Background/Purpose:

Idiopathic inflammatory myopathies (IIM) are rare autoimmune diseases characterized by the presence of autoantibodies, proximal muscle weakness and muscle inflammation. Recent studies showed an activated type I IFN activity (IFN signature)  in a subset of patients and suggest a pathogenic role for type I interferon (IFN) in IIM patients. The extent of this signature appears to be related to disease activity, however, the relevance to disease or the underlying mechanism resulting in such a signature has not been revealed yet.

The aim of this study was to examine if the type I IFN activity in whole blood and sera from IIM patients correlates to disease activity, clinical manifestations or autoantibody profile.

Methods: Clinical data were collected from 94 polymyositis, dermatomyositis and inclusion body myositis patients recruited from the Karolinska University Hospital and Prague University. Serological data was obtained using lineblot assay. RNA samples, obtained from whole blood  were assessed for expression levels of 9 IFN related genes using BioMark^TMDynamic Arrays. IFN score was determined as the average gene expression level of these genes. Median IFN score was used to define the presence of an IFN signature.  

Sera were assessed for IFN activity using a bioassay where expression of 3 type I IFN-inducible genes were quantified using real-time PCR. Two groups of patients, IFN+; IFN-, were categorized based on the sum of individual gene expression scores. Differences between these groups were assessed for clinical and serological data, as well as correlation between IFN signature and variables.

Results:

The IFN signature in peripheral blood was present in a subgroup of patients with myositis. No significant difference in the presence and extent of the IFN signature was observed between ANA negative and ANA positive patients. Comparison of the IFN signature in patients positive for myositis associated or specific autoantibodies revealed that the highest IFN score was found in U1RNP positive patients (mean IFN score = 23.66 ), followed by La positive patients (mean IFN score = 11.94) and Ro60 positive patients (..). Comparable results were found in patients with multiple autoantibody specificity and those only positive for one of these antibodies. In addition, a majority of Jo-1 and Ro-52 positive patients were characterized by the presence of an IFN signature, although most of these patients appear to be positive for multiple autoantibody specificities. Detailed analysis revealed that presence of an IFN signature was related to multi-autoantibody specificity, i.e. 17 out of 23 patients positive for 2 or more autoantibodies (70%) versus 30 out of 71 of the patients positive for 1 or none of the specific autoantibodies (45%) displayed an IFN signature (Pearson Chi square p=0.008).

Significantly more IFN+ patients were positive for ANA compared to IFN- patients (p=0.001). No correlation between IFN activity in sera and disease activity was found.

Conclusion:

These data reveal a preferential presence of the IFN signature in IIM patients that are characterized by multiple autoantibody specificities. These findings suggest a role for autoantibodies in the induction of type I IFN activity in IIM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ifn-signature-is-associated-with-autoantibody-profiles-in-patients-with-idiopathic-inflammatory-myopathies/