Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2024 Mar 27;15:1374787. doi: 10.3389/fimmu.2024.1374787. eCollection 2024.
Acute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.
Employing a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.
Our investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28 CD45RA CD8 T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8 T cells in the pathophysiology of AP and its progression to sepsis.
This study elucidates the critical role of specific immune cell traits, particularly CD127 memory CD8 T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.
急性胰腺炎（AP）是一种严重的消化系统疾病，有发展为脓毒症的高风险，脓毒症是导致死亡的主要原因。阐明 AP 中的免疫途径对于开发有效的治疗方法至关重要，特别是要了解特定免疫细胞特征在这一进展中的作用。
本研究采用双向两样本孟德尔随机化（MR）方法，首先检查了 AP 与 731 种免疫细胞特征之间的因果关系，以确定与 AP 显著相关的特征。随后，我们探讨了 731 种免疫细胞特征与脓毒症之间的因果关联。该分析利用了广泛的全基因组关联研究（GWAS）汇总数据集，重点识别了在 AP 和脓毒症之间具有统计学显著因果关联的常见免疫细胞特征。
我们的研究确定了 44 种免疫细胞特征与 AP 单向相关，36 种特征与脓毒症单向相关。其中，CD28 CD45RA CD8 T 细胞上的 CD127 是一个共同的中介物，占 AP 患者脓毒症风险增加的 5.296%。这一发现突出了特定记忆 CD8 T 细胞在 AP 病理生理学及其向脓毒症进展中的重要作用。
本研究阐明了特定免疫细胞特征，特别是 CD127 记忆 CD8 T 细胞，在 AP 向脓毒症进展中的关键作用。我们的发现为未来针对免疫调节治疗的研究提供了基础，可能改善与 AP 相关的脓毒症患者的预后，并为该疾病复杂的免疫动态提供新的见解。
