Are All DSA’s the Same? Are We Ready for Precision Medicine in Pediatric LT?
1Georgetown University School of Medicine, Washington, DC, 2Medstar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, 3Biostatistics, Bioinformatics, & Biomathematics, Georgetown University, Washington, DC, 4Histocompatibility Laboratory, Dept. of Pathology & Laboratory Medicine, Georgetown University, Washington, DC
Meeting: 2021 American Transplant Congress
Abstract number: 294
Keywords: Histocompatibility, HLA antibodies, Liver transplantation, Pediatric
Topic: Clinical Science » Liver » Liver: Pediatrics
Session Information
Session Time: 6:00pm-7:00pm
Presentation Time: 6:25pm-6:30pm
Location: Virtual
*Purpose: Donor-specific antibodies (DSA) play an uncertain role in rejection after liver transplantation (LT). We hypothesized that evaluation of epitope differences in HLA-DR/DQ mismatching can improve identification of alloimmune sensitization risk.
*Methods: Retrospective review of pediatric LTs performed in our center between January 2003 and November 2019 with at least 1 DSA measurement using Luminex® Single Antigen bead platform (positive cutoff 1000 MFI). HLAMatchmaker™ 3.1 was used to determine the number of mismatched DRB1/DQB1 eplets for each donor-recipient pair. ROC analysis was used to identify optimal cutoff of eplet mismatch load for de novo DSA (dnDSA). Chi-squared tests and ANOVA were used to compare demographic and clinical parameters including development of dnDSA & acute rejection (AR) across the three risk groups. Log-rank tests & Cox proportional were used to evaluate the association between the three risk groups & dnDSA-free survival, & AR.
*Results: Out of 244 pediatric LT, DSA testing in 172 detected dnDSA in 73 (42%). ROC determined an eplet mismatch load of 6 & 2 for antibody-verified DRB1 & DQB1 dnDSA (AbDRB / AbDQB), respectively, with AUC of 0.68 & 0.60 respectively. High-risk patients had significant shorter dnDSA-free survival vs. low risk patients (log-rank p < 0.01) (Figure 1A). There was no significant age, or race difference in dnDSA-free survival, and anti-DQ2 did not predominate (Figure 1B). AR frequency was 19%. AR-free survival did not differ between high-risk vs. low-risk patients with Ab-verified dnDSA (log-rank p = 0.05) or between DSA pos vs. DSA neg patients.
*Conclusions: Mismatched epitope load can predict DSA-free survival in pediatric LT recipients. Although previous reports found that DQ2 dnDSA was associated with an increased likelihood of AR, we found no significant association, possibly due in part to low frequency using eplet mismatch methodology.
To cite this abstract in AMA style:
Shin SE, Lee M, Yazigi N, Khan K, Kaufman S, Ahn J, Timofeeva O, Ekong U. Are All DSA’s the Same? Are We Ready for Precision Medicine in Pediatric LT? [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/are-all-dsas-the-same-are-we-ready-for-precision-medicine-in-pediatric-lt/. Accessed December 12, 2024.« Back to 2021 American Transplant Congress