Evaluating the Timeliness and Specificity of CD69, CD64 and CD25 as Biomarkers of Sepsis in MICE

Published on Apr 1, 2021in Shock2.96
· DOI :10.1097/SHK.0000000000001650
Dinesh G Goswami8
Estimated H-index: 8
(Texas Tech University Health Sciences Center at El Paso),
Luiz F. Garcia1
Estimated H-index: 1
+ 4 AuthorsWendy E Walker3
Estimated H-index: 3
Sources
Abstract
Sepsis occurs when an infection induces a dysregulated immune response, and is most commonly bacterial in origin. This condition requires rapid treatment for successful patient outcomes. However, the current method to confirm infection (blood culture) requires up to 48 h for a positive result and many true cases remain culture-negative. Therefore, new diagnostic tests are urgently needed. Recent clinical studies suggest that CD69, CD64 and CD25 may serve as useful biomarkers of sepsis. In this study, we evaluated the cecal ligation and puncture (CLP) and cecal slurry (CS) mouse models as tools to study these biomarkers in young and aged mice, and elucidate the timeliness and specificity of sepsis diagnosis. Fluorescence-activated cell sorting (FACS) analysis revealed that all three biomarkers were elevated on blood leukocytes during sepsis. CD69 was specifically upregulated during sepsis, while CD64 and CD25 were also transiently upregulated in response to sham surgery. The optimal biomarker, or combination of biomarkers, depended on the timing of detection, mouse age and presence of surgery. CD69 demonstrated an excellent capacity to distinguish sepsis, and in some scenarios the diagnostic performance was enhanced by combining CD69 with CD64. We also analyzed biomarker expression levels on specific cell populations (lymphocytes, monocytes and neutrophils) and determined the cell types that upregulate each biomarker. Elevations in blood biomarkers were also detected via microfluidic analyses; in this case CD64 distinguished septic mice from naive controls. Our results suggest that CD69 and CD64 are valuable biomarkers to rapidly detect sepsis, and that mouse models are useful to study and validate sepsis biomarkers.
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1 CitationsSource
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5 CitationsSource
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9 CitationsSource
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5 CitationsSource
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Neutrophil CD64 is widely described as an accurate biomarker for the diagnosis of infection in patients with septic syndrome. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of neutrophil CD64, comparing it with C-reactive protein (CRP) and procalcitonin (PCT) for the diagnosis of infection in adult patients with septic syndrome, based on sepsis-2 criteria. We searched the PubMed and Embase databases and Google Scholar. Original studies reporting the perfor...
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Abstract Sepsis is a highly prevalent syndrome in the United States. The use of cell surface markers, as an effective tool to diagnosis sepsis, has been widely investigated. However, the study of the combination of multiple biomarkers to achieve higher diagnosis accuracy is rare. This study, the panel combined with CD25, CD64, and CD69 was constructed and better diagnosis ability was observed. Septic patients (n = 40), with the mean age of 61 ± 14, were enrolled in this study, along with healthy...
13 CitationsSource
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16 CitationsSource
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20 CitationsSource
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Cell separations using affinity methods continue to be an enabling science for a wide variety of applications. In this review, we discuss the fundamental aspects of affinity separation, including the competing forces for cell capture and elution, cell-surface interactions, and models for cell adhesion. Factors affecting separation performance such as bond affinity, contact area, and temperature are presented. We also discuss and demonstrate the effects of nonspecific binding on separation perfor...
11 CitationsSource
Cited By3
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#1Julia K. Bohannon (VUMC: Vanderbilt University Medical Center)H-Index: 15
#2Edward R. Sherwood (VUMC: Vanderbilt University Medical Center)H-Index: 50
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#1Erica L. Heipertz (Texas Tech University Health Sciences Center at El Paso)H-Index: 6
#2Wendy E Walker (Texas Tech University Health Sciences Center at El Paso)H-Index: 3
Mice are a suitable animal model for sepsis studies because they recapitulate many aspects of the pathophysiology observed in septic human patients. It is ethically preferable to use mice for research over higher sentient species, when scientifically appropriate. Mice are also advantageous for research due to their small size, modest housing needs, the availability of genetically modified strains, and the broad range of reagents available for scientific assays on this species. Nevertheless, ther...
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#1Dinesh G Goswami (Texas Tech University Health Sciences Center at El Paso)H-Index: 8
#2Wendy E Walker (Texas Tech University Health Sciences Center at El Paso)H-Index: 3
Sepsis arises when an infection induces a dysregulated immune response, resulting in organ damage. New methods are urgently needed to diagnose patients in the early stages of sepsis, and identify patients with a poor disease prognosis. One promising approach is to identify the rapid changes in cell surface antigens (biomarkers) that occur during sepsis, as a consequence of leukocyte mobilization and activation. This chapter describes the method for staining whole blood with fluorescently conjuga...
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