The difficulty of predicting the immunological outcome of off-target pairing of either IL-12p35 or Ebi3 with other alpha/beta single IL-12 subunit proteins such as p19, p28, or p40 is also worrisome, as underscored by the recent discovery of IL-39, a novel pairing of Ebi3 and IL-23p19 that mediates pro-inflammatory responses in Lupus-like mice (34). The gene discussed is IL27; the disease is systemic lupus erythematosus.