Allosensitization in Heart Transplantation: The Importance of a Comprehensive Approach

Introduction HLA sensitization presents a major barrier to transplantation yet sensitive techniques such as the Luminex Single Antigen Bead (SAB) assay, when used in isolation, may inappropriately limit the donor pool. We report a case of apparent robust HLA sensitization following HBV vaccination and describe our approach to the assessment of HLA reactivity leading to successful heart transplantation (HTx). Case Report A 50 year old Caucasian male with long standing ARVD developed recurrent VT and worsening RV dysfunction leading to HTx evaluation. There was no history of transfusion, surgery, or mechanical circulatory support. The Luminex SAB assay at listing and serially thereafter was negative. Unexpectedly, broad class II HLA sensitization (cPRA 98%) was suddenly detected by SAB assay after HBV vaccination concerning for either a heterologous immune response or false reactivity to the beads. Multiple antibodies (Abs) persisted at 1:8 dilution and included Abs against the recipients own HLA (autologous flow XM negative). At the time when a donor became available, 4 DSA were identified on the most recent Luminex SAB. Given his high cPRA in the absence of a strong allosensitizing event, we combined assessment with an alternative solid phase assay (LABScreen PRA), 4-digit donor typing, and prospective crossmatches by Flow Cytometry (FC) and Complement Dependent Cytotoxicity (CDC) to determine the safety of proceeding with HTx (Figure 1). Notably, no HLA Abs were detected using the LABScreen PRA and both FC and CDC crossmatches were negative. The patient underwent successful HTx with no rejection and normal graft function. Summary HLA allosensitization portends worse outcomes after transplant. However, the high sensitivity of the Luminex SAB and potential for false positivity may result in inappropriately limiting access to HTx. This case highlights the importance of comprehensive assessment of HLA sensitization in situations of uncertainty to help identify pathogenic HLA Abs and allow for successful HTx.