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. 2021 Jan 16;23(1):29.
doi: 10.1186/s13075-021-02414-0.

The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus

Lloyd Mai  1 , Arundip Asaduzzaman  1 , Babak Noamani  2 , Paul R Fortin  3 , Dafna D Gladman  1   4 , Zahi Touma  1   4 , Murray B Urowitz  1   4 , Joan Wither  5   6   7   8
Affiliations

The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus

Lloyd Mai et al. Arthritis Res Ther. .

Abstract

Objectives: Type 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.

Methods: Levels 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.

Results: The 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.

Conclusions: Measurement of the type I IFN signature is a useful tool for predicting the subsequent disease activity course.

Keywords: Disease course; Interferon; SLEDAI-2K; Systemic lupus erythematosus.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Association between the baseline IFN5 score and disease severity in the subsequent 5 years. Correlation between the IFN5 score and specific disease outcomes. Each open circle represents an individual patient. Boxes show the Spearman correlation coefficient and p value for each outcome
Fig. 2
Fig. 2
Ability of the baseline IFN5 score to predict disease outcomes over the subsequent 5 years. ROCs are shown for various disease outcomes, with AUCs indicated
Fig. 3
Fig. 3
High IFN5 scores are associated with an increased risk of disease flare. Kaplan-Meier curves showing the proportion of flare-free patients over time. The significance of the differences between curves was determined using the Gehan-Breslow-Wilcoxon test
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