The most well-known monogenic defects associated with a high risk for SLE are loss-of-function mutations in C1q and C4, encoding components of the classical complement pathway, and in the 3′-5′ exonuclease TREX1 [44, 45], the latter leading to accumulation of intracellular DNA that triggers type I IFN production. This evidence concerns the gene C4A and systemic lupus erythematosus.