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.
Eloranta, Maija-Leena 1; Barbasso Helmers, Sevim 2; Ulfgren, Ann-Kristin 2; Ronnblom, Lars 1; Alm, Gunnar V. 3; Lundberg, Ingrid E. 2
[Miscellaneous Article]
Arthritis & Rheumatism.
Arthritis Care & Research. 56(9):3112-3124, September 2007.
(Format: HTML, PDF)
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 (BDCA-2)-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 anti-Jo-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.
(C) 2007, American College of Rheumatology