Pathogenic mechanisms and effects of treatment in chronic rheumatic muscle inflammation, 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 molecular pathways and prognostic biomarkers in distinct sub-groups of myositis, defined by clinical features, autoantibody profile and genetics.

In a subset we aim to identify molecular changes in muscle tissue that relate to changes in muscle strength after therapy.

Immunological and molecular methods as well as proteomics and genomics will be applied.Functional, molecular studies will be focused on three sub-phenotypes of myositis patients; (i) anti-Jo-1 positive, with a high frequency of interstitial lung disease, (ii) anti-TIF1-gamma positive, associated with cancer and (iii) anti-FHL1 positive, a novel and muscle-specific antibody with profound muscle weakness.

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

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