• Elgass, Kirstin
• Ong, Yih Rue
• Avalos, Bárbara De La Peña
• Jacques, Angela
• Cheng, Qiang
• Li, Anqi
• Lipman, Jeffery
• Denny, Kerina
• Walsham, James
• Kruger, Peter
• Meyer, Jason
• Saylor, Emma

Abstract

<jats:title>Abstract</jats:title><jats:p><jats:bold>Background:</jats:bold> The lack of rapid and accurate diagnostic tools to distinguish infectious (known as sepsis) and non-infectious causes of inflammation in patients with systemic inflammation remains a significantly unmet clinic need, particularly in the intensive care unit (ICU). As a hallmark of inflammation, circulating leukocytes must be activated and undergo a cascade of interactions with blood vessel endothelium before transmigrating into surrounding tissues, a process called leukocyte recruitment. Given the divergent disease aetiologies, it was hypothesised that the ability of circulating leukocytes to interact with endothelial cells and cause inflammation may differ when responding to infectious and non-infectious inflammatory stimuli, providing potential markers to differentiate these two diseases. <jats:bold>Methods:</jats:bold> In the present study, a flow-based blood testing platform, named leukocyte adhesive function assay (LAFA), was used to mimic blood microcirculation in vitro so that the patient leukocyte ability to interact with multiple endothelial molecules, including P+E selectins, VCAM-1 and IL-8, can be studied. The leukocyte adhesive functions of multiple leukocyte subsets were quantitatively assessed using a range of cell kinetic parameters, including cell speed, straightness, dwell time etc.<jats:bold>Results:</jats:bold> When analysed on P+E selectin substrate, a significantly lower value of cell straightness was observed in septic CD4 cells than non-infectious cells (0.78±0.04 vs 0.92±0.01, p &lt; 0.01), suggesting a difference in CD4 cells ability to adhere to selectins in infectious and non-infectious patients. Additionally, an impaired ability to respond to IL-8 was observed in septic neutrophils compared to non-infectious cells, evidenced by a significantly reduced cell dwell time (91.7±14.0 vs 150.6±19.0 seconds, p &lt; 0.05).<jats:bold>Conclusions:</jats:bold> Thus, our study promisingly showed the ability of LAFA to detect different adhesive function between leukocytes from ICU patients with infectious and non-infectious systemic inflammation. LAFA generated a number of novel markers that might distinguish infectious inflammation from non-infectious causes that warrant further study and novel opportunities for the rapid and accurate diagnosis of sepsis.</jats:p>

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