A missense mutation in <i>IFIH1</i> encoding a cytoplasmic viral RNA sensor MDA5 has recently been identified in the SMS patients as well as in patients with a monogenic form of lupus.
This longitudinal study focused on the relationship between lupus activity and the levels of intracellular proteins, phosphorylated interferon regulatory factor 7 (pIRF7), caspase-9 and -10, and mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated protein 5 (MDA5).
Association between each of 135 genotyped SNPs in IFIH1 and four lupus-associated plasma mediators, IL-6, TNF-α, IFN-β, and IP-10, were investigated via linear regression.
This finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in IFIH1 (ranging from inflammatory encephalopathy to prototypic systemic autoimmune disease).