1st Saudi Transplant Congress 2025, Riyadh, Saudi Arabia, April 29-May 1, 2025: Abstracts

Introduction: Formation of de novo donor-specific antibodies (dn-DSA) is a major long-term immunological complication after liver transplantation (LT).We hypothesized that the mismatch of HLA class II epitopes/eplets is a marker of immunogenicity and a risk factor for the formation of dn-DSA.Materials and Methods: Sera from 80 liver recipients were prospectively examined for the presence of dn-DSA using Luminex-LabScan 3D single antigen solid-phase analysis (One Lambda, Inc., Canoga Park, CA USA) 1, 2, 3, 6, 12, 18, 24, and 36 months after LT.HLA typing of the recipients and donors were performed using PCR-SSP and -SSOP medium resolution methods.The cross-match was performed by flow fluorometry (FCM).The HLAMatchmaker computer algorithm was used to identify incompatible epitopes/eplets of the HLA-DRB1 and -DQA1/B1 loci.Standard immunosuppression included thymoglobulin-Rituximab induction and tacrolimus maintenance therapy.Result: In 27 (34%) recipients, the formation of dn-DSA was noted after a median of 165 (9-906) days after LT.We did not observe episodes of humoral rejection in this group of patients, while nine recipients (11%) developed acute cellular rejection (ACR).Positive FCM and a greater numbers of incompatible HLA-A, -B, -DR were not associated with the formation of dn-DSA (P>0.05).However, recipients who developed dn-DSA had significantly greater numbers (38.0 2.7 vs. 28.0 2.3; P = 0.01) of antibody-confirmed (14.0 1.1 vs. 10.0 1; P = 0.015) incompatible HLA class II epitopes/eplets.The number of incompatible class II epitopes/eplets was associated with the risk of class II dn-DSA formation, in most cases against HLA-DQ (OR=1.2;P < 0.01).In patients with ACR, a significantly higher number of common (20.2 1.3 versus 13.9 0.9; P < 0.01), as well as antibodyconfirmed (10.7 1.1 versus 7.5 0.6; P = 0.03) Class I incompatible HLA epitopes were detected.Conclusions: We found that the risk of dn-DSA and ACR formation in LT recipients is associated not with the degree of HLA incompatibility, but with the number of incompatible epitopes/eplets, both common and those whose existence is confirmed by antibodies.Further studies are needed for a more in-depth analysis of incompatible epitopes, including the degree of their immunogenicity, as well as their use in organ distribution.