Pre-transplant AT₁R antibodies correlate with early allograft rejection

Studies investigating the potential pathogenic effects of non-HLA antibodies (Ab) have identified Ab against the angiotensin II type 1 receptor (AT₁R-Ab) as a risk factor for rejection and kidney graft loss. This study sought to validate the risk of AT₁R-Ab for acute rejection and to explore the role of other non-HLA Abs in this capacity. Pre- and post-transplant sera from a cohort of 101 patients (n = 453 samples total) were tested for AT₁R-Ab and other non-HLA Ab using a commercially available ELISA kit and the Luminex platform, respectively. Patients positive for pre-transplant AT₁R-Ab were more likely to develop de novo donor-specific Ab (dnDSA) compared to patients that were negative for AT₁R-Ab (28% vs 10%, p = 0.027). Pre-transplant positivity for AT₁R-Ab was associated with TCMR in the first year post-transplant (p = 0.034), but did not predict graft loss independent of dnDSA (p = 0.063). AT₁R-Ab positivity was significantly associated with positivity for Ab against the endothelin A type 1 receptor (ET_AR-Ab) inclusive of all study time points (p = 0.0021). Given the high prevalence of AT₁R-Ab pre-transplant (20%) and its association with dnDSA and early TCMR, a prospective study to determine if more intense immunosuppression and/or AT₁R blockade has an impact on outcomes in these patients is warranted.