Fig. 3.

Proposed pathogenesis of anti-MDA5 DM. In individuals with a particular genetic factors (HLA or non-HLA), an unknown viral trigger can lead to sensing of the viral double stranded Ribonucleic Acid (dsRNA) by cytoplasmic Pattern Recognition Receptors (PRR) like Melanoma Differentiation-Associated gene 5 (MDA5)/Retinoic Acid Inducible Gene-1 (RIG-1). This in turn results in activation of mitochondrial antiviral signaling protein (MAVS) which in conjugation with TNF Receptor associated factors (TRAF) recruits Tank binding kinase-1 (TBK-1) and IBK kinase (IKK). These then result in phosphorylation and activation of transcription factors-Interferon Regulatory factors (IRF) 3 and 7. These translocate into the nucleus and trigger type-1 interferon production. Virus induced cell injury and lysis, may result in release of viral-MDA5 complexes/MDA5. These complexes can be recognized by antigen presenting cells (APCs) and with a subsequent activation of helper T cells and B cells, production of autoantibody against MDA5. Activated cells and autoantibodies enter the systemic circulation and encounter autoantigens resulting in a systemic autoimmune response