Anti-U1-RNP antibody positivity is associated with elevated interferon-stimulated gene expression scores in systemic lupus erythematosus irrespective of disease activity: a transcriptome analysis in Japanese patients

OBJECTIVES: With the introduction of anifrolumab to clinical practice, there is a growing interest in identifying factors associated with interferon (IFN) activity in patients with systemic lupus erythematosus (SLE). An association between IFN-stimulated gene (ISG) expression and anti-U1-ribonucleoprotein (RNP) antibody positivity has been reported. However, data from Asians are scarce. In this study, we investigated clinical parameters associated with ISG expression in patients with SLE in Japan. METHODS: We utilized transcriptome data from 130 Japanese patients diagnosed with SLE from the ImmuNexUT database. We defined the ISG score as the average normalized expression levels of IFI27, IFI44, IFI44L, and RSAD2. The associations between clinical parameters and the ISG score were assessed. RESULTS: Clinical characteristics were compared between the low- and high-ISG-score groups. Clinical SLE disease activity index, anti-U1-RNP antibodies, and anti-Sjogren's syndrome antigen A (SS-A) antibodies were associated with the high-ISG-score group in multiple logistic regression analysis. Classification and regression tree analysis indicated that anti-U1-RNP antibody positivity was the best serological factor predicting the ISG score. Even among patients with clinically inactive disease, the ISG score was higher in those positive for than in those negative for anti-U1-RNP antibodies. CONCLUSIONS: Autoantibody profiles, especially anti-U1-RNP antibodies, are useful for predicting ISG scores in Asians.