A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti–Jo‐1 or anti–Ro 52/anti–Ro 60 autoantibodies

Abstract

Objective. To investigate type I interferon (IFN) system activation and its correlation with autoantibodies and organ manifestations in polymyositis (PM), dermatomyositis (DM), and inclusion body myositis.Methods. Sera from 30 patients and 16 healthy controls, or purified IgG, were combined with material released from necrotized cells to stimulate Conclusion. Immune complexes containing antiJo-1 or anti-Ro 52/anti-Ro 60 autoantibodies and RNA may act as endogenous IFN␣ inducers that activate IFN␣ production in PDCs. These PDCs could be of importance for inducing myositis, whereas in DM patients without autoantibodies the presence of MX-1 protein in capillaries suggests another cellular IFN␣ source and induction mechanism. Consequently, the type I IFN system may be of importance in both PM and DM, but via different pathways.The idiopathic inflammatory myopathies polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) are characterized by symmetric, proximal muscle weakness and decreased muscle endurance. Other organs are frequently involved, such as skin in DM and lungs in PM and DM. Shared classic histopathologic features are the presence of inflammatory cell infiltrates in skeletal muscle tissue, dominated by T cells and macrophages, and regenerating and degenerating muscle fibers (1). Another characteristic feature is the presence of autoantibodies, of which anti-histidyltransfer RNA synthetase (anti-HisRS or anti-Jo-1) is one of the most frequent (2). This autoantibody is considered myositis specific and is associated with a distinctive clinical phenotype, the so-called antisynthetase syndrome, which is characterized by myositis, Raynaud's phenomenon, interstitial lung disease (ILD),

B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells

“…These findings are important, because such RNA-containing ICs mimic the endogenous inducers of IFN in SLE and other systemic autoimmune diseases with an IFN signature (3,24,25). Although PDCs and type I IFN have major effects on B cell functions (26), less is known about how B cells, beyond their autoantibody production, affect the type I IFN system and in particular PDCs.…”

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

“…The release of other cytokines and soluble mediators such as TNF and NO by the activated T and B cells may further enhance the inflammatory processes taking place in the muscle [4]. Multiple findings indicate that upregulation of the Type 1 interferon pathway plays a prominent role in the disease pathogenesis in DM [26,27]although it is not specific to DM [29].…”

Immunoregulation in Idiopathic Inflammatory Myopathies: From Dendritic Cells to Immature Regenerating Muscle Cells

“…Chemoattractive properties of autoantigenic aminoacyl-tRNA synthetases contribute to the migration and recruitment of T cells and DC. Moreover, myositis autoantibodies may act in combination with immune complexes and necrotic cells as endogenous IFN-α inducers 6 . Innate immunity.…”

“…The DC present in PM and IBM muscle are mostly mDC, in contrast to adult and juvenile DM, which had greater numbers of pDC expressing CD4 4,5 . The presence of pDC in muscle was also increased in overlap myositis associated with anti-Jo1 or anti-SSA autoantibodies 6 . An accumulation of mature DC in muscle tissue from IIM is reported in many studies 7,8 , such as the study by Gendek-Kubiak and Gendek 3 .…”