PMID- 15644645
OWN - NLM
STAT- MEDLINE
DCOM- 20050223
LR  - 20190706
IS  - 0090-3493 (Print)
IS  - 0090-3493 (Linking)
VI  - 33
IP  - 1
DP  - 2005 Jan
TI  - Messenger RNA expression of major histocompatibility complex class II genes in 
      whole blood from septic shock patients.
PG  - 31-8; discussion 236-7
AB  - OBJECTIVE: The decreased expression of human leukocyte antigen (HLA)-DR on 
      monocytes is proposed as a major feature of sepsis-induced immunodepression. The 
      objective of the present study was to investigate, in whole blood from septic 
      shock patients, the messenger RNA (mRNA) expression of a gene panel, which is 
      essential to ensure major histocompatibility complex class II protein structure, 
      transport, and peptide loading. DESIGN: The authors conducted a cohort study. 
      SETTING: This study was conducted in intensive care units at a university 
      hospital. SUBJECTS: The study included septic shock patients (n = 41) and healthy 
      volunteers (n = 15). MEASUREMENTS AND MAIN RESULTS: Using quantitative reverse 
      transcriptase-polymerase chain reaction, we found that the highly polymorphic 
      HLA-DRB1 and nonpolymorphic-DRA mRNA levels were significantly decreased in whole 
      blood from patients with septic shock compared with healthy volunteer both on 
      days 1-3 and 4-10 after the onset of shock. This profile was also observed for 
      genes encoding the invariant chain, the transcription factor class II 
      transactivator (CIITA), and the enzymes involved in the peptide loading cathepsin 
      S, HLA-DMA, and -DMB. The monocyte surface expression of HLA-DR measured by flow 
      cytometry was significantly correlated with the whole-blood mRNA levels of 
      HLA-DRB1 and -DRA and to a lesser extent with the other CIITA-regulated genes 
      HLA-DMA and invariant chain. The correlation between HLA-DRB mRNA and 
      cell-surface expression levels was also observed in a small subset of purified 
      monocyte samples. Regarding the temporal relationship, a significant increase of 
      whole-blood HLA-DRA, -DMA, -DMB, invariant chain, and CIITA mRNA level was 
      observed in survivors (p = .001), whereas expressions remained low in 
      nonsurvivors. CONCLUSIONS: 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.
FAU - Pachot, Alexandre
AU  - Pachot A
AD  - Department of Human Genetics, bioMerieux, Parc Club du Moulin a Vent, 33, avenue 
      du Docteur LEVY, 69693 Venissieux Cedex, France. 
      alexandre.pachot@eu.biomerieux.com
FAU - Monneret, Guillaume
AU  - Monneret G
FAU - Brion, Aurelie
AU  - Brion A
FAU - Venet, Fabienne
AU  - Venet F
FAU - Bohe, Julien
AU  - Bohe J
FAU - Bienvenu, Jacques
AU  - Bienvenu J
FAU - Mougin, Bruno
AU  - Mougin B
FAU - Lepape, Alain
AU  - Lepape A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Crit Care Med
JT  - Critical care medicine
JID - 0355501
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Trans-Activators)
SB  - IM
CIN - Crit Care Med. 2005 Jan;33(1):236-7. PMID: 15644679
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence/genetics
MH  - Antigen Presentation/genetics
MH  - *Critical Care
MH  - Down-Regulation
MH  - Female
MH  - Genes, MHC Class II/*genetics
MH  - HLA-DR Antigens/genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Hospital Mortality
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Monocytes/metabolism
MH  - Nuclear Proteins/genetics
MH  - Prognosis
MH  - RNA, Messenger/blood/*genetics
MH  - Reference Values
MH  - Shock, Septic/blood/*genetics/mortality
MH  - Survival Analysis
MH  - Trans-Activators/genetics
MH  - Transcription, Genetic/genetics
EDAT- 2005/01/13 09:00
MHDA- 2005/02/24 09:00
CRDT- 2005/01/13 09:00
PHST- 2005/01/13 09:00 [pubmed]
PHST- 2005/02/24 09:00 [medline]
PHST- 2005/01/13 09:00 [entrez]
AID - 00003246-200501000-00005 [pii]
AID - 10.1097/01.ccm.0000150958.20209.a3 [doi]
PST - ppublish
SO  - Crit Care Med. 2005 Jan;33(1):31-8; discussion 236-7. doi: 
      10.1097/01.ccm.0000150958.20209.a3.