Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates

Transpl Immunol. 2020 Jun:60:101274. doi: 10.1016/j.trim.2020.101274. Epub 2020 Mar 4.

Abstract

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established. In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions to guide DSA treatment post-transplant. Although these findings have to be confirmed in a larger prospective study, our data suggest that serum dilutions can serve as a predictive biomarker to guide peri-operative desensitization and post-transplant immunologic management.

Keywords: Antibody mediated rejection; HLA donor specific antibody; Heart transplant; High CPRA; Highly sensitized patients; Therapeutic plasma exchange.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Bronchiolitis Obliterans / diagnosis*
  • Bronchiolitis Obliterans / etiology
  • Female
  • Graft Rejection / diagnosis*
  • Graft Rejection / etiology
  • HLA Antigens / immunology
  • Heart Transplantation*
  • Humans
  • Isoantibodies / blood*
  • Middle Aged
  • Postoperative Complications / diagnosis*
  • Predictive Value of Tests
  • Prognosis
  • Serum
  • Transplant Recipients
  • Waiting Lists

Substances

  • Biomarkers
  • HLA Antigens
  • Isoantibodies