Pre-transplant ATR 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 (ATR-Ab) as a risk factor for rejection and kidney graft loss. This study sought to validate the risk of ATR-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 ATR-Ab and other non-HLA Ab using a commercially available ELISA kit and the Luminex platform, respectively. Patients positive for pre-transplant ATR-Ab were more likely to develop de novo donor-specific Ab (dnDSA) compared to patients that were negative for ATR-Ab (28% vs 10%, p=0.027). Pre-transplant positivity for ATR-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). ATR-Ab positivity was significantly associated with positivity for Ab against the endothelin A type 1 receptor (ETR-Ab) inclusive of all study time points (p=0.0021). Given the high prevalence of ATR-Ab pre-transplant (20%) and its association with dnDSA and early TCMR, a prospective study to determine if more intense immunosuppression and/or ATR blockade has an impact on outcomes in these patients is warranted.