(P315) HLA-DR/DQ molecular mismatches for risk stratification and prediction of development of de novo donor-specific antibodies in cardiac allogeneic transplantation

Aim: Donor-specific antibodies (DSA) are linked to the development of antibody-mediated rejection (ABMR) in cardiac transplantation. The development of de novo (dn) class II antibodies is associated with increased mortality and poor allograft survival in cardiac transplantation. HLA-DR/DQ molecular mismatches are associated with dnDSA production in renal transplantation. However, a few studies have examined their role in cardiac transplantation. Therefore, we investigated whether HLA-DR/DQ molecular mismatches could serve as a prognostic biomarker for dnDSA(s) development in cardiac transplantation and allow recipients stratification into low, intermediate, and high alloimmune risk categories.

Method: We included 270 adult cardiac allograft recipients who underwent transplantation between January, 2007 to November, 2020. We grouped patients in high, intermediate, and low-risk categories based on single HLA-DR/DQ eplet mismatch scores: low risk with DR and DQ eplet mismatches 0-7, intermediate risk 8-15, and high risk ≥ 16. Kaplan-Meier survival analyses were used to estimate and compare allograft survival, and HLA-DR/DQ dnDSA free survival. Univariate and multivariate Cox proportional hazards models were used to calculate the hazard ratios (HR) of allograft survival, and HLA-DR/DQ dnDSA free survival.

Results: We observed that the presence of dnDSA(s) against mismatch donor HLA antigens was independently associated with ABMR in both univariate (HR = 9.55, p = <0.001), and multivariate model (HR = 7.64, p = <0.001). Although we noted a trend of increased risk with traditional HLA-A, B, and DRB1 antigen mismatches, the differences were not significant (HR = 1.22, p = 0.50). Interestingly, we found a significant association of HLA-DR/DQ single molecule eplet mismatches among high-risk group in both univariate (HR = 3.71, p = 0.016) and multivariate model (HR = 3.86, p = 0.014).

Conclusion: Our study revealed that post-transplant dnDSA(s) is an independent biomarker for diagnosis of ABMR in cardiac transplantation, and HLA eplet mismatch load could be used as a biomarker to categorize patient risk for development of dnDSA in cardiac transplantation.