Increases in inflammatory and CD14dim/CD16pos/CD45pos patrolling monocytes in sepsis: correlation with final outcome

Gabriela Gainaru, Antonios Papadopoulos, Iraklis Tsangaris, Malvina Lada, Evangelos J Giamarellos-Bourboulis, Aikaterini Pistiki, Gabriela Gainaru, Antonios Papadopoulos, Iraklis Tsangaris, Malvina Lada, Evangelos J Giamarellos-Bourboulis, Aikaterini Pistiki

Abstract

Background: Evidence on the changes in the absolute counts of monocyte subpopulations in sepsis is missing.

Methods: Firstly, absolute counts of circulating CD14pos/HLA-DRpos/CD45pos monocytes were measured by flow cytometry in 70 patients with Gram-negative sepsis and in 10 healthy volunteers. In the second phase, immunophenotyping was performed and the absolute count of circulating inflammatory monocytes and of circulating CD14dim/CD16pos/CD45pos patrolling monocytes were measured in another 55 patients and 10 healthy volunteers. Measurements were repeated on days 3, 7, and 10. Results were correlated with survival after 28 days.

Results: Greater numbers of CD14pos/HLA-DRpos/CD45pos monocytes were found on day 1 in survivors compared to nonsurvivors (p = 0.030). Receiver operating characteristic (ROC) analysis showed that a cutoff higher than 337 cells/mm3 on day 1 could discriminate between survivors and nonsurvivors with a positive predictive value (PPV) of 91.1%. Logistic regression including Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score showed that an absolute count greater than 337 cells/mm3 was independently associated with unfavorable outcome (odds ratio (OR) 0.19, p = 0.050). The absolute counts of inflammatory and of CD14dim/CD16pos/CD45pos monocytes were greater in patients than healthy controls during the entire 10 days of follow-up. The absolute counts on day 3 of CD14dim/CD16pos/CD45pos monocytes were greater in survivors than nonsurvivors (p = 0.027). ROC analysis revealed that the cutoff at 27 cells/mm3 could discriminate between survivors and nonsurvivors with PPV of 94.1%. Logistic regression including age, SOFA score, and APACHE II score showed that an absolute count greater than 27 cells/mm3 was independently associated with unfavorable outcome (OR 0.06, p = 0.033). Logistic regression analysis showed that intra-abdominal infection on day 1 was predictive of low CD14dim/ CD16pos/CD45pos count on day 3.

Conclusion: Circulating counts of inflammatory and patrolling monocytes are greatly increased in Gram-negative sepsis. Absolute counts of CD14pos/HLA-DRpos/CD45pos monocytes on day 1 and CD14dim/CD16pos/CD45pos monocytes on day 3 are independently associated with final outcome.

Trial registration: ClinicalTrials.gov, NCT01223690 . Registered retrospectively on 18 October 2010.

Keywords: Gram-negative; Inflammatory monocytes; Patrolling monocytes; Sepsis; Survival.

Conflict of interest statement

Ethics approval and consent to participate

This study constitutes a substudy of a large prospective randomized clinical trial (registration NCT012236690). The study was approved by the ethics committee of “ATTIKON” University Hospital (266/27-07-9). Patients were enrolled after written informed consent provided by themselves or by their legal representative for patients unable to consent.

Consent for publication

Patients or legal representatives consented to the publication of clinical data.

Competing interests

EJGB has received honoraria for providing scientific advice to AbbVie (Chicago IL, USA), Astellas (Athens, Greece), Biotest AG (Dreieich, Germany), and ThermoFisher Scientific GmbH (Henningdorf, Germany). He has received unrestricted educational funding from Biotest AG, ThermoFisher Scientific GmbH, Sanofi SA, (Athens, Greece), the Seventh Framework European Program HemoSpec, and the Horizon 2020 Marie-Curie grant European Sepsis Academy. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flow during the two phases
Fig. 2
Fig. 2
Association between final outcome and absolute counts of circulating CD14pos/HLA-DRpos/CD45pos monocytes. a Absolute counts of CD14pos/HLA-DRpos/CD45pos monocytes of survivors and nonsurvivors on days 1 and 3 and healthy volunteers. P values refer to comparisons between survivors and nonsurvivors. b ROC curve of the absolute count of CD14pos/HLA-DRpos/CD45pos monocytes on day 1 to predict survival after 28 days. c Predictive value of an absolute count of CD14pos/HLA-DRpos/CD45pos monocytes more than 337 cells/mm3 on day 1 for survival after 28 days. d) Comparative survival in relation to the absolute count of CD14pos/HLA-DRpos/CD45pos monocytes on day 1. AUC area under curve, CI confidence interval, NPV negative predictive value, PPV positive predictive value, Sens sensitivity, Spec specificity
Fig. 3
Fig. 3
Absolute counts of monocyte subpopulations in sepsis. a Absolute counts of inflammatory monocytes and of b CD14dim/CD16pos/CD45pos patrolling monocytes of healthy controls and of patients with sepsis on days 1 and 3. c Absolute counts of inflammatory monocytes and of d CD14dim/CD16pos/CD45pos patrolling monocytes of patients with sepsis on days 1 and 3 divided into those without and those with acute kidney injury (AKI). P values refer to the indicated comparisons
Fig. 4
Fig. 4
Association between final outcome and absolute counts of circulating CD14dim/CD16pos/CD45pos patrolling monocytes on day 3. a Absolute counts of inflammatory monocytes of survivors and nonsurvivors on days 1 and 3 and healthy volunteers. P values refer to comparisons between survivors and nonsurvivors. b Absolute counts of CD14dim/CD16pos/CD45pos patrolling monocytes of survivors and nonsurvivors on days 1 and 3 and healthy volunteers. P values refer to comparisons between survivors and nonsurvivors. c ROC curve of the absolute count of patrolling monocytes on day 3 to predict survival after 28 days. d Predictive value of an absolute count of patrolling monocytes greater than 27 cells/mm3 on day 3 for survival after 28 days. e Comparative survival for patients according to the number of patrolling monocytes on day 3. AUC area under curve, CI confidence interval, NPV negative predictive value, PPV positive predictive value, Sens sensitivity, Spec specificity

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Source: PubMed

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