Anti-MDA5 autoantibodies in idiopathic inflammatory myopathies: studies on MDA5 reactivity

Idiopathic Inflammatory Myopathies (IIM) are a group of rare systemic autoimmune diseases, for which the origin and molecular pathogenesis are unresolved and available therapies are insufficient. For unknown reasons, patients suffer from inflammation-driven tissue damage in the muscle, skin and lung and the overactivated immune system produces antibodies against endogenous proteins. The association of distinct clinical manifestations with the presence of a certain autoantibody suggests the autoantibodies play a detrimental role at the molecular level in the development of disease. We will focus on two autoantibodies, anti-MDA5 and anti-Jo1, that are associated with the incidence of lung disease, a clinical manifestation that causes high morbidity and mortality in myositis patients. However, due to a lack of representative in vitro and in vivo models, the precise role of autoantibodies in the molecular pathogenesis is unknown. In an attempt to bridge the gap and generate representative in vitro models, we aim to isolate and produce autoantibodies from patient material so they can be harnessed as laboratory tools for in vitro studies. Understanding the role of these autoantibodies in the molecular pathways leading to pathology will lead to more disease insight and the identification of new, potentially druggable, targets.