD; Qiuming Ding MD; Xiang Lou MMS; Jianjiang Shen MPH; Bin Ye MD; Caixia Xiang PhD


Lab Med. 2020;51(6):614-619. 

In This Article

Abstract and Introduction


Objective: To study the value of serum soluble CD14 subtype (sCD14-ST) in early diagnosis of sepsis.

Methods: Seventy-two patients were diagnosed with systemic inflammatory response syndrome, sepsis, or septic shock. Peripheral blood was collected at 0, 12, 24, and 48 hours after admission to the hospital. Levels of sCD14-ST, procalcitonin (PCT), hypersensitive C-reactive protein (CRP), and white blood cells (WBC) were determined.

Results: Levels of sCD14-ST in the patients with septic shock were higher than those in the other patients (P < .01) and peaked at 48 h. PCT and CRP levels were similar in the patients at admission but increased by 5 times to 10 times in the next 48 h, especially in the patients with septic shock. WBC levels remained high and did not change dramatically. Receiver operating characteristic analysis revealed that the area under the curve, sensitivity, and specificity values of sCD14-ST to diagnose sepsis were much higher than those of the other markers.

Conclusion: Compared with PCT, CRP, and WBC, sCD14-ST is a better biomarker for the early diagnosis of sepsis.


Sepsis is a systemic inflammatory response caused by local infection, which develops rapidly and can lead to death with multiple tissue damage and multiple organ failure.[1,2] The mortality rate of sepsis can be up to 40%, and the incidence of sepsis has increased by 1.5% per year.[3,4] For every 1-hour delay in effective antibiotic treatment during the first 6 hours of sepsis, the death rate of patients increases by about 7.6%,[5] and antibiotic treatment after 24 hours of the onset of sepsis is generally not effective.[6] A 1991 consensus conference developed the initial definition of sepsis, which included an excessive focus on inflammation and on the inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria.[7] The Third International Consensus Conference defined sepsis as "life-threatening organ dysfunction caused by a dysregulated host response to infection." [8]

Early diagnosis of sepsis is very important to reduce mortality. Currently, procalcitonin (PCT) is used as a biomarker in the clinical diagnosis of sepsis. The level of PCT increases significantly in sepsis, especially in patients with positive blood culture or septic shock.[9] However, false-negative results might occur in some patients with sepsis, especially in the early stage when the PCT level is low.[10,11] Furthermore, PCT can be nonspecifically elevated in certain clinical contexts, such as some end-organ dysfunctions, postsurgical anastomotic leaks, acute kidney injury, cardiogenic shock, anaphylaxis, and complications after intracerebral hemorrhage.[12,13] Blood culture is the "gold standard" for the diagnosis of sepsis; however, it usually takes 48 to 72 hours, and its sensitivity is low.[14] In addition, C-reactive protein (CRP) and white blood cells (WBC) are commonly used markers to screen for infection; however, in the diagnosis of sepsis, their specificity and reliability are low.[15] Moreover, besides infection, high levels of CRP and WBC are found in noninfectious stress, trauma, aseptic inflammation, and tumors.[15]

CD14 is the receptor for the lipopolysaccharide (LPS)–LPS binding protein complex and exists in 2 forms, the membrane bound type (mCD14) and the soluble type (sCD14).[16] sCD14 exists in plasma and originates from secreted mCD14.[16–18] CD14 mediates the cell response to LPS and activates the Toll-like receptor 4-specific proinflammatory signaling cascade.[19] CD14 is also involved in the recognition of a wide variety of other bacterial products, such as peptidoglycans of gram-positive bacteria, and it reaches high levels in the early stage of sepsis.[17–19] During systemic inflammation or bacterial infections, circulating plasma proteases cleave the soluble fraction of CD14 to generate a truncated form named sCD14 subtype (sCD14-ST), also known as presepsin.[20] The release of sCD14-ST is a very fast response. Chenevier-Gobeaux et al[21] constructed an in vitro experimental model of sepsis by challenging THP-1 cells, a human monocytic cell line, with LPS, and found that sCD14 could be detected at 1 h and peaked at 3 h after LPS exposure. To observe the changes in sCD14-ST in patients with sepsis and explore its potential value in the early diagnosis of sepsis, we detected the serum sCD14-ST levels in patients with SIRS or sepsis at 0, 12, 24, and 48 hours after admission to the intensive care unit (ICU) and compared its diagnostic value for sepsis with that of WBC, CRP, and PCT using receiver operating characteristic (ROC) analysis. We found sCD14-ST levels increased in the very early stage, especially in patients with septic shock. The sensitivity and specificity of sCD14-ST to diagnose sepsis were better than those of PCT, CRP, and WBC.