UBE2D1 as a key biomarker in systemic juvenile idiopathic arthritis: a new perspective on diagnosis and disease activity assessment.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.