Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock

OBJECTIVE: Severe thermal injury causes immune dysfunctions involving both pro- and anti-inflammatory mechanisms. It subsequently leads to a state of immune deficiency that shares some similarities with sepsis-induced immunosuppression. A hallmark of the latter is established by decreased monocyte human leukocyte antigen-DR (mHLA-DR) measurements. The main objective of the current study was to characterize the appearance and the duration of low mHLA-DR expression after severe burn as well as to determine its correlation with mortality and septic complications. DESIGN: Observational study. SETTING: Burn unit (intensive care unit) in a university hospital. PATIENTS: Severe burn patients (total burn surface area >30%, n = 14) and healthy individuals (n = 29). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were immunologically monitored during 15 days. We quantified mHLA-DR expression with a standardized flow cytometry protocol. Every patient presented with decreased mHLA-DR expression at days 2-3 after burn. Then, from days 4-6, this expression increased in patients who would survive whereas it remained low in nonsurvivors. As early as days 7-10 after burn, patients who were going to develop secondary septic shock exhibited significantly lower mHLA-DR expression in comparison with patients recovering without severe septic complications. Using quantitative reverse transcriptase-polymerase chain reaction, at days 4-6, we found that the RNA level of the nonpolymorphic HLA-DRA chain and the transcription factor class II transactivator were also significantly decreased compared with healthy controls; however, plasma cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-10) did not provide any significant prognostic information. CONCLUSIONS: Severe burn injury induced a marked reduction in mHLA-DR expression at both protein and messenger RNA levels. Its persistent decrease was associated with mortality and the development of septic complications.