P026Timing is everything – Even for DP antibodies

Abstract

Introduction Donor Specific Antibodies (DSA) can be a contraindication for kidney transplants. The clinical relevance of DSA to DP antigens and correlation with crossmatch (XM) remain unclear. We report the conversion of a negative XM to positive due to development of DSA to DP6, most likely caused by an unreported sensitizing event. Methods A 38 yo female received a deceased donor (DD) kidney transplant (Tx) after negative T/B cell flow XMs using sera drawn 35 and 44 days pre Tx (day −35 and −44). Delta channel shifts (DCS) in these XMs were: T = 0 for both sera; B = 37 and 31 for days −35 and −44. These sera were negative for DSA. We received a serum drawn at admission for Tx (day −1). The patient received blood transfusions within the previous week (day −6). The day-1 serum had high level DSA to DP6 (MFI = 13,723), compared to day −44 (1,321) and day-35 (1,653). By flow XM, the day −1 serum was T negative, B positive (DCS = 228), likely due to the increase in DSA to DP6. In addition to standard immunosuppression, this recipient also received thymoglobulin and basiliximab once the program was notified of high level DSA and positive flow XM. Post Tx monitoring showed an immediate decline in DSA to DP6: post Tx day 6 (MFI = 7,380), day 12 (5,669), day 21 (4,042), day 63 (485). The DSA to DP6 remained low (MFI 400) for five years. However, the recipient had BK viremia and a kidney biopsy five years post Tx showed “arteriolar hyalinosis and arteriosclerosis related to possible CNI toxicity”. The recipient is re-listed in UNET for another kidney Tx, the primary reason for graft failure deemed transplant glomerulopathy. Discussion This case emphasizes the importance of timely antibody testing in relation to XM testing, awareness of sensitizing events, and updated HLA typing. Our lab now employs stricter guidelines to ensure more frequent receipt of patient sera, especially following potential sensitizing events. At the time of this patient’s Tx, DP typing was not performed on DD. After discovering the increase in antibodies at pre Tx day −1, but absence of DSA, we performed DP typing. Finding DP6 as a DD antigen helped explain the change to positive XM, as the level of DSA to DP6 significantly increased following the sensitizing event pre-Tx. This early peri and post Tx antibody response may have contributed to reduced graft survival and transplant glomerulopathy.