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Transplantation:
doi: 10.1097/01.TP.0000436927.08026.a8
Clinical and Translational Research

Increased Negative Impact of Donor HLA-Specific Together With Non-HLA–Specific Antibodies on Graft Outcome

Reinsmoen, Nancy L.1,6; Lai, Chih-Hung1; Mirocha, James2; Cao, Kai3; Ong, Geraldine1; Naim, Mehrnoush1; Wang, Qi1; Haas, Mark4; Rafiei, Matthew5; Czer, Lawrence5; Patel, Jignesh5; Kobashigawa, Jon5

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Abstract

Background

De novo donor HLA-specific (dnDSA) and non-HLA antibodies including antiangiotensin type 1 receptor antibodies (AT1R-abs) have been associated with antibody-mediated rejection (AMR) and decreased graft survival as well as cellular-mediated rejection (CMR) and early onset of microvasculopathy in heart transplantation. The aim of our study was to determine the impact of anti–AT1R-ab and anti–donor HLA–specific antibody (DSA) on clinical outcomes.

Methods

Pretransplant and posttransplant sera from 200 recipients transplanted between May 2007 and August 2011 were tested for DSA (Luminex-based single antigen bead assay) and AT1R-ab (enzyme-linked immunosorbent assay). Two cutoff levels (≥17 and ≥12 units) were used to define high and intermediate binding of AT1R-ab. Clinical parameters examined were 5-year AMR/CMR (≥grade 2), coronary artery vasculopathy, and survival.

Results

At 2 years after transplant, freedom from AMR and/or CMR was 95.4% for those with no DSA (n=175), 66.9% for those with dnDSA (n=19), and 25% for those with DSA at transplant (n=6) (P<0.0001). Neither ≥17 nor ≥12 units of pretransplant levels indicated a significant difference in freedom from AMR and/or CMR. When both dnDSA and AT1R-ab ≥17 or ≥12 units were considered, freedom from AMR and/or CMR decreased to 50% and 45% (P<0.0001), respectively. Coronary artery vasculopathy and survival were not significantly impacted.

Conclusions

These results show the increased negative impact of dnDSA and AT1R-ab on freedom from AMR and/or CMR and an increased hazard ratio when both parameters are considered. Both HLA- and non-HLA–specific antibodies seem to impact graft outcome in heart transplantation.

Copyright © 2014 by Lippincott Williams & Wilkins

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