Document Type
Journal Article
Publication Date
9-2016
Journal
Rheumatology
Volume
55
Issue
9
Inclusive Pages
1673-1680
DOI
10.1093/rheumatology/kew213
Abstract
Objective. To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM.
Methods. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks.
Results. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19 + B cells and CD68 + macrophages in responders.
Conclusion. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity.
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APA Citation
Nagaraju, K., Ghimbovschi, S., Rayavarapu, S., Phadke, A., Rider, L. G., Hoffman, E. P., & Miller, F. (2016). Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.. Rheumatology, 55 (9). http://dx.doi.org/10.1093/rheumatology/kew213
Peer Reviewed
1
Open Access
1
Comments
Copyright Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.