title: Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course.
abstract: OBJECTIVE
  Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immunomodulating agents, we prospectively evaluated whether interferon (IFN)-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM.
  
  
  METHODS
  Peripheral blood and clinical data were collected from 51 patients with juvenile or adult DM prospectively over 2 study visits. We performed disease activity measurements and calculated whole-blood type I IFN gene and chemokine scores. We also measured serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6).
  
  
  RESULTS
  Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before adjustment for medication use (r = 0.33, P = 0.023) and with changes in the IFN chemokine score before and after adjustment for medication use (r = 0.53, P < 0.001 and r = 0.50, P < 0.001, respectively). Changes in muscle and extramuscular visual analog scale (VAS) scores correlated positively with changes in IFN gene and chemokine scores (P = 0.002, P < 0.001, P = 0.095, P < 0.001). Serum levels of IL-6, IL-8, and tumor necrosis factor α (TNFα) correlated positively with changes in global, muscle, and extramuscular VAS scores (P < 0.05).
  
  
  CONCLUSIONS
  Our findings suggest that changes in type I IFN gene and chemokine scores as well as in levels of IL-6, IL-8, and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunomodulating agents.
authors.affiliation: Division of Rheumatology, Mayo Clinic, Rochester, MN 55905, USA. reed.ann18@mayo.edu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
authors.forename: Erik
authors.initials: E
authors.lastname: Peterson
authors.forename: Hatice
authors.initials: H
authors.lastname: Bilgic
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Shreyasee
authors.initials: S
authors.lastname: Amin
authors.forename: Molly S
authors.initials: MS
authors.lastname: Hein
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Crowson
authors.forename: Floranne
authors.initials: F
authors.lastname: Ernste
authors.forename: Emily Baechler
authors.initials: EB
authors.lastname: Gillespie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000097:blood* / Q000175:diagnosis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D007370:Interferon Type I; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha