Department of Pulmonary and Critical Care Medicine, the Chinese PLA General Hospital, Beijing, China.
Department of Respiratory and Critical Care Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Scand J Immunol. 2020 Jan;91(1):e12813. doi: 10.1111/sji.12813. Epub 2019 Nov 10.
Sepsis is a life-threatening disease that is an immune disorder response that causes multiple organ dysfunction. In this study, we investigated the dynamic changes in mRNA expression of HLA-DRA gene and the specific transcription factor of helper T cell subsets to explore long-term immunophenotyping and its relationship with prognosis.
Seventy-eight sepsis patients and twelve healthy controls were recruited in this study. Blood samples were collected at eight-time points during their septic course and were assayed for the gene expression of HLA-DRA and T helper cell subset-specific transcription factors (T-bet: Th1, GATA3: Th2, Foxp3: Treg, RORC: Th17).
The levels of HLA-DRA in survivors gradually increased but were maintained at lower levels in non-survivors. The specific transcription factor of Th1 and Th2 cells, T-bet and GATA-3 were significantly lower in sepsis patients than in normal controls, and the non-survivors showed significantly lower levels than the survivors (P < .05). RORC and FOXP3, the specific transcription factor of Treg and Th17 were significantly higher in survivors than in non-survivors and normal controls (P < .05). T-bet and GATA-3 had a linear correlation with HLA-DRA expression (P < .01).
The dynamic changes in HLA-DRA expression in peripheral blood could accurately reflect the immune status of sepsis patients, and the reduction in HLA-DRA may be an important reason for abnormal T cell differentiation. The sustained low levels of the Th cell subsets (Th1 and Th2) suggest the suppression of adaptive immunity, and this persistent immunosuppression may be the leading cause of death in septic patients.
脓毒症是一种危及生命的疾病，是一种免疫紊乱反应，可导致多器官功能障碍。在这项研究中，我们研究了 HLA-DRA 基因和辅助性 T 细胞亚群特异性转录因子的 mRNA 表达的动态变化，以探讨长期免疫表型及其与预后的关系。
本研究纳入了 78 例脓毒症患者和 12 例健康对照者。在脓毒症病程的 8 个时间点采集血样，检测 HLA-DRA 基因和辅助性 T 细胞亚群特异性转录因子（T-bet：Th1，GATA3：Th2，Foxp3：Treg，RORC：Th17）的基因表达。
幸存者的 HLA-DRA 水平逐渐升高，但在非幸存者中维持在较低水平。Th1 和 Th2 细胞的特异性转录因子 T-bet 和 GATA-3 在脓毒症患者中明显低于正常对照组，且非幸存者明显低于幸存者（P<.05）。幸存者的 RORC 和 FOXP3，即 Treg 和 Th17 的特异性转录因子明显高于非幸存者和正常对照组（P<.05）。T-bet 和 GATA-3 与 HLA-DRA 表达呈线性相关（P<.01）。
外周血 HLA-DRA 表达的动态变化能准确反映脓毒症患者的免疫状态，HLA-DRA 的减少可能是 T 细胞分化异常的重要原因。辅助性 T 细胞亚群（Th1 和 Th2）的持续低水平提示适应性免疫受到抑制，这种持续的免疫抑制可能是脓毒症患者死亡的主要原因。
