T regulatory cells activation and distribution are modified in critically ill patients with acute respiratory distress syndrome: A prospective single-centre observational study - 08/08/19

Doi : 10.1016/j.accpm.2019.07.014

Sebastien Halter ^a,^b,^c,^{^{1
www.reapitie-univparis6.aphp.fr/.}}, Lucrèce Aimade ^b,^c, Michèle Barbié ^b, Hélène Brisson ^a,^{^{1
www.reapitie-univparis6.aphp.fr/.}}, Jean-Jacques Rouby ^a,^{^{1
www.reapitie-univparis6.aphp.fr/.}}, Olivier Langeron ^a,^{^{1
www.reapitie-univparis6.aphp.fr/.}}, David Klatzmann ^b,^c, Michelle Rosenzwajg ^b,^c, Antoine Monsel ^a,^b,^c,⁎, ^{^{1
www.reapitie-univparis6.aphp.fr/.}}
^a Multidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Public Hospitals of Paris (AP–HP), Sorbonne University, 75013 Paris, France
^b Public Hospitals of Paris (AP–HP), La Pitié-Salpêtrière Hospital, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), 75651 Paris, France
^c Sorbonne University, INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (i3), 75651 Paris, France

^⁎Corresponding author at: Polyvalent Critical Care Unit, Department of Anaesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital Group, 47–83, boulevard de l’Hôpital, 75651 Paris cedex 13, France.Polyvalent Critical Care Unit, Department of Anaesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital Group47–83, boulevard de l’HôpitalParis cedex 1375651France

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Abstract

Backgrounds

Acute respiratory distress syndrome (ARDS) is a common and fatal inflammatory condition. Whether T regulatory cells (Tregs) are beneficial or detrimental remains controversial, and longitudinal studies are lacking. Phenotyping of Tregs activation markers has been poorly reported. We aimed to evaluate quantitative and functional alterations in blood and bronchoalveolar Treg phenotype of ARDS patients.

Methods

We performed a single-centre observational study in a French intensive care unit. The study enrolled 60 ARDS and 45 non-ARDS patients. Patients under 18years old or with immunosuppression (native or acquired) were excluded. Tregs phenotypes were assessed by flow cytometry, while cytokines were measured by multiplex-based assays in blood and bronchoalveolar samples collected over 3weeks after the onset of ARDS.

Results

Blood Tregs/CD4+ percentage (median %, 25–75% interquartile) was higher in ARDS patients than in non-ARDS patients: 12.1% [9.0–16.0] versus 9.9% [8.1–12.6], P=0.01. Alveolar Tregs/CD4+ percentage was lower in ARDS patients than in non-ARDS patients: 10.4% [6.3–16.6] versus 16.2% [12.4–21.1], P=0.03. In ARDS patients, Tregs activation was reduced in the blood and increased in the alveolus, compared to non-ARDS patients. ROC analysis revealed a threshold of 10.4% for the Tregs/CD4+ percentage in the blood collected within the first week of ARDS to discriminate between survivors and non-survivors (sensitivity: 75%; specificity 76%; area under the curve [95% confidence interval]: 0.72 [0.5–0.9]).

Conclusions

Quantitative and functional alterations in Treg phenotype were observed in patients with ARDS. Whether rebalancing Tregs phenotype with therapeutic interventions would be beneficial deserves further investigations.

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Keywords : Acute respiratory distress syndrome, T regulatory cells, Immune phenotype, Innate lymphoid cells, T helper polarisation

Abbreviations : ARDS, BAL, CD, CTLA-4, FoxP3, GITR, HLA, ICU, IL, ILCs, IFN, IQR, LAG, LAP, NK, ROC, SAPS 2, SD, SOFA, Teff, TGF-β1, Th, TNF, Tregs, VAP