P.201 - Differential type I and type II interferon signatures in primary inflammatory/dysimmune myopathies

Abstract

Primary inflammatory/dysimmune myopathies (PIDM) include (i) polymyositis (PM)/inclusion body myositis (IBM), (ii) dermatomyositis (DM), (iii) necrotizing autoimmune myopathy, and (iv) overlap myositis (OM) . Type I α/β interferon signature was proposed as a characteristic feature of DM . Since OM and IBM differ from other PIDM by the presence of major histocompatibility complex (MHC)-2 expression by myofibers, we hypothesized that they are characterized by interferon (IFN)γ-mediated inflammation. To test this hypothesis, we evaluated by qPCR the expression of IFNγ, six IFNγ–induced genes (HLA-DM, -DO, -DP, -DR, CIITA, GBP2), and IFNα-induced gene ISG15 in muscle biopsy samples from patients with IBM (n = 10), DM (n = 10), NAM (n = 10), antisynthetase myositis (ASM, n = 10), and normal muscle (n = 10). Muscle IFNγ expression was found increased x50 in ASM and x80 in IBM compared to control, that of CIITA x4 and x3 (respectively) as well of HLA-DR (x5 and x8) and HLA-DM (x16 and x15). None of these genes were overexpressed in DM and NAM. ISG15 was increased x300 in DM, but not in other conditions. Our results confirmed that DM differed from other PIDM by its elective interferon α/β signature, while ASM and IBM were found associated with IFNγ signature.