title: Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon β in dermatomyositis.
abstract: BACKGROUND
  Dermatomyositis (DM) is an autoimmune disease primarily affecting skin and muscle.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Pfizer Inc., Centers for Therapeutic Innovation, Boston, MA, U.S.A.
authors: C
authors: C
authors: Huard
authors: Pfizer Inc., Centers for Therapeutic Innovation, Boston, MA, U.S.A.
authors: S V
authors: SV
authors: Gullà
authors: Pfizer Inc., Pharma Therapeutics, Precision Medicine, Cambridge, MA, U.S.A.
authors: D V
authors: DV
authors: Bennett
authors: Pfizer Inc., Centers for Therapeutic Innovation, Boston, MA, U.S.A.
authors: A J
authors: AJ
authors: Coyle
authors: Department of Dermatology, Brigham and Women's Hospital, Boston, MA, U.S.A.
authors: R A
authors: RA
authors: Vleugels
authors: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, U.S.A.|Children's Hospital Informatics Program, Boston Children's Hospital, Boston, MA, U.S.A.
authors: S A
authors: SA
authors: Greenberg
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D003430:Cross-Sectional Studies; D003882:Dermatomyositis / Q000097:blood / Q000235:genetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007370:Interferon Type I; D012333:RNA, Messenger; D016899:Interferon-beta