Luo Qiang, Hao Han, Xiwen Luo, Qiu Xiang, Liu Dawei, Liu Yun, Li Fengning, Lu Kening, Luo Xiya, Ma Chenxi, Zhao Xiaodong, An Yunfei, Tang Xuemei
Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
School of Public Health, North China University of Science and Technology, Tangshan, 063000, China.
Arthritis Res Ther. 2025 Jul 9;27(1):140. doi: 10.1186/s13075-025-03606-8.
Early diagnosis is crucial for reducing disability and improving long-term prognosis in patients with systemic Juvenile Idiopathic Arthritis (sJIA), but it remains a significant challenge. This study aims to identify non-invasive biomarkers with superior diagnostic efficacy for sJIA.
To predict early potential biomarker candidates and pathogenic mechanisms for sJIA, we performed scRNA-seq and Bulk RNA-seq on PBMCs from the Chinese sJIA cohort. The findings were validated through in vitro experiments and cell sequencing. We also established the relationship between UBE2D1 and other systemic diseases to determine possible complications of sJIA.
Using scRNA-seq and Bulk RNA-seq, we discovered that UBE2D1 expression is closely related to disease activity levels, specifically in classical monocytes from sJIA patients. Functional enrichment suggested that UBE2D1 could enhance disease progression by activating NLRs. Follow-up data indicated a significant reduction in UBE2D1 expression and monocyte numbers before and after treatment. Pseudotime analysis revealed that UBE2D1 expression is initially high during monocyte development. Western blot results showed increased levels of UBE2D1 and NLRs marker proteins, which decreased upon introducing UBE2N and NF-κB inhibitors. Co-IP suggested that UBE2D1 mediates the activation of the NLRs pathway by interacting with IKB-α. The UBE2D1 complication map indicates that UBE2D1 might contribute to the development of various diseases across 17 different systems, including autoimmune diseases, the digestive system, and ocular conditions.
Our findings provide insights into the biological mechanisms of sJIA, indicating that UBE2D1, which is highly expressed in monocytes, may represent a candidate biomarker for early diagnosis and a potential method for clinical treatment strategies, pending further validation.
早期诊断对于降低全身型幼年特发性关节炎（sJIA）患者的残疾率和改善长期预后至关重要，但仍然是一项重大挑战。本研究旨在识别对sJIA具有卓越诊断效能的非侵入性生物标志物。
为了预测sJIA的早期潜在生物标志物候选物和致病机制，我们对中国sJIA队列的外周血单核细胞（PBMC）进行了单细胞RNA测序（scRNA-seq）和批量RNA测序（Bulk RNA-seq）。研究结果通过体外实验和细胞测序进行了验证。我们还建立了泛素结合酶E2D1（UBE2D1）与其他全身性疾病之间的关系，以确定sJIA可能的并发症。
通过scRNA-seq和Bulk RNA-seq，我们发现UBE2D1的表达与疾病活动水平密切相关，特别是在sJIA患者的经典单核细胞中。功能富集分析表明，UBE2D1可通过激活NLRs（核苷酸结合寡聚化结构域样受体）增强疾病进展。随访数据表明，治疗前后UBE2D1的表达和单核细胞数量显著减少。伪时间分析显示，UBE2D1在单核细胞发育初期表达较高。蛋白质免疫印迹结果显示，UBE2D1和NLRs标记蛋白水平升高，而引入UBE2N和核因子κB（NF-κB）抑制剂后其水平降低。免疫共沉淀表明，UBE2D1通过与IκB-α相互作用介导NLRs途径的激活。UBE2D1并发症图谱表明，UBE2D1可能与17个不同系统的多种疾病的发生有关，包括自身免疫性疾病、消化系统疾病和眼部疾病。
我们的研究结果为sJIA的生物学机制提供了见解，表明在单核细胞中高表达的UBE2D1可能代表一种早期诊断的候选生物标志物以及临床治疗策略的潜在方法，有待进一步验证。
