designed a human fusion recombinant protein (Hybri) with two domains: CTLA-4 (to block the CD28-CD80 costimulatory pathway) and PD-L2 (to exacerbate the PD-1-PD-L2 coinhibitory pathway); this protein prevented the progression of proteinuria and anti-dsDNA to levels similar to those of cyclophosphamide, as well as reduced the histological score, infiltration of B and T cells and macrophages, and immune deposition, in NZB/WF1 and MRL/lpr mouse models of lupus nephritis (Table 1) (111). This evidence concerns the gene PDCD1 and lupus nephritis.