TY - JOUR
T1 - Serum dilutions as a predictive biomarker for peri-operative desensitization
T2 - An exploratory approach to transplanting sensitized heart candidates
AU - Timofeeva, Olga A.
AU - Alvarez, Rene
AU - Pelberg, Justin
AU - Yoon, Edward
AU - Alsammak, Mohamed
AU - Geier, Steve S.
AU - Ruggia-Check, Christina
AU - Hassler, Jared
AU - Hoosain, Jamael
AU - Brisco, Meredith A.
AU - Afari-Armah, Nana
AU - Rakita, Val
AU - Brann, Stacey
AU - Keshavamurthy, Suresh
AU - Gomez-Abraham, Jesus
AU - Minakata, Kenji
AU - Toyoda, Yoshiya
AU - Hamad, Eman
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Antibody mediated rejection
KW - HLA donor specific antibody
KW - Heart transplant
KW - High CPRA
KW - Highly sensitized patients
KW - Therapeutic plasma exchange
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U2 - 10.1016/j.trim.2020.101274
DO - 10.1016/j.trim.2020.101274
M3 - Article
C2 - 32142756
AN - SCOPUS:85081607833
SN - 0966-3274
VL - 60
JO - Transplant Immunology
JF - Transplant Immunology
M1 - 101274
ER -