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

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 IFN alpha production by peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Muscle biopsy specimens from 25 patients and 7 healthy controls were investigated for blood dendritic cell antigen 2 (BDCA2)-positive plasmacytoid dendritic cells (PDCs) and IFN alpha/beta-inducible myxovirus resistance 1 (MX-1) protein. Results. Sera from 13 patients who were positive for anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies induced IFN alpha production in PBMCs when combined with necrotic cell material. In addition, IgG prepared from anti-jo-1-positive PM sera induced IFN alpha with necrotic material, but not when the latter was treated with RNase. BDCA-2 expression in PDCs in muscle tissue was increased in PM patients with anti-Jo-1 autoantibodies, while MX-1 staining in capillaries was increased in DM patients, compared with healthy individuals. IFN alpha-inducing capacity correlated with interstitial lung disease, while MX-1 expression in the capillaries correlated with DM. Conclusion. Immune complexes containing antiJo-1 or anti-Ro 52/anti-Ro 60 autoantibodies and RNA may act as endogenous IFN alpha inducers that activate IFN alpha 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 alpha source and induction mechanism. Consequently, the type I IFN system may be of importance in both PM and DM, but via different pathways.