A consensus immune dysregulation framework for sepsis and critical illnesses.

Although numerous immune endotypes have been proposed for sepsis and critical care, the similarities and differences between these endotypes remain unclear, hindering clinical translation.

尽管已经提出了许多针对败血症和重症监护的免疫内型，但这些内型之间的相似之处和差异仍然不清楚，这阻碍了临床转化。

The SUBSPACE consortium is an international consortium that aims to advance precision medicine in critical care through the sharing of transcriptomic data.

SUBSPACE联盟是一个国际联盟，旨在通过共享转录组数据来推进重症监护中的精准医学。

Here, evaluating the overlap of existing immune endotypes in sepsis across >7,074 samples from 37 independent cohorts, we developed cell-type-specific gene expression signatures to quantify dysregulation within immune compartments.

在这里，通过对来自37个独立队列的超过7074个样本进行评估，我们发现了脓毒症中现有免疫内型的重叠，并开发了针对特定细胞类型的基因表达特征，以量化免疫区室内的失调。

Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts.

髓系和淋巴系失调与所有队列中疾病的严重程度和死亡率相关。

Importantly, this dysregulation was also observed in patients with ARDS, trauma and burns, suggesting a conserved mechanism across various critical illness syndromes.

重要的是，这种失调也在急性呼吸窘迫综合征、创伤和烧伤患者中观察到，这表明在各种危重病综合征中存在一种保守的机制。

Moreover, analysis of randomized controlled trialdata revealed that myeloid and lymphoid dysregulation are associated with differential mortality in patients treated with anakinra in the SAVE-MORE trial (n = 452) and corticosteroids in the VICTAS (n = 89) and VANISH (n = 117) trials, underscoring their prognostic and therapeutic implications.

此外，对随机对照试验数据的分析揭示了骨髓和淋巴细胞失调与在SAVE-MORE试验（n = 452）中接受阿那金拉治疗的患者以及在VICTAS（n = 89）和VANISH（n = 117）试验中接受皮质类固醇治疗的患者的差异性死亡率相关，强调了它们的预后和治疗意义。

In conclusion, our proposed immunology-based framework for quantifying cellular compartment dysregulation offers a potentially valuable tool for understanding immune dysregulation in critical illness with prognostic and therapeutic significance.

总之，我们提出的基于免疫学的量化细胞区室失调的框架为理解重症疾病中的免疫失调提供了一个潜在有价值的工具，具有预后和治疗意义。