title: Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.
abstract: To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center Department of Integrative Systems Biology, Institute for Biomedical Sciences, George Washington University, Washington, DC.
authors.forename: Kanneboyina
authors.initials: K
authors.lastname: Nagaraju
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ghimbovschi
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center Department of Integrative Systems Biology, Institute for Biomedical Sciences, George Washington University, Washington, DC.
authors.forename: Sree
authors.initials: S
authors.lastname: Rayavarapu
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center.
authors.forename: Aditi
authors.initials: A
authors.lastname: Phadke
authors.affiliation: Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Rider
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center Department of Integrative Systems Biology, Institute for Biomedical Sciences, George Washington University, Washington, DC.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA millerf@mail.nih.gov.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000502:physiology; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism; D009220:Myositis / Q000188:drug therapy* / Q000235:genetics; D010950:Plasma Cells / Q000378:metabolism; D000069283:Rituximab / Q000627:therapeutic use*; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007370:Interferon Type I; D053668:Syndecan-1; D000069283:Rituximab
keywords: IFN signature; biomarker; myositis; rituximab