Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study

Abstract

PurposeIntensive care unit (ICU)-acquired infections (IAI) result in increased hospital and ICU stay, costs and mortality. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine for the identification of patients at risk of IAI. We evaluated the association of the systemic mRNA expression of two host response biomarkers, CD74 and IL10, with IAI occurrence in a large cohort of ICU patients.MethodsICU patients were prospectively enrolled in a multicenter cohort study. Whole blood was collected on the day of admission (D1) and on day 3 (D3) and day 6 (D6) after admission. Patients were screened daily for IAI occurrence and data were censored after IAI diagnosis. mRNA expression levels of biomarkers were measured using RT-qPCR. Fine and Gray competing risk models were used to assess the association between gene expression and IAI occurrence.ResultsA total of 725 patients were analyzed. At least one IAI episode occurred in 137 patients (19%). After adjustment for shock and sepsis status at admission, CD74 and IL10 levels were found to be significantly associated with IAI occurrence [subdistribution hazard ratio (95% confidence interval) 0.67 (0.46–0.97) for CD74 D3/D1 expression ratio and 2.21 (1.63–3.00) for IL10 at D3]. IAI cumulative incidence was significantly different between groups stratified according to CD74 or IL10 expression (Gray tests p < 0.001).ConclusionOur results suggest that two immune biomarkers, CD74 and IL10, could be relevant tools for the identification of IAI risk in ICU patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-017-4805-1) contains supplementary material, which is available to authorized users.

Immune Profiling Panel: a proof of concept study of a new multiplex molecular tool to assess the immune status of critically-ill patients

“…Selection of the IPP markers was based on four pillars: 1) previous laboratory expertise in evaluating the performance and robustness of the markers in clinical trials (21-23) 2) good documentation of prognostic markers in literature (7, 24) 3) performance of the selected assays in duplex and multiplex in a classic qPCR setting 4) address a balanced representation of the pathways involved in diverse cells of both arms of the immunity. The pathways addressed by IPP include both innate and adaptive immune markers that were characterized in previous sepsis studies done in our laboratory.…”

Integrative research agenda for diagnosis in sepsis

“…Urinary antigen testing for legionella and streptococcus pneumoniae demonstrated rapid, accurate and noninvasive testing methods. The use of quantitative-real time polymerase chain reaction might impact the determination of immunoparalysis in critically ill patients with one study reporting a decrease in CD74 mRNA and high levels of IL-10 mRNA expression being associated with a higher risk of nosocomial infections in ICU (15). Another novel marker, Presepsin, a soluble CD14 subtype has also been identified as an early diagnostic indicator of sepsis as well as being implicated in assessment of sepsis severity and prognosis (16).…”

Sepsis: who will shoot first? Pharma or diagnostics?

“…However, such flow-cytometry-based approaches still currently limit inclusions to large/ university centers where such expertise is available. More accessible techniques will be needed to allow the implementation of immunotherapy more widely (e.g., CD74 mRNA expression by quantitative PCR, which has recently been validated as a molecular surrogate to mHLA-DR [14]). Moreover, given the complexity of the immune system, setting up a sepsis trial which truly addresses immune dysfunction in a personalized manner (such as the ongoing PROVIDE study, NCT03332225) will require assessment of both the innate and adaptive immune systems, and the extent of both the pro-and anti-inflammatory responses.…”