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

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

Author information

1
MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA. guox@medimmune.com.

Abstract

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

PMID:
24357810
PMCID:
PMC3970566
DOI:
10.1093/rheumatology/ket413
[Indexed for MEDLINE]
Free PMC Article

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