HLA-DR expression on monocytes and the T-cell subset in septic patients

Introduction

Sepsis is one major cause of mortality in the ICU, despite increasing knowledge about its physiopathology, new generation of antibiotics and an advance in supportive therapy [1]. Interaction between microorganisms and toxins produced an activation of the immune system, resulting in release of proinflammatory and anti-inflammatory cytokines. Recent studies demonstrated an imbalance in the immune system during sepsis due to a high level of antinflmmatory cytokines, with a decrease of major histocompatibility leukocyte antigen (HLA-DR) on monocytes and alteration on total lymphocyte phenotype frequency.

Aim

To determine the time of HLA-DR expression in peripheral blood monocytes, variation in the lymphocyte subset, and their relationship with markers of inflammation, gravity score and development of sepsis.

Design

A prospective, longitudinal study.

Setting

A university hospital ICU.

Patients

Twenty consecutive medical patients admitted to the ICU, 13 with sepsis and seven noninfected, without haemopoietc cancer, immunodepression and chronic therapy with steroids.

Interventions

Daily SOFA score, IPS score and clinical sepsis criteria as defined by the ACCP/SCCM were checked. Serum procalcitonin, C-reactive protein, leukocyte antigens and lymphocyte subset features were serially recorded every day after arrival during all periods of stay in the ICU.

Measurements and results

The percentage of HLA-DR on monocytes was significantly depressed in septic patients, particularly related to worsening of disease. In patients with septic shock the lowest value of HLA-DR on monocytes was recorded; that value increases with resolution of sepsis-correlated organ failure. The area under the ROC curve for HLA-DR to discriminate sepsis was 0.86 (sensibility 94% and specificity 61% with cutoff 0.7). The CD4/CD8 T-cell ratio was reduced in septic patients compared with nonseptic patients; the nadir value was in patients with septic shock as the HLA-DR value. Procalcitonin, C-reactive protein and gravity scores were correlated with monocytic HLA-DR expression and CD4/CD8 T-cell ratio.

Conclusion

A decrease of monocyte expression of HLA-DR and the CD4/CD8 T-cell ratio occurred during infection disease. In septic shock signs of uncontrolled hyperinflammation are contemporary with a severely depressed cellular response. HLA-DR has a good sensibility and specificity to differentiate sepsis from other noninfectious conditions in critically ill patients.