Abstract: SA-OR80
Risk HLA-DQ Heterodimer Mismatch Is Associated with De Novo Donor-Specific Antibodies in Pediatric Kidney Transplant Recipients
Session Information
- Pediatric Nephrology: Insights and Innovations
October 26, 2024 | Location: Room 23, Convention Center
Abstract Time: 05:40 PM - 05:50 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Sigurjonsdottir, Vaka, University of Miami Miller School of Medicine, Miami, Florida, United States
- Piburn, Kim H., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Wang, Lin, Stanford University, Stanford, California, United States
- Turudic, Daniel, University Hospital Centre Zagreb, Zagreb, Croatia
- Grimm, Paul C., Stanford University, Stanford, California, United States
- Tambur, Anat R., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Zhang, Bing M., Stanford University, Stanford, California, United States
Background
Recently, the role of HLA-DQα/β heterodimer mismatches in transplantation was recognized, suggesting that heterodimers including the DQα05 chain as part of the mismatched donor allele, carry a higher risk of developing de-novo donor-specific antibodies (dnDSA).
Methods
Children who underwent kidney transplantation from 1/1/2010-3/1/2018 at Stanford Children's Health, with ≥12-month follow-up, were included and followed through 9/1/2022. DQα/β heterodimers were paired based on linkage disequilibrium with HLA-DRB1 and mismatches were determined at the level of the heterodimers. A risk mismatch was defined as the presence of DQα05 heterodimer in the donor, not the recipient. Outcome of interest was development of dnDSA to HLA-DQ, defined when detected mean fluorescence intensity (MFI) was ≥ 1000. All patients were tested for dnDSA at 0, 1, 2-, 3-, 6-, and 12 months following transplant, at least annually after that, and as clinically indicated. Survival analysis was performed by the Kaplan-Meier method and odds ratios were used to compare the relative odds.
Results
A total of 227 patients were included. The median age was 13 (IQR 9), 24% had living donor transplant and 49% were female. The median follow-up time was 68 months (IQR 40). 87 (38%) formed dnDSA against HLA-DQ. 77/227 (34%) had a DQα05-heterodimer mismatch, of those 43/77 (56%) formed dnDSA, vs. 44/150 (29%) Figure. The table shows frequency of heterodimers and dnDSA formation.
Conclusion
DQα05 heterodimer mismatch was highly associated with the formation of HLA- dnDSA in our cohort. Identification of immunogenic DQ mismatches may help optimize allocation systems, guide the selection of organs for sensitized patients, and immunologic risk stratification post-transplant to improve graft outcomes.