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The type 1 interferon signature reflects multiple phenotypic and activity measures in dermatomyositis.
The type 1 interferon signature reflects multiple phenotypic and activity measures in dermatomyositis. Arthritis & rheumatology (Hoboken, N.J.) Tabata, M. M., Hodgkinson, L. M., Wu, T. T., Li, S., Huard, C., Zhao, S., Bennett, D., Johnson, J., Tierney, C., He, W., Buhlmann, J. E., Page, K. M., Johnson, K., Casciola-Rosen, L., Chung, L., Sarin, K. Y., Fiorentino, D. 2023Abstract
The type 1 interferon (IFN1) pathway is upregulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic IFN1 activity in adult patients with DM.RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed during the course of their clinical care. A previously defined 13-gene IFN1 score was modeled as a function of demographic, serologic and clinical variables using both cross-sectional and longitudinal data.The pattern of IFN1-driven transcriptional response was stereotyped across samples with a sequential modular activation pattern strikingly similar to SLE. The median IFN1 score was higher or lower in patients with anti-MDA5 or anti-Mi2 antibodies, respectively, compared to patients without these antibodies. Absolute IFN1 score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti-MDA5 antibodies. Changes in the IFN1 score over time were significantly associated with changes in skin or muscle disease activity. Stratified analysis accounting for heterogeneity in organ involvement and antibody class revealed high correlation (?=0.84-0.95) between changes in the IFN1 score and skin disease activity.The IFN1 score independently associates with both skin and muscle disease activity as well as certain clinical and serologic features in DM. Accounting for the effect of muscle disease and anti-MDA5 status reveals that the IFN1 score is strongly correlated with skin disease activity and provides support for IFN1 blockade as a therapeutic strategy for DM. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/art.42526
View details for PubMedID 37096447