An increased alveolar CD4 + CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality

Intensive Care Med. 2013 Oct;39(10):1743-51. doi: 10.1007/s00134-013-3036-3. Epub 2013 Aug 16.

Abstract

Purpose: Cell therapy may become an option for lung injury treatment. However, no data are available on the alveolar presence and time course of CD4+ CD25 + Foxp3 + T-regulatory lymphocyte cells (Tregs) in acute respiratory distress syndrome (ARDS). Accordingly, we (1) measured the ratio of CD4 + CD25 + Foxp3 + Tregs to all (CD4+) lymphocytes in the bronchoalveolar lavage (BAL) of ARDS patients and of control subjects without lung disease and (2) assessed their impact on 30-day mortality.

Methods: In a prospective study, the ratios of CD4 + CD25 + Foxp3 + T-regulatory cells to all CD4+ cells were measured (FACS) within 24 h of the patients' ICU referral in the BAL and in the blood of 47 patients with ARDS (32 males, 15 females; mean age 44 years ±13) as well as in 8 controls undergoing elective abdominal surgery (5 men, 3 women; mean age 49 years ±4). BAL concentrations of several cytokines were also measured in ARDS patients.

Results: Tregs were detected in the BAL of control subjects and ARDS patients. However, the mean ratio of Tregs to all CD4+ lymphocytes was threefold greater in ARDS non-survivors (16.5%; p = 0.025) and almost twofold greater in ARDS survivors (9.0%; p = 0.015) compared to controls (5.9%). Multivariate Cox regression analysis revealed the ratio of CD4 + CD25 + Foxp3 + T-regulatory lymphocytes to all CD4+ lymphocytes in the BAL to be an important and independent prognostic factor for 30-day survival (HR 6.5; 95% CI, 1.7-25; p = 0.006).

Conclusion: An increased T-regulatory cell ratio in the admission BAL of patients with ARDS is an important and independent risk factor for 30-day mortality.

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Community-Acquired Infections / complications
  • Female
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / immunology*
  • Germany / epidemiology
  • Humans
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Male
  • Middle Aged
  • Pneumonia / complications
  • Prognosis
  • Prospective Studies
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / immunology*
  • Respiratory Distress Syndrome / mortality*
  • T-Lymphocytes, Regulatory / immunology
  • Time Factors

Substances

  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit