Messenger RNA expression of major histocompatibility complex class II genes in whole blood from septic shock patients*

Abstract

A global transcriptional down regulation of a gene panel required for MHC II-restricted antigen presentation may occur in the course of septic shock. Our results suggest that the transcriptional resumption of CIITA-regulated genes might contribute to the recovery of membrane HLA-DR expression observed in survivors. These results obtained at the mRNA level support previous reports describing the loss of monocyte HLA-DR at the protein level and thus confirm the potential of measuring monocyte HLA-DR in septic patient followup.

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

“…Decreased mHLA-DR was even found to be a better predictor of mortality than SAPS II and SOFA scores (110). In parallel, we demonstrated that the loss of mHLA-DR expression was due to a global regulation at the transcriptional level of all MHC class II restricted genes and that the magnitude of this regulation affected clinical outcome (111).…”

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

“…Levels of class II gene expression also vary in antigen-presenting cells dependent on particular stimuli. MHC class II gene expression may become markedly downregulated in particular physiological or disease states, for example, during severe or prolonged infection [26][27][28] or B-cell lymphoma 29 in which it is associated with poor outcome.…”

Is the measurement of monocytes HLA-DR expression useful in patients with sepsis?

“…The molecular mechanisms of HLA-DR downregulation at the surface of monocytes from critically ill patients are now better understood. HLA-DR production is impaired, and is retained intracellularly [7,8,9,10]. Interestingly, this monocyte phenotype can be reversed by the treatment of septic patients with interferon-γ or granulocyte-monocyte colony-stimulating factor [11,12,13].…”