Lymphocyte phenotype during severe sepsis and septic shock

Introduction

Two major immuno-inflammatory phases are well documented during sepsis: an early active inflammatory phase regulated followed by a deactivated inflammatory phase leading to immunosuppression. Innate immunity, such as monocyte HLA-DR expression (mHLA-DR), has been shown constantly and rapidly decreased. Adaptive immunity modifications have been reported, this appeared less documented, particularly in comparison with healthy volunteers which have been rarely reported.

Objectives

The aim of this study is 1- to describe lymphocyte phenotypes in healthy volunteers 2- to study the phenotype in early (< D7) and late (>D7) phases of severe sepsis 3- to test the relation between lymphocyte phenotypes and prognosis.

Methods

Monocenter study on patients with severe sepsis and septic shock. Data recorded: demographic, clinical severity, blood cell count, mHLA-DR, lymphocyte phenotype (flow cytometry, CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+). Samples taken as part of routine care without additional blood collection and did not required patient´s consent. Patients data compared with a historical group of healthy volunteers from the laboratory. Statistics: results expressed as median (25^th-75^th percentile), Mann-Whitney test, Pearson correlation.

Results

45 septic patients (9 severe sepsis, 36 septic shock), age 66 (52-85), sex (29M/16F), origin of sepsis (pulmonary 30%, abdominal 35%, others 30%), SAPS2 at admission 51 (40-63), SOFA score (day of phenotype) 9 (5-13), overall mortality at day 7: 22% and day 28: 48%, delay between the inflammatory insult and lymphocyte phenotype was 2 days (1-10). 48 healthy volunteers in the control group: age 42 (31-55), sex (24M/24F). The overall lymphopenia in septic patients was -37% compared to controls, mainly due to CD4 T lymphocytes depletion (Table). This T lymphopenia was more marked in the early phase (< 7D) than in the late phase (>7D) (p = 0.006). Early lymphocyte phenotype was not associated with mortality at day 7; as was not late lymphocyte phenotype with mortality at day 28. There was a correlation between lymphopenia and mHLA-DR (r0.55, p0.00009). There was no correlation between lymphocyte phenotype and severity scores.

Table 1

Conclusions

In severe sepsis including shock, lymphopenia was predominant on CD4+ T lymphocytes, mainly at the early phase, in association with decreased expression of mHLA-DR, suggesting synergistic changes in innate and adaptive immunity. Such monitoring for innate and adaptive immunity may help to decide the suitable drug to boost immunity, such as IFNγ or IL-7.