Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies

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• 作者：L. Ekholm ; S. Vosslamber ; A. Tjrnlund ; T. D. de Jong ; Z. Betteridge ; N. McHugh ; L. Plestilova ; M. Klein ; L. Padyukov ; A. E. Voskuyl ; I. E. M. Bultink ; D. Michiel Pegtel ; C. P. Mavragani ; M. K. Crow ; J. Vencovsky ; I. E. Lundberg and C. L. Verweij
• 刊名：Scandinavian Journal of Immunology
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：84
• 期：2
• 页码：100-109
• 全文大小：400K
• ISSN：1365-3083

文摘

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.