Increased Negative Impact of Anti-Angiotensin Type 1 Receptor Antibodies Together with De Novo Donor HLA Specific Antibodies on Graft Outcome in Heart Transplant Recipients

Purpose De novo donor HLA specific antibodies (dnDSA) and non-HLA antibodies (abs) including anti Angiotensin Type 1 receptor (AT 1 R) abs have been associated with ab mediated rejection (AMR) and decreased graft survival in solid organ recipients (recips). In renal recips high levels of anti-AT 1 R have been associated with AMR in the absence of DSA and C4d deposition. We examined the impact of dnDSA and anti-AT 1 R abs on graft outcome including AMR, cellular mediated rejection (CMR), coronary artery vasculopathy (CAV), and survival. Methods and Materials Pre and post transplant (tx) sera from 200 heart recips txed between May 2007 and August 2011 were tested for DSA (Luminex Single Antigen Beads) and anti-AT 1 R (ELISA) with high levels being defined as >=17units. The clinical outcome parameters examined were: 5 yr AMR/CMR (>=grade2), CAV, and survival. Results 20 recips (10%) developed dnDSA: 3 cl I only, 5 cl I and II; 12 cl II only (predominantly DQ). 76 recips had pretx AT 1 R >=17 units (HI-AT 1 R) and 155 recips AT 1 R 1 R group. Importantly, 5 recips with AMR+/or CMR had HI-AT 1 R levels and no dnDSA. dnDSA+ recips tended to have lower survival (P=0.097) and significantly lower freedom from AMR (P 1 R and dnDSA. The hazard ratio for AMR/CMR at 5 yrs. was 5.8 for dnDSA+ (P 1 R, and increased to 8.1 when both dnDSA and HI-AT 1 R were considered (P= Conclusions HI-AT 1 R may account for the AMR +/or CMR diagnoses without concomitant dnDSA. The presence of both HI-AT 1 R and dnDSA resulted in the lowest freedom from AMR/CMR emphasizing the importance of both HLA & non-HLA specific abs in the immune response to organ tx.