Pathogenic mechanisms and effects of treatment in chronic, idiopathic inflammatory myopathies, myositis

Myositis is a complex autoimmune disease with high morbidity and mortality. Biomarkers to predict prognosis are lacking.

Newly discovered myositis specific autoantibodies predict distinct clinical phenotypes and are promising biomarkers to identify subgroups that may share molecular pathways and prognosis.In unique patient cohorts we aim to identify prognostic biomarkers in distinct sub-groups of myositis, defined by clinical features, autoantibody profile and genetics.

We aim to identify antigen specific T and B cells and changes in muscle tissue that relate to changes in muscle strength after therapy.

Immunological and molecular methods as well as proteomics and transcriptomics will be applied.Registry data will be used to predict treatment response.

Functional, molecular studies will be focused on three sub-phenotypes of myositis patients; anti-Jo-1 positive with a high frequency of interstitial lung disease, anti-MDA5 positive with severe lung disease, anti-FHL1 positive, a muscle-specific antibody with profound muscle weakness.

Mechanisms for generation of autoantibodies and immune specificity of T and B cells will be investigated in blood, muscle and bronchoalveolar lavage fluid.

Effector function of T cells and antibodies will be investigated in cell cultures.Information on biomarkers for prognosis is highly needed to select right immunosuppressive treatment to the right patient and information on molecular pathways is important to develop new and specific therapies.