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

• Published in: Transplant immunology 2020-06, Vol.60, p.101274-101274, Article 101274
• Main Authors: Timofeeva, Olga A., Alvarez, Rene, Pelberg, Justin, Yoon, Edward, Alsammak, Mohamed, Geier, Steve S., Ruggia-Check, Christina, Hassler, Jared, Hoosain, Jamael, Brisco, Meredith A., Afari-Armah, Nana, Rakita, Val, Brann, Stacey, Keshavamurthy, Suresh, Gomez-Abraham, Jesus, Minakata, Kenji, Toyoda, Yoshiya, Hamad, Eman
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibody mediated rejection; Biomarkers - blood; Bronchiolitis Obliterans - diagnosis; Bronchiolitis Obliterans - etiology; Female; Graft Rejection - diagnosis; Graft Rejection - etiology; Heart transplant; Heart Transplantation; High CPRA; Highly sensitized patients; HLA Antigens - immunology; HLA donor specific antibody; Humans; Isoantibodies - blood; Middle Aged; Postoperative Complications - diagnosis; Predictive Value of Tests; Prognosis; Serum; Therapeutic plasma exchange; Transplant Recipients; Waiting Lists
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2020.101274

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. •1:16 dilution of EDTA-treated sera can predict a response to 1.5 volume therapeutic plasma exchange (TPE) pre-transplant•Virtual crossmatch with 1:16 diluted serum identifies candidates for peri-operative TPE desensitization•Sera dilutions can be used as a predictive biomarker to guide DSA treatment