Suppression of soluble T cell-associated proteins by an anti-interferon-α monoclonal antibody in adult patients with dermatomyositis or polymyositis

Rheumatology (Oxford). 2014 Apr;53(4):686-95. doi: 10.1093/rheumatology/ket413. Epub 2013 Dec 19.


Objective: The aim of this study was to identify serum markers that are modulated by an investigational anti-IFN-α mAb, sifalimumab, in adult DM or PM patients.

Methods: In a phase 1b clinical trial, sera were collected from a total of 48 DM or PM adult patients receiving either placebo for 3 months or sifalimumab for 6 months. Samples were tested for 128 selected proteins using a multiplex luminex immunoassay. Muscle biopsies from selected patients were stained for T cell infiltration using an anti-CD3 antibody.

Results: A robust overexpression of multiple serum proteins in DM or PM patients was observed, particularly in patients with an elevated baseline type I IFN gene signature in the blood or muscle. Neutralization of the type I IFN gene signature by sifalimumab resulted in coordinated suppression of T cell-related proteins such as soluble IL-2RA, TNF receptor 2 (TNFR2) and IL-18. Muscle biopsies from two patients with the highest serum protein suppression were selected and found to have a pronounced reduction of muscle T cell infiltration. Down-regulation of IL-2RA correlated with favourable manual muscle test 8 (MMT-8) alterations in sifalimumab-dosed patients.

Conclusion: A reduced level of multiple T cell-associated proteins after sifalimumab but not placebo administration suggests a suppressive effect of blocking type I IFN signalling on T cell activation and chemoattraction that may lead to a reduction of T cell infiltration in the muscle of myositis patients. Further, soluble IL-2RA changes from baseline may serve as a responsive and/or predictive marker for type I IFN-targeted therapy in adult DM or PM patients.

Keywords: T cell infiltration; dermatomyositis; polymyositis; soluble interleukin-2 receptor; type I interferon.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Dermatomyositis / drug therapy
  • Dermatomyositis / immunology*
  • Double-Blind Method
  • Down-Regulation
  • Female
  • Humans
  • Interferon-alpha / antagonists & inhibitors*
  • Interferon-alpha / genetics
  • Interleukin-18 / immunology
  • Interleukin-2 Receptor alpha Subunit / drug effects
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / immunology
  • Polymyositis / drug therapy
  • Polymyositis / immunology*
  • Receptors, Tumor Necrosis Factor, Type II / drug effects
  • Receptors, Tumor Necrosis Factor, Type II / immunology
  • Severity of Illness Index
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Treatment Outcome


  • ANGPT2 protein, human
  • Angiopoietin-2
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • IL2RA protein, human
  • Interferon-alpha
  • Interleukin-18
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Tumor Necrosis Factor, Type II
  • sifalimumab