Τίτλος:
High levels of monocytic myeloid-derived suppressor cells are associated
with favorable outcome in patients with pneumonia and sepsis with
multi-organ failure
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Myeloid-derived suppressor cells (MDSCs) are immature
myeloid cells with immunosuppressive functions sub-classified into
monocytic and polymorphonuclear MDSCs (M-MDSCs and PMN-MDSCs). Clinical
studies reported increased levels of MDSCs that were associated with
poor outcome in sepsis patients. Since sepsis patients exhibit signs of
inflammation and immunosuppression, MDSCs may provide benefit by
dampening deleterious inflammation in some patients. To test this
hypothesis, we measured MDSCs in critically ill sepsis patients with
pneumonia and multi-organ dysfunctions and a high likelihood of death.
Methods: This was a prospective multicenter observational cohort study
performed in eight ICUs in Athens and Thessaloniki, Greece, enrolling
critically ill patients with pneumonia and sepsis with multi-organ
dysfunctions. A flow cytometry approach using blood collected at study
inclusion in tubes containing lyophilized antibodies combined to
unsupervised clustering was developed to quantify M-MDSCs and PMN-MDSCs.
Results: Forty-eight patients were included, of whom 34 died within 90
days. At study inclusion, M-MDSCs and PMN-MDSCs were increased in sepsis
patients when compared to healthy subjects (3.07% vs 0.96% and 22% vs
2.1% of leukocytes, respectively; p < 10(-4)). Increased PMN-MDSCs were
associated with secondary infections (p = 0.024) and new sepsis episodes
(p = 0.036). M-MDSCs were more abundant in survivors than in patients
who died within 28 days (p = 0.028). Stratification of patients
according to M-MDSC levels revealed that high levels of M-MDSC were
associated with reduced 90-day mortality (high vs low M-MDSCs: 47% vs
84% mortality, p = 0.003, hazard ratio [HR] = 3.2, 95% CI 1.4-7.2).
Combining high M-MDSC levels with low Acute Physiology and Chronic
Health Evaluation (APACHE) II score improved patient stratification
(M-MDSCshigh/APACHE IIlow vs M-MDSCslow/APACHE IIlow: 20% vs 80%
90-day mortality, p = 0.0096, HR = 7.2, 95% CI 1.6-32). In multivariate
analyses high M-MDSCs remained correlated with improved survival in
patients with low APACHE II score (p = 0.05, HR = 5.26, 95% CI
1.0-27.8).
Conclusion: This is the first study to associate high levels of M-MDSCs
with improved survival in sepsis patients.
Συγγραφείς:
Schrijver, Irene T.
Karakike, Eleni
Theroude, Charlotte and
Baumgartner, Petra
Harari, Alexandre
Giamarellos-Bourboulis,
Evangelos J.
Calandra, Thierry
Roger, Thierry
Περιοδικό:
Intensive Care Medicine Experimental
Λέξεις-κλειδιά:
Sepsis; Pneumonia; Infection; Multi-organ dysfunction; Myeloid-derived
suppressor cells; Critically ill; Intensive care; APACHE II
DOI:
10.1186/s40635-022-00431-0
