Nancy L Reinsmoen1, Chih-Hung Lai, James Mirocha, Kai Cao, Geraldine Ong, Mehrnoush Naim, Qi Wang, Mark Haas, Matthew Rafiei, Lawrence Czer, Jignesh Patel, Jon Kobashigawa. 1. 1 HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Biostatistics Core, Research Institute and General Clinical Research Center and Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA. 3 MD Anderson Medical Center, Houston, TX. 4 Pathology, Cedars-Sinai Medical Center, Los Angeles, CA. 5 Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA. 6 Address correspondence to: Nancy L. Reinsmoen, Ph.D., D(ABHI) HLA Laboratory, Cedars-Sinai Medical Center, 8723 Alden Dr, SSB # 197, Los Angeles, CA 90048.
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.
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.
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