The Association of DQ Donor-Recipient Mismatching on Development of Antibody-Mediated Rejection and Donor-Specific Antibody-Positive Rejection After Pediatric Heart Transplantation.

PURPOSE: Several studies have shown lower risk of de novo donor specific antibodies (dnDSA) and antibody-mediated rejection (AMR) in adult transplant recipients with less HLA donor-recipient mismatching, particularly at the Class II DQ locus. We aimed to evaluate the association between degree of DQ antigen mismatch and risk for AMR and DSA-positive rejection development in pediatric heart transplant (HT) recipients. METHODS: Children who underwent HT from 2012 to 2023 were identified from the Pediatric Heart Transplant Society registry. Those with available DQB1 donor and recipient data obtained from merge with OPTN were included. Number of DQB1 donor-recipient mismatches (DQB1-MM) (and DQA1 for the limited subset) were determined by comparing donor and recipient HLA data. Primary outcomes evaluated were freedom from biopsy-proven AMR and freedom from DSA-positive rejection. Subset analyses were performed for those with available DQA1 data. RESULTS: A total of 3672 HT recipients were included; 1302 (35%) had 2 DQB1-MM, 1945 (53%) had 1 DQB1-MM, and 425 (12%) had 0 DQB1-MM. Those with 0 DQB1-MM were more likely to be White than those with 1 or 2 DQB1-MM (67% vs. 63% and 61%, respectively, p = 0.0268). There were no other significant differences in clinical, demographic, or transplant characteristics between the groups. There was no difference in freedom from biopsy-proven AMR based on number of DQB1-MM in either univariable or multivariable analysis. Freedom from DSA-positive rejection was significantly higher in those with 0 DQB1-MM compared to those with 1 or 2 MM (estimated 92% at 5 years posttransplant compared to 81%, p < 0.001). This association remained significant when controlling for other known rejection risk factors in multivariable analysis. CONCLUSIONS: Fewer DQ antigen mismatches are associated with improved freedom from DSA-positive rejection, but not biopsy-proven AMR in children undergoing first HT. Further study is needed to understand long-term implications of this finding and its potential use in improving posttransplant outcomes.