斯坦福大学Purvesh Khatri研究团队提出了保守的免疫失调特征与感染严重程度、感染前的危险因素和治疗反应有关。该研究于2025年6月17日发表于国际一流学术期刊《免疫学》杂志上。

该课题组假设在这些危险因素中存在一种保守的共同免疫失调。研究组整合了来自68个队列的12026份血液样本的单细胞和大量转录组学数据以及蛋白质组学数据来验证这一假设。小组发现他们之前描述的42个基因严重或轻微（SoM）特征与感染前的这些风险因素有关。

此外，这种保守的免疫特征可以通过免疫调节药物和生活方式的改变而改变。SoM评分预测了氢化可的松治疗对脓毒症患者的伤害，以及对单克隆抗体治疗无反应的哮喘患者。最后，SoM评分与全catheme死亡率相关。SoM特征有可能重新定义基线免疫状态的免疫框架以及对慢性、亚急性和急性疾病的反应。

据悉，年龄较大、男性、肥胖、吸烟和合并症（如糖尿病、哮喘）与严重感染风险增加有关。

附：英文原文

Title: A conserved immune dysregulation signature is associated with infection severity, risk factors prior to infection, and treatment response

Author: Ananthakrishnan Ganesan, Andrew R. Moore, Hong Zheng, Jiaying Toh, Michael Freedman, Andrew T. Magis, James R. Heath, Purvesh Khatri

Issue&Volume: 2025-06-17

Abstract: Older age, being male, obesity, smoking, and comorbidities (e.g., diabetes, asthma) are associated with an increased risk for severe infections. We hypothesized that there is a conserved common immune dysregulation across these risk factors. We integrated single-cell and bulk transcriptomic data and proteomic data from 12,026 blood samples across 68 cohorts to test this hypothesis. We found that our previously described 42-gene Severe-or-Mild (SoM) signature was associated with each of these risk factors prior to infection. Furthermore, this conserved immune signature was modifiable using immunomodulatory drugs and lifestyle changes. The SoM score predicted the individuals with sepsis who would be harmed by hydrocortisone treatment and individuals with asthma who would not respond to monoclonal antibody treatment. Finally, the SoM score was associated with all-cause mortality. The SoM signature has the potential to redefine the immunologic framing of the baseline immune state and response to chronic, subacute, and acute illnesses.

DOI: 10.1016/j.immuni.2025.05.020

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00241-9