Messenger RNA expression of major histocompatibility complex class II genes in whole blood from septic shock patients
Messenger RNA expression of major histocompatibility complex class II genes in whole blood from septic shock patients
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DOI：
10.1097/01.ccm.0000150958.20209.a3
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发表时间：
2005-01-01
影响因子：
8.8
通讯作者：
Lepape, A
中科院分区：
文献类型：
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作者：
Pachot, A;Monneret, G;Lepape, A
目的：提出单核细胞上人白细胞抗原(HLA)-DR表达降低是脓毒症引起免疫抑制的主要特征。本研究的目的是研究脓毒性休克患者全血中一个基因面板的信使RNA （mRNA）表达，该基因面板对确保主要组织相容性复合体II类蛋白结构、转运和肽负载至关重要。设计：作者进行了队列研究。环境：本研究在一所大学医院的重症监护病房进行。研究对象：感染性休克患者（n = 41）和健康志愿者（n = 15）。测量和主要结果：通过定量逆转录聚合酶链反应，我们发现感染性休克患者全血中高度多态性的HLA-DRB1和非多态性的dra mRNA水平在休克发作后1-3天和4-10天与健康志愿者相比均显著降低。在编码不变链的基因、转录因子II类反激活子（CIITA）以及参与肽装载组织蛋白酶S、HLA-DMA和-DMB的酶中也观察到了这种特征。流式细胞术检测的HLA-DR单核细胞表面表达与全血HLA-DRB1和-DRA mRNA水平显著相关，与其他ciit调控基因HLA-DMA和不变链的mRNA水平相关性较低。在一小部分纯化单核细胞样本中也观察到HLA-DRB mRNA与细胞表面表达水平之间的相关性。在时间关系方面，幸存者的全血HLA-DRA、-DMA、-DMB、不变链和CIITA mRNA水平显著升高（p =.001），而非幸存者的表达仍然很低。结论：在脓毒性休克过程中可能出现MHC ii限制性抗原呈递所需的基因面板的整体转录下调。我们的研究结果表明，CIITA调控基因的转录恢复可能有助于幸存者中观察到的膜HLA-DR表达的恢复。这些在mRNA水平上获得的结果支持了先前关于单核细胞HLA-DR在蛋白水平上缺失的报道，从而证实了在脓毒症患者随访中测量单核细胞HLA-DR的潜力。
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 CIIT-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.