Type 1 interferon status in systemic lupus erythematosus: a longitudinal analysis

Objectives Type 1 interferon (IFN) is key to the pathogenesis of SLE, evidenced by the expression of IFN-stimulated genes (ISGs) in most patients, but the clinical utility of serial ISG assessment remains unknown. With the emergence of IFN-blocking drugs, we aimed to examine IFN status in relation to clinical findings longitudinally to provide insights into the value of testing ISG levels over time. Methods Clinical data and whole blood were collected prospectively on adult patients with SLE from a single tertiary lupus centre. IFN status was measured using a panel of ISGs. Findings 729 samples were analysed from 205 patients. At baseline, 62.9% of patients were IFN high, 30.2% IFN low and 6.8% borderline. 142 patients had multiple samples collected, and 87.3% of these demonstrated stable ISG status over time. In longitudinal follow-up, IFN high patients had higher activity in multiple organ domains and spent less time in Lupus Low Disease Activity State, but IFN score did not correlate with SLE Disease Activity Index in individual patients. In the small subset of patients who had large fluctuations in ISG across the observation period, most had high-dose glucocorticoids that correlated with ISG suppression. However, low-moderate-dose glucocorticoids did not suppress ISG expression. Conclusion Although IFN high status is associated with indicators of more severe SLE, in the majority of patients, ISGs are stable across time and do not correlate with disease activity. Changes in ISG expression may be seen with high-dose, but not routine dose, glucocorticoid exposure. These findings suggest baseline but not serial ISG measurement may be of value in the management of SLE.

Automated summary

This study found that ISG levels are stable over time in the majority of SLE patients and do not correlate with disease activity, although IFN high status is associated with more severe SLE. High-dose glucocorticoids can suppress ISG expression, while routine dose does not.