Automated whole-blood detection of <i>IFI27</i> and <i>OAS1</i> mRNA for distinguishing active systemic lupus erythematosus

OBJECTIVE: The aim of this study was to establish a fast, practical and automated assay to measure the expression of interferon-stimulated genes (ISGs) in whole peripheral blood and evaluate the utility of these markers in distinguishing active systemic lupus erythematosus (SLE). METHODS: A total of 102 SLE patients (38 active, 64 inactive) were enrolled. The mRNA levels of five ISGs (IFI27, OAS1, IFI44L, LY6E, IFIT1) in whole blood were quantified using an automated multiplex RT-qPCR platform. Multivariable linear regression was performed to evaluate the influence of medications and specific autoantibodies on ISG expression. Diagnostic performance was evaluated via receiver operating characteristic (ROC) curves. Backward stepwise logistic regression was employed to identify optimal predictors and subsequently construct a diagnostic probability matrix for disease activity. RESULTS: ISGs expression were significantly elevated in active SLE patients (2.9 ∼ 17.3 fold) and positively correlated with disease activity indictors. Multivariable analysis confirmed that ISGs expression reflected disease activity independent of treatments and autoantibody status. Subsequently, IFI27 and OAS1 were identified as the optimal combination, forming the ISG2 Score. Multivariable analysis confirmed that the ISG2 Score and complement-3 (C3) were independent predictors of active SLE. An ISG2-C3 matrix was developed and revealed a dramatic stepwise escalation in disease probability. Notably, we observed that elevated IFI27 in clinically inactive patients was associated with persistent leukopenia. CONCLUSION: This automated whole-blood assay offers a rapid and reliable method for ISGs detection. IFI27 and OAS1 combined with C3, serve as sensitive biomarkers for monitoring of active SLE in routine care.