The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients

• Authors: Ronald Parsons, Emory University; Arslan Zahid, Emory University; Shalini Bumb, Emory University; Hannah Decker, Emory University; Harold Sullivan, Emory University; Frances Lee, Emory University; Idelberto Badell, Emory University; Mandy Ford, Emory University; Christian Larsen, Emory University; Thomas Pearson, Emory University; Annette M. Jackson, Duke University; Dong-Feng Chen, Duke University; Matthew Levine, University of Pennsylvania; Malek Kamoun, University of Pennsylvania; Robert Bray, Emory University; Howard Gebel, Emory University
• Journal Title: American Journal of Transplantation
• Volume: Volume 20, Number 2
• Publisher: Wiley | 2019-10-08, Pages 573-581
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/ajt.15585
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Pathology; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Surgery; Transplantation; alloantibody; clinical research; practice; immunosuppressant - fusion proteins and monoclonal antibodies; belatacept; immunosuppression; immune modulation; kidney transplantation; nephrology; sensitization; Costimulation blockade; Renal transplantation; Allocation system; Antibody; Desensitization; Responses; Cells; KAS

Abstract

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P <.0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P <.01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.