Background/Purpose: Idiopathic inflammatory myopathies (IIM) are rare autoimmune diseases characterized by proximal muscle weakness and muscle inflammation. IIM are associated with several autoantibodies, which are believed to play a role in its pathogenesis. Recent studies showed involvement of an activated type I IFN pathway in a subset of patients. Here we studied the possible relationship between autoantibody specificity and type I IFN pathway activation.

Methods: Ninety-four IIM patients, diagnosed with polymyositis (PM) (n=46), dermatomyositis (DM) (n=42), or inclusion body myositis (IBM) (n=6), 47 patients with systemic lupus erythematosus (SLE) and 43 healthy controls (HC) were included. Autoantibody profiles were assessed using lineblots. A whole blood IFN score was determined in all patients and healthy controls by measuring and averaging expression levels of 29 IFN response genes using BioMark^TMDynamic Arrays. Type I IFN bioactivity in serum of 47 IIM patients was determined using a bioassay. The role of IFNα as an interferogenic trigger was determined using neutralizing antibodies in sera of a subset of 25 patients.

Results: The IFN signature was present in 45% of IIM patients, irrespective of diagnosis. The IFN score was associated with disease activity for patients diagnosed with DM but not PM or IBM. In IIM patients with a mono-specific autoantibody profile, an association between the presence of an IFN signature and autoantibodies against RNA binding proteins, such as Jo-1, Ro60, SRP and U1RNP, was observed, whereas the absence of an IFN signature is associated with autoantibodies not directed against RNA-binding proteins, such as Ro-52, and PMScl.  Moreover, we observed an association between the presence of an IFN signature and patients with multi-specific autoantibody profiles compared to patients with a mono-specific autoantibody profiles or patients without autoantibodies (p = 0.038 and p=0.002, respectively). The IFN score correlated with type I IFN pathway-bioactivity (n=47) ( r 0.4243, p= 0.0057), which could be partly blocked by neutralizing antibodies directed against IFNα and the type I IFN receptor.

Conclusion: Overall, our findings indicate involvement of IFNα in the type I IFN activity in IIM and suggest a relationship between the presence of anti-RNA-binding protein autoantibodies and the IFN signature in IIM. This hints towards a role for RNA as trigger of type I IFN activity in IIM similarly as has been observed for SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibody-specificities-and-type-i-interferon-pathway-activation-in-idiopathic-inflammatory-myopathies/