sCD14-ST Series 1 - Applications in Special Clinical Scenarios

2022-11-21

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Infection is common in people of all ages and around the globe. However, the signs of infection are not always noticeable and differentiating them accurately can be a challenge.

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To address the rising burden of infectious disease on hospitals, Mindray has developed sCD14-ST, a biomarker that is sensitive and accurate for the detection of infection.

 

sCD14-ST, a soluble subtype of CD14, is a glycoprotein fragment derived from monocytes and macrophages. It is a biomarker indicating the activation of innate immune cell response to an invading pathogen [1-3].

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As a result of such response, CD14 will be expressed on the surface of various immune cells. CD14 then binds to the LPS/LBP complex and activates TLR4. Then, it initiates innate immune response to infectious agents. After that, sCD14 is cleaved by cathepsin D and other proteases. The N-terminal fragments of CD14 are released and sCD14-ST is formed [1-3].

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The physiological mechanism of sCD14-ST [1-3]

Compared to PCT induced by cytokines after bacterial phagocytosis, sCD14-ST is a more direct infectious biomarker, which is mediated by pathogens [1-2].

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Pathological studies and clinical trials have revealed that sCD14-ST is important for the clinical management of infectious diseases or related conditions, such as neonatal sepsis, prosthetic joint infection (PJI), febrile neutropenia (FN), sepsis, and early infection in trauma.

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sCD14-ST shows high specificity and sensitivity for some special scenarios such as prosthetic joint infection (PJI) and febrile neutropenia (FN) for which there is always a lack of ideal diagnostic methods.


Prosthetic joint infection (PJI) is a tremendous burden for individual patients as well as the global health care industry [4]. The nature of implant-related infections is complex. Currently, there is no definitive test for PJI and its diagnosis remains challenging despite recent developments [5]. While a small minority of joint arthroplasties will become infected, appropriate recognition and management are critical to preserve or restore adequate function and prevent excess morbidity [4].

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sCD14-ST is found to be a potential inflammation biomarker for PJI diagnosis and prognosis. Research has revealed that its level is significantly higher in PJI patients than controls. In PJI patients after surgery, the sCD14-ST level is significantly higher, which means a longer recovery time; in non-infected patients, however, the sCD14-ST level is significantly lower [6].

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Febrile neutropenia (FN) is the most common life-threatening complication of cancer therapy. It is defined as a single oral temperature measurement of >101°F (>38.3°C) or a temperature of ≥100.4°F (≥38.0°C) sustained over 1 hour, with an absolute neutrophil count (ANC) of <500 cells/microliter, or an ANC that is expected to decrease to <500 cells/microliter over the next 48 hours [7].

 

Traditional methods such as liver function tests and blood cultures for bacteria can be used to support the first investigation of FN, but they all have some drawbacks.

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From researches, sCD14-ST is considered to be an early diagnostic marker of FN in hematologic malignancy patients. According to studies on FN cases, the sCD14-ST level elevates one day prior to CRP. Plasma sCD14-ST level is a reliable marker of FN even in extremely low WBC counts. Besides, evaluation of sCD14-ST level increase helps with the early diagnosis of FN in both myeloid and lymphoid disorders. Close monitoring of this molecule could prevent infection-associated deaths in hematologic malignancy cases [8].

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Fig. Plasma sCD14-ST levels in representative case

In such special scenarios, sCD14-ST can be used as a novel biomarker for disease management.

 

In series 2, we will introduce more clinical applications of sCD14-ST in other commonly seen diseases such as sepsis and bacterial infection.


If you have interest in this inflammation biomarker, please register to watch Mindray IPS (IL-6, PCT and sCD14-ST) online launch event on 1st December, 2022: https://www.mindray.com/en/events/webinar-on-il-6-scd14-st

References

[1] Bas S, Gauthier B R, Spenato U, et al. CD14 is an acute-phase protein[J]. J Immunol, 2004, 172(7): 4470-9.
[2] Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34(5): 637-50
[3] "Presepsin (sCD14-ST), an innate immune response marker in sepsis." Clinica Chimica Acta 450(2015):97-103.
[4] Aaron J. Tandea, and Robin Patelcorresponding authora,b, Prosthetic Joint Infection, Clin Microbiol Rev. 2014 Apr; 27(2): 302–345. doi: 10.1128/CMR.00111-13
[5] Seung-Ju Kim, MD, PhDcorresponding author and Yun Jae Cho, MD, Current Guideline for Diagnosis of Periprosthetic Joint Infection: A Review Article. Hip Pelvis.2021 Mar; 33(1): 11–17. 2021 Mar 2. doi: 10.5371/hp.2021.33.1.11
[6] Monica Gioia Marazzi, et al. Presepsin: A potential biomarker of PJI.A comparative analysis with known and new infection biomarkers. DOI: 10.1177/0394632017749356
[7] https://bestpractice.bmj.com/topics/en-us/950
[8] Koizumi et al. Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients.BMC Infectious Diseases (2017) 17:27