| Autor: |
Sorrells MG; Cytovale Inc., San Francisco, CA 94134, USA., Seo Y; Departments of Medicine and Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Magnen M; Departments of Medicine and Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Broussard B; Department of Biological Sciences, Nicholls State University, Thibodaux, LA 70310, USA., Sheybani R; Cytovale Inc., San Francisco, CA 94134, USA., Shah AM; Cytovale Inc., San Francisco, CA 94134, USA., O'Neal HR; LSU Health Sciences Center/Our Lady of the Lake Regional Medical Center, Baton Rouge, LA 70808, USA., Tse HTK Jr; Cytovale Inc., San Francisco, CA 94134, USA., Looney MR; Departments of Medicine and Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Di Carlo D; Departments of Bioengineering and Mechanical and Aerospace Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA. |
| Abstrakt: |
Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200: p < 10 -10 ; 0 and 400: p < 10 -10 ). Linear correlation was observed between the ISI and quantities of NE DNA and Cit-H3 DNA in patient samples. Together these experiments demonstrate that the IntelliSep test is associated with the biological processes of leukocyte activation and NETosis and may indicate changes consistent with sepsis. |
