Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis

J Invest Dermatol. 2015 Oct;135(10):2402-2409. doi: 10.1038/jid.2015.188. Epub 2015 May 20.


Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins and extracellular matrix (ECM) markers were measured in relation to IFN pathway activation status and SSc disease activity. Our results demonstrated a robust overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseline type I IFN gene signature. Anifrolumab administration was associated with significant downregulation of T cell-associated proteins and upregulation of type III collagen degradation marker. Whole-blood and skin microarray results also indicated the inhibition of T cell receptor and ECM-related transcripts by anifrolumab. In summary, our study demonstrates suppressive effects of anifrolumab on T cell activation and collagen accumulation through which tissue fibrosis may be reduced in SSc patients. The relationship between these peripheral markers and the clinical response to anifrolumab may be examined in larger double-blind, placebo-controlled trials.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Collagen Type I / drug effects
  • Collagen Type I / metabolism*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Infusions, Intravenous
  • Lymphocyte Activation / drug effects
  • Male
  • Patient Safety
  • Receptor, Interferon alpha-beta / administration & dosage
  • Receptor, Interferon alpha-beta / antagonists & inhibitors*
  • Risk Assessment
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / drug therapy*
  • Severity of Illness Index
  • T-Lymphocytes / drug effects
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Collagen Type I
  • IFNAR1 protein, human
  • Receptor, Interferon alpha-beta
  • anifrolumab