title: Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab.
  
  
  METHODS
  In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed.
  
  
  RESULTS
  Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab.
  
  
  CONCLUSIONS
  IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.
authors.affiliation: Division of Rheumatology, Department of Pediatrics, Mayo Clinic, Rochester, USA.
authors.forename: Consuelo M
authors.initials: CM
authors.lastname: López De Padilla
authors.affiliation: Division of Rheumatology, Department of Pediatrics; and Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, USA.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Crowson
authors.affiliation: Division of Rheumatology, Department of Pediatrics, Mayo Clinic, Rochester, USA.
authors.forename: Molly S
authors.initials: MS
authors.lastname: Hein
authors.affiliation: Department of Surgical Research, College of Medicine, Mayo Clinic, Rochester, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Strausbauch
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Levesque
authors.affiliation: Division of Rheumatology, University of Miami, Miami, FL, USA.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Chester V
authors.initials: CV
authors.lastname: Oddis
authors.affiliation: Department of Pediatrics, Duke Children's Hospital, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018925:Chemokines; D016898:Interferon-alpha; D000069283:Rituximab