Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients
| Autor: | Aditi Phadke, Lisa G. Rider, Eric P. Hoffman, Sree Rayavarapu, Kanneboyina Nagaraju, Frederick W. Miller, Svetlana Ghimbovschi |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Myeloid Plasma Cells Anti-Inflammatory Agents CD19 03 medical and health sciences 0302 clinical medicine Rheumatology immune system diseases Interferon hemic and lymphatic diseases medicine Humans Myeloid Cells Pharmacology (medical) Muscle Skeletal Myositis Aged 030203 arthritis & rheumatology B-Lymphocytes Muscle biopsy medicine.diagnostic_test biology business.industry Macrophages Skeletal muscle Middle Aged medicine.disease Basic & Translational Science 030104 developmental biology medicine.anatomical_structure Multigene Family Interferon Type I Immunology Cancer research biology.protein Biomarker (medicine) Female Rituximab Syndecan-1 business medicine.drug |
| Zdroj: | Rheumatology. 55:1673-1680 |
| ISSN: | 1462-0332 1462-0324 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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