(409) Virtual Desensitization with MagSort Beads Accurately Predicts Antibody Specificity Reduction in a Patient Undergoing Thoracic Organ Transplantation

Body: Desensitization therapy for highly sensitized transplant candidates faces several limitations, with expensive protocols often involving complex and demanding treatment regimens. We have previously proposed HLA-specific MagSort beads to determine the antibody specificities driving the 100% cPRA in highly sensitized renal candidates. We hypothesized this virtual desensitization protocol could similarly guide clinical practice for highly sensitized thoracic candidates by identifying specificities able to be crossed following initial versus multiple rounds of antibody-depleting therapy, allowing for optimized treatment protocols tailored to individual needs. Here, we investigate the pre- and post-transplant sera of a highly-sensitized 23-year old male (cPRA 100%) who underwent favorable desensitization with Daratumumab prior to heart transplantation to reduce titers of antibody specificities to crossable levels (Figure 1, below <5,000 MFI), significantly expanding their suitable donor pool (cPRA 94.56%). MagSort beads targeting HLA epitopes covering potential reactivity (A*25:01, A*30:01, B*07:02, B*08:01, B*15:01, C*16:01, DRB1*07:01, DQB1*04:01/DQA1*02:01, DPB1*11:01/DPA1*01:03) were used to identify the specificities present in the baseline pre-transplant sera obtained before the start of therapy (Table 1). Patient high-resolution HLA typing by GenDx NGS-Pronto Nanopore sequencing facilitated eplet analysis of the eluted specificities. SAB reactivity for longitudinal samples obtained throughout the patient’s therapeutic desensitization matched the sequential dropout of predicted epitopes from the virtual desensitization procedure with crossable levels of B71, Cw8 and Cw12 achieved by 100 days, B38 by 130 days, and DQ6, DP401 and DPA1*01 by 240 days after initiation of therapy.

Conclusion: Virtual desensitization using HLA-specific MagSort beads accurately simulated desensitization outcome based on patient-specific data in this highly sensitized thoracic candidate. Validation with a larger cohort of thoracic patients who have undergone therapeutic desensitization by Daratumumab and other therapies is needed for the virtual desensitization technique to be expanded into clinical practice. Refining the virtual desensitization protocol could lead to faster and more personalized care for highly sensitized thoracic patients.