P149 Anti-angiotensin ii type 1 receptor antibodies are associated with positive flow crossmatches in heart Transplant Candidates

Abstract

Aim Heart transplant (HTX) candidates with pre-formed anti-HLA antibody (HLA-Ab) have lower transplantation rates and increased waiting time due to positive crossmatches. Anti-angiotensin II type 1 receptor antibody (AT1R-Ab) has recently been associated with allograft loss and antibody-mediated rejection. The aim of the present study was to evaluate: 1) the prevalence of anti-angiotensin receptor 1 antibody (AT1R-Ab) in HTX candidates and 2) the impact of AT1R-Ab on flow cytometry crossmatch (FXM). Methods 115 HTX candidates were tested by ELISA for the presence of AT1R-Ab (U/mL after 1:50 dilution, positive cut-off = 10 U/mL, strong-positive cut-off = 20 U/mL. 43/115 cases were identified with either positive (N = 15) or negative (N = 28) flow crossmatches in the absence of any donor-specific anti-HLA alloantibody (virtual negative crossmatches for HLA antibody). Mean channel shift (MCS) for flow cytometry crossmatches was measured on a 1024 scale. Finally, two index HTX cases with pre-formed AT1R-Ab and positive flow crossmatches are discussed. Results A high proportion of HTX candidates with HLA-Ab exhibited AT1R-Ab (Strongly reactive AT1R-Ab 46/115, 40%; weakly reactive AT1R-Ab 25/115, 21.7%; no AT1R-Ab 44/115, 38.2%). Furthermore, AT1R-Ab levels were significantly higher in patients with a positive versus a negative flow crossmatch (54.81  ±  54.92 versus 9.04  ±  7.36, p = 0.00001, Fig. 1). In addition, MCS was significantly higher in patients with AT1R-Ab versus patients without antibodies (73.95  ±  94.21 versus −51.45  ±  52.07, p = 000003, Fig. 2). In the 15 cases with positive flow crossmatch without HLA-specific antibody, all 15 patients exhibited AT1R-Ab, 11/15 had strong AT1R-Ab, while only 5/25 patients with negative FXM exhibited AT1R-Ab, Chi-square = 24, p = 0.00001). Conclusions More than half of HTX candidates exhibit AT1R-Ab, which can interfere with flow crossmatch interpretation even in the absence of HLA-specific antibodies.