Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital and School of Biomedical Engineering, Shanghai, 200030, China.
State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200001, China.
Adv Sci (Weinh). 2023 Dec;10(35):e2300123. doi: 10.1002/advs.202300123. Epub 2023 Oct 24.
Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4 T cells and loss of immune tolerance. However, the involvement of CD8 T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single-cell RNA sequencing. This is observed that CD8 CD27 CXCR3 T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8 CD27 CXCR3 T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin-2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score-related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8 CD27 CXCR3 T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.
系统性红斑狼疮(SLE)的发病机制强调了 CD4 T 细胞过度产生和免疫耐受丧失的作用。然而,CD8 T 细胞在 SLE 病理和疾病进展中的参与仍不清楚。在这里,通过质谱流式细胞术、流式细胞术和单细胞 RNA 测序,研究了总共 263 例临床外周血样本(包括活动期 SLE(aSLE)、缓解期 SLE(rSLE)和健康对照(HCs))中的全面免疫细胞失调。结果观察到,rSLE 中的 CD8 CD27 CXCR3 T 细胞比 aSLE 增加。同时,与 HCs 和 rSLE 相比,aSLE 中 CD8 CD27 CXCR3 T 细胞的效应功能过度活跃,并且与临床 SLE 活动呈正相关。此外,监测了 aSLE 和 rSLE 外周血单个核细胞(PBMCs)对白细胞介素-2 刺激的反应,以构建动态网络生物标志物(DNB)模型。结果表明,与 DNB 评分相关的参数可以准确预测 aSLE 的缓解和 rSLE 的发作。CD8 CD27 CXCR3 T 细胞的丰度和功能失调可作为 SLE 预后和伴随诊断的潜在生物标志物。具有 SLE 疾病进展准确预测能力的 DNB 评分可提供临床治疗建议,特别是用于确定药物剂量。