Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon beta in dermatomyositis
BRITISH JOURNAL OF DERMATOLOGY | AUGUST 26, 2016
Huard C, Gulla SV, Bennett DV, Coyle AJ, Vleugels RA and Greenberg SA
British Journal of Dermatology
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 (IFN) pathway biomarkers in the blood of patients with DM.
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 IFN‐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 IFN‐inducible genes were the most highly differentially regulated. A CDASI activity threshold of 12 was correlated with an elevated type 1 IFN gene signature and with serum IFN‐β, but not with IFN‐α protein. Expression analysis showed that all patients with mild disease activity had a low type 1 IFN gene signature, while 93% of patients with moderate‐to‐high disease activity had elevated gene signature. In longitudinal analysis, changes in CDASI activity showed nonsignificant trends with concordant directional changes in gene signature.
A type 1 IFN pathway signature biomarker in blood is highly correlated with CDASI activity scores in DM, and may be a promising surrogate clinical trial end point. The correlation of serum IFN‐β, but not IFN‐α, with both a gene signature and CDASI suggests that IFN‐β drives disease activity in DM.