Identification of IFITM3 as a diagnostic biomarker of systemic lupus erythematosus and its association with disease activity based on multi-omics and experimental verification.

Abstract

Background: Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease that lacks reliable diagnostic biomarkers. In our study, we aimed to identify a novel biomarker for the diagnosis and disease activity monitoring of SLE.

Methods: Bulk RNA and scRNA-seq datasets were obtained from the Gene Expression Omnibus database. In this study, differential analysis, cell-cell communication algorithm, functional enrichment analysis, human protein map database analysis, protein-protein interaction analysis and immune cell infiltration analysis were utilized to identify the hub genes between SLE and healthy groups. Furthermore, clinical data from 68 SLE patients and 31 healthy controls were collected for verification. Changes in IFITM3 levels were confirmed through quantitative real-time polymerase chain reaction, western blotting, and flow cytometry analyses.

Result: Bioinformatic analyses showed that IFITM3 expression was significantly upregulated in peripheral monocytes from patients with SLE. IFITM3 mRNA levels showed a significant diagnostic value for SLE, with an AUC value of 87.14%. IFITM3 expression was associated with the systemic lupus erythematosus disease activity index, as well as C3, C4, and IgG levels. The results of Chi-square test showed that those in the IFITM3-positive group had a higher percentage of several clinical manifestations such as thrombocytopenia, leukopenia, low complement, and fever.

Conclusions: These findings indicated an obviously increased expression of IFITM3 in peripheral blood monocytes of patients with SLE and verified IFITM3 as a promising diagnostic marker for SLE and associated with disease activity.