Tang Youzhou, Cao Qingtai, Liu Jishi, Zhuang Quan
Department of Nephropathy and Rheumatology, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.
The Critical Kidney Disease Research Center, Central South University, Changsha, Hunan, China.
Mediators Inflamm. 2025 Apr 10;2025:5531382. doi: 10.1155/mi/5531382. eCollection 2025.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and destruction of small blood vessels. AAV could be fatal if left untreated. Prompt diagnosis and treatment are crucial to protect AAV-related organs and tissue. Plasmapheresis, a therapeutic intervention aimed at removing harmful substances from the blood, devotes benefits to AAV treatment. However, the specific immune mechanism underlying its effectiveness remains unclear. In our research, we used single-cell RNA sequencing (scRNA-seq) to study the variation of peripheral blood mononuclear cells (PBMCs) before and after plasmapheresis in AAV patients. From this work, we explored a novel method for monocyte classification. In addition, flow cytometry was used to detect the relationship between the monocyte clusters and AAV activity under the new monocyte clustering method. Our scRNA-seq results revealed significant changes in monocyte clusters following treatment, which could be classified into three clusters (CD14+ monocytes, FCGR1A+ monocytes, and FCGR3A+ monocytes). In addition, our flow cytometry results showed that FCGR3A+ (CD16+) monocytes were positively correlated with AAV activity, whereas FCGR1A+ (CD16-CD64+) monocytes were negatively correlated with AAV activity. This may be related to the different biological effects of CD16 and CD64 on monocytes after interacting with the Fc region of ANCAs. In conclusion, our research sheds light on the immune landscape of AAV before and after plasmapheresis, identifying specific monocyte clusters linked to disease activity. These findings offer insights for novel monitoring methods and therapeutic targets in AAV.
抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)是一组自身免疫性疾病,其特征是小血管的炎症和破坏。若不治疗,AAV可能会致命。及时诊断和治疗对于保护与AAV相关的器官和组织至关重要。血浆置换是一种旨在从血液中清除有害物质的治疗干预措施,对AAV治疗有益。然而,其有效性背后的具体免疫机制仍不清楚。在我们的研究中,我们使用单细胞RNA测序(scRNA-seq)来研究AAV患者血浆置换前后外周血单核细胞(PBMC)的变化。通过这项工作,我们探索了一种新的单核细胞分类方法。此外,在新的单核细胞聚类方法下,使用流式细胞术检测单核细胞簇与AAV活动之间的关系。我们的scRNA-seq结果显示治疗后单核细胞簇有显著变化,可分为三个簇(CD14 +单核细胞、FCGR1A +单核细胞和FCGR3A +单核细胞)。此外,我们的流式细胞术结果表明,FCGR3A +(CD16 +)单核细胞与AAV活动呈正相关,而FCGR1A +(CD16 - CD64 +)单核细胞与AAV活动呈负相关。这可能与CD16和CD64与ANCA的Fc区域相互作用后对单核细胞的不同生物学效应有关。总之,我们的研究揭示了血浆置换前后AAV的免疫格局,确定了与疾病活动相关的特定单核细胞簇。这些发现为AAV的新型监测方法和治疗靶点提供了见解。