Abstract
PurposeCellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.MethodsMulti-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.ResultsA total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00–4.74), 3.44 (1.58–7.47) and 2.41 (1.14–5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.ConclusionsThis study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.Trial registrationThe study was registered with clinicaltrials.gov (NCT02186522).
Highlights
Critical illness occurs when a sterile [1, 2] or infective [3] insult leads to organ dysfunction [4]
We previously published the findings of a singlecentre study examining three markers associated with immune dysfunction [3], namely neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and the proportion of regulatory T cells (Tregs, associated with an increased risk of secondary infection [14])
Immunophenotyping measures The primary measures were those used in the published study [3], namely surface neutrophil CD88, monocyte HLA-DR and the proportion of CD4 T cells expressing a regulatory phenotype (CD4+/CD25++/CD127− Tregs) [3, 20]
Summary
Critical illness occurs when a sterile [1, 2] or infective [3] insult leads to organ dysfunction [4]. We previously published the findings of a singlecentre study examining three markers associated with immune dysfunction [3], namely neutrophil CD88 (as a marker of C5a-mediated neutrophil dysfunction [10, 11]), monocyte human leucocyte antigen-DR (HLA-DR) (as a marker of monocyte deactivation [12, 13]) and the proportion of regulatory T cells (Tregs, associated with an increased risk of secondary infection [14]) These three markers independently, and additively, predicted the subsequent development of nosocomial infection [3]. The first infection was defined as the outcome of interest
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
