Treatment with interferon 1 has been shown to induce polymyositis and other auto-immune diseases, and interferon 1 has been shown to be upregulated in a high percentage of cases of both polymyositis and dermatomyositis. Regulation of interferon 1 may be a target for therapy. (Wlash 2007).[1] 

Also see (Lundbeg, Helmers 2010). [2]

Important study on interferon interaction with immature muscle cells is "Immature muscle precursors are a source of interferon-β in myositis: role of Toll-like receptor 3 activation and contribution to HLA class I up-regulation". (Tournadre 2012). [3]

 

Interferons

The disease mechanisms that cause muscle damage and dysfunction are not fully understood. However, because of the association with other autoimmune diseases, the presence of autoantibodies, and response to immunosuppressive medication, they are believed to be autoimmune in origin.(1)

Muscle weakness, elevated muscle enzymes, and inflammation are characteristic features of idiopathic inflammatory myopathies (IIMs), but the exact pathways that trigger and maintain the muscle damage are currently unclear(1)

Serum Levels

Microarray gene studies have identified marked type I interferon (IFNα and IFNβ) signature in DM muscle compared to other forms of myositis (Greenberg, 2010). Greenberg et al. (2012) evaluated the correlation between cytokine-induced gene expression and disease activity in 24 patients with PM. The study revealed that a type 1 IFN signature in the blood was highly correlated with disease activity and decreased significantly in response to immunosuppressive therapy. This study provides insight into the significance of type I interferons in the pathophysiology of PM, suggesting that targeting type I interferons has therapeutic benefits.(1)

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. (2)

Relevance

Evidence accumulates implicating interferons (IFNs) in the chronic inflammation associated with the idiopathic inflammatory mypathies (IM). An IFN score in myositis patients is associated with the presence of myositis specific or associated autoantibodies Jo-1, U1RNP, Ro-52, Ro-60 or La and the association was stronger when 2 or more autoantibodies were present. Based on these data and on previous studies the authors hypothesise that these autoantibodies could act as an endogenous trigger of the type I IFN pathway and contribute to the chronicity of these diseases. (3)

Footnotes

1. Arash H. L. Polymyositis and Dermatomyositis: Novel Insights into the Pathogenesis and Potential Therapeutic Targets. Division of Rheumatology, Johns Hopkins University School of Medicine. Published on June 26, 2015. http://www.discoverymedicine.com/Arash-H-Lahouti/2015/06/polymyositis-and-dermatomyositis-novel-insights-into-the-pathogenesis-and-potential-therapeutic-targets/

2. Xiang G.Suppression of soluble T cell-associated proteins by an anti-interferon-α monoclonal antibody in adult patients with dermatomyositis or polymyositis . Rheumatology (2013) doi: 10.1093/rheumatology/ket41. http://rheumatology.oxfordjournals.org/content/early/2013/12/19/rheumatology.ket413.short

3. Saskia V.IFN signature is associated with autoantibody profiles in patients with myositis. Ann Rheum Dis 2012;71:A49 doi:10.1136/annrheumdis-2011-201235.16 . http://ard.bmj.com/content/71/Suppl_1/A49.1.short

 

 

 

Footnotes:

1. Walsh RJ, Kong SW,Yao Y,Jallal B,Kiener PA,Pinkus JL,Beggs AH,Amato AA,Greenberg SA. Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum, 56(11):3784-92, 2007 as found at VIEW

2. Jundberg IS, . The type I interferon system in idiopathic inflammatory myopathies. Autoimmunity, 43(3):239-43, 2010 as found at VIEW

3. Tournadre A, Lenief V,Eljaafari A, Miossec P. Immature muscle precursors are a source of interferon-β in myositis: role of Toll-like receptor 3 activation and contribution to HLA class I up-regulation. Arthritis Rheum, 64(2):533-41 , 2012 as found at VIEW