Type 1 interferons promote anti-RBC antibody responses in interferon-dependent lupus mice

Abstract Red blood cell (RBC) transfusion can induce anti-RBC antibodies that promote hemolytic events. Patients with systemic lupus erythematosus (SLE) have an increased frequency of RBC alloimmunization, and two-thirds patients express a type 1 interferon (IFNα/β) gene signature. We previously reported IFNα/β induces alloimmunization in the IFNα/β-dependent pristane mouse model. However, it is unclear whether lupus-like phenotype or directly promoted alloimmunization. Thus, we examined alloantibody responses MRL/lpr mice, which IFNα/β-independent phenotype. mice produced anti-dsDNA antibodies. unlike pristane-treated WT IFNα/β-stimulated genes (ISGs) were not elevated mice. After allogeneic RBCs, untreated minimal levels antibodies, compared to by To determine treated recombinant IFNα (rIFNα) stimulus, poly(I:C), prior transfusion. While rIFNa poly(I:C) induced they failed are resistant IFNα/β-induced due currently explored mechanism. These findings also illustrate model, but sufficient Collectively, these warrant investigation role SLE. NIH (R01 HL165169-01); (R03 HL158637-01); (K08 HL141446-03)