• Manu Shankar-Hari, Deepankar Datta, Julie Wilson, Valentina Assi, Jacqueline Stephen, Christopher J Weir, Jillian Rennie, Jean Antonelli, Anthony Bateman, Jennifer M Felton, Noel Warner, Kevin Judge, Jim Keenan, Alice Wang, Tony Burpee, Alun K Brown, Sion M Lewis, Tracey Mare, Alistair I Roy, John Wright, Gillian Hulme, Ian Dimmick, Alasdair Gray, Adriano G Rossi, A John Simpson, Conway MorrisAndrewAUniversity Division of Anesthesia, Department of Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, UK., and Timothy S Walsh.
• School of Immunology & Microbial Sciences, Kings College, London, UK. manu.shankar-hari@kcl.ac.uk.
• Intensive Care Med. 2018 Nov 1; 44 (11): 1836-1848.

PurposeReliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).MethodsIn a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).ResultsBetween January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.ConclusionsFrom a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.Clinical Trial RegistrationNCT02188992.

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