1. Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates
- Author
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Nana Afari-Armah, Mohamed Alsammak, Stacey Brann, Meredith A. Brisco, Suresh Keshavamurthy, Olga A. Timofeeva, J. Gomez-Abraham, Christina Ruggia-Check, Justin Pelberg, J. Hoosain, Jared Hassler, Eman Hamad, Steve S. Geier, Yoshiya Toyoda, Val Rakita, Kenji Minakata, Edward J. Yoon, and Rene Alvarez
- Subjects
Adult ,Graft Rejection ,Serum ,Oncology ,medicine.medical_specialty ,Waiting Lists ,Serial dilution ,medicine.medical_treatment ,Immunology ,Postoperative Complications ,HLA Antigens ,Isoantibodies ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Prospective cohort study ,Bronchiolitis Obliterans ,Aged ,Desensitization (medicine) ,Predictive biomarker ,Transplantation ,biology ,business.industry ,Perioperative ,Middle Aged ,Prognosis ,medicine.disease ,Transplant Recipients ,Heart failure ,biology.protein ,Heart Transplantation ,Female ,Antibody ,business ,Biomarkers - 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.
- Published
- 2020