AGS, SLE, and RNASEH2 mutations: translating insights into therapeutic advances.

Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by the presence of nucleic acid- and protein-targeting autoantibodies and an aberrant type I IFN expression signature. Aicardi-Goutières syndrome (AGS) is an autosomal-recessive encephalopathy in children that is characterized by mutations in numerous nucleic acid repair enzymes and elevated IFN levels. Phenotypically, patients with AGS and SLE share many similarities. Ribonuclease H2 (RNase H2) is a nucleic acid repair enzyme that removes unwanted ribonucleotides from DNA. In this issue of the JCI, Günther and colleagues provide an in-depth investigation of the mechanisms underlying the link between defective removal of ribonucleotides in AGS and SLE, and these findings will likely serve as a strong springboard to provide novel therapeutic inroads.