Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model

Am J Transplant. 2015 Mar;15(3):815-22. doi: 10.1111/ajt.13045. Epub 2015 Feb 12.


Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increased serum B cell activating factor/survival factor (BAFF) with increased risk of antibody-mediated rejection in alemtuzumab treated patients. In the present study, we tested the ability of BAFF blockade (TACI-Ig) in a nonhuman primate AMR model to prevent alloantibody production and prolong allograft survival. Three animals received the AMR inducing regimen (CD3-IT/alefacept/tacrolimus) with TACI-Ig (atacicept), compared to five control animals treated with the AMR inducing regimen only. TACI-Ig treatment lead to decreased levels of DSA in treated animals at 2 and 4 weeks posttransplantation (p < 0.05). In addition, peripheral B cell numbers were significantly lower at 6 weeks posttransplantation. However, it provided only a marginal increase in graft survival (59 ± 22 vs. 102 ± 47 days; p = 0.11). Histological analysis revealed a substantial reduction in findings typically associated with humoral rejection with atacicept treatment. More T cell rejection findings were observed with increased graft T cell infiltration in atacicept treatment, likely secondary to the graft prolongation. We show that BAFF/APRIL blockade using concomitant TACI-Ig treatment reduced the humoral portion of rejection in our depletion-induced preclinical AMR model.

Keywords: B cell biology; alloantibody; animal models: nonhuman primate; basic (laboratory) research/science; immunosuppression/immune modulation; kidney transplantation/nephrology; rejection: antibody-mediated (ABMR); translational research/science.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibody Formation
  • B-Cell Activating Factor / immunology*
  • Graft Survival
  • Humans
  • Kidney Transplantation*
  • Lymphocyte Depletion*
  • Macaca mulatta
  • Male
  • Models, Animal*
  • Recombinant Fusion Proteins / therapeutic use*
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology*


  • Antibodies, Neutralizing
  • B-Cell Activating Factor
  • Recombinant Fusion Proteins
  • TNFSF13B protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • TACI receptor-IgG Fc fragment fusion protein