Abstract
ObjectivesType I interferons (IFNs) play an important role in the pathophysiology of systemic lupus erythematosus (SLE). While cross-sectional data suggest an association between IFN-induced gene expression and SLE disease activity, interest in this as a biomarker of flare has been tempered by a lack of fluctuation with disease activity in the majority of patients. This led us to question whether IFN-induced gene expression might instead be a biomarker of overall disease severity, with patients with high levels spending more time in an active disease state.MethodsLevels of five interferon-responsive genes were measured in the whole peripheral blood at baseline visit for 137 SLE patients subsequently followed for 5 years. Log transformed values were summed to yield a composite IFN5 score, and the correlation with various disease outcomes examined. Receiver operator characteristic analyses were performed for outcomes of interest. Kaplan-Meier curves were generated to compare the proportion of flare-free patients with high and low IFN5 scores over time.ResultsThe baseline IFN5 score was positively correlated with the adjusted mean SLE disease activity index-2000, number of flares, adjusted mean prednisone dose, and number of new immunosuppressive medications over the subsequent 5 years. Optimal cut-offs for the IFN5 score were determined using Youden’s index and predicted more severe outcomes with 57–67% accuracy. A high baseline IFN5 level was associated with a significantly increased risk of subsequent flare.ConclusionsMeasurement of the type I IFN signature is a useful tool for predicting the subsequent disease activity course.
Highlights
One of the most characteristic immunologic abnormalities associated with systemic lupus erythematosus (SLE) is elevation of type I interferons (IFNs) [1, 2]
These elevations have been difficult to detect in the blood using conventional ELISAs, a significant proportion of SLE patients have elevated levels of IFN-induced gene expression in their peripheral blood cells, suggesting that some of these cells have transited an environment with increased elaboration of type I IFN
Despite the lack of correlation between the IFN signature and disease activity in some previous studies, we previously showed that patients with high levels of IFNinduced gene expression were more likely to have had a recent flare of their disease and had a higher rate of subsequent flare [6]
Summary
One of the most characteristic immunologic abnormalities associated with systemic lupus erythematosus (SLE) is elevation of type I interferons (IFNs) [1, 2] These elevations have been difficult to detect in the blood using conventional ELISAs, a significant proportion of SLE patients have elevated levels of IFN-induced gene expression in their peripheral blood cells, suggesting that some of these cells have transited an environment with increased elaboration of type I IFN. In cross-sectional studies of SLE, elevated levels of IFN-induced gene expression, typically measured as scores incorporating expression of a subset of IFN-induced genes, were shown to correlate with disease activity [3,4,5,6]. There remains some controversy regarding this point, since even the genes reported to be more variable over time have not been shown to consistently correlate with disease activity in longitudinal studies [10]
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