Multiple potential mechanisms for anti-MDA5 antibody production have been proposed: individuals with specific genetic backgrounds (such as HLA-DRB1*04:01, *04:05, *12:02, *12:01 (67–70) and WDFY4 variants (71–73)) may exhibit constitutive activation of the RNA-MDA5 signalling pathway even in the absence of known viral infections, leading to robust induction of IFN-I. This evidence concerns the gene IFIH1 and viral infectious disease.