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

Kwun, J

Page, E

Hong, JJ

Gibby, A

Yoon, J

Farris, AB

Villinger, F

Knechtle, S

United States

2015-05-14T18:34:33Z

2015-03

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.

http://www.ncbi.nlm.nih.gov/pubmed/25675879

1600-6143

https://hdl.handle.net/10161/10054

eng

Elsevier BV

Am J Transplant

10.1111/ajt.13045

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

Animals

Antibodies, Neutralizing

Antibody Formation

B-Cell Activating Factor

Graft Survival

Humans

Kidney Transplantation

Lymphocyte Depletion

Macaca mulatta

Male

Models, Animal

Recombinant Fusion Proteins

T-Lymphocytes

Tumor Necrosis Factor Ligand Superfamily Member 13

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

Journal article

Kwun, J|0000-0002-8563-5472

Knechtle, S|0000-0002-1625-385X

http://www.ncbi.nlm.nih.gov/pubmed/25675879

815

822

3

Clinical Science Departments

Duke

Duke Clinical Research Institute

Institutes and Centers

School of Medicine

Surgery

Surgery, Abdominal Transplant Surgery

Published

15