Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon β in dermatomyositis

Abstract

Dermatomyositis (DM) is an autoimmune disease primarily affecting skin and muscle. The purpose of this study was to determine whether an association exists between clinical skin disease activity as measured by the validated Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and type 1 interferon pathway biomarkers in the blood of DM patients. Forty-two patients with DM and 25 healthy volunteers were prospectively enrolled. CDASI scores were obtained, and serum and blood RNA were isolated from all participants. Associations between CDASI activity and type 1 interferon-inducible gene signature were assessed cross-sectionally in all patient samples and longitudinally on 13 paired visits via transcriptional profiling analyses. By RNAseq analysis, type 1 interferon-inducible genes were the most highly differentially regulated. A CDASI activity threshold of 12 was correlated with an elevated type 1 interferon gene signature and with serum interferon beta (IFNβ), but not with interferon alpha (IFNα) protein. Expression analysis showed that all patients with mild disease activity had a low type 1 interferon gene signature, while 93% of patients with moderate to high disease activity had elevated gene signature. In longitudinal analysis, changes in CDASI activity showed non-significant trends with concordant directional changes in gene signature. A type 1 interferon pathway signature biomarker in blood is highly correlated with CDASI activity scores in DM, and may be a promising surrogate clinical trial endpoint. The correlation of serum IFNβ, but not IFNα, with both a gene signature and CDASI suggests that IFNβ drives disease activity in DM.