Prevalence and Dynamics of HLA donor-specific antibodies in simultaneous liver-kidney transplantation

Donor-specific antibodies (DSAs) negatively affect outcomes in solid organ transplantation outcomes, but their significance in simultaneous liver-kidney (SLK) transplant recipients remains incompletely understood. This study investigates the prevalence, dynamics, and clinical impact of both preformed and posttransplant DSAs in patients undergoing SLK transplantation.

A retrospective cohort of 151 SLK recipients transplanted at UCLA from 2014 to 2024 was analyzed. Assessment of DSA status, DSA strength (mean fluorescence intensity (MFI), and clinical outcomes including rejection and patient survival were performed. Patient survival was analyzed using Kaplan-Meier survival curves.

Of the 151 patients, 35 (23.2 %) were transplanted with preformed DSAs. Among 110 patients with posttransplant DSA testing, 25 (22.7 %) developed new DSAs, with a significantly higher incidence in females (37.8 % vs. 15.1 %, p = 0.014). Preformed DSAs were not significantly associated with rejection in kidney, liver, or combined allografts. However, posttransplant DSAs correlated with increased rejection risk: 3/25 (12 %) vs. 1/85 (1.2 %) in kidney (p < 0.05) alone and 12 % vs. 8.2 % in liver (p < 0.05) alone. Four patients experienced antibody-mediated rejection, and all four patients had either preformed or posttransplant de novo DSA. Preformed Class II DSAs were more persistent posttransplant and were more frequently associated with rejection (p < 0.05). Both preformed and posttransplant DSAs significantly declined over time posttransplant, although class II DSAs exhibited more resistance to clearance compared to class I DSA. Survival analysis revealed no statistically significant differences among patients without DSA, preformed DSA and posttransplant DSA groups; however, patients without DSAs had the highest 5-year survival (74.3 %), while those developing de novo DSAs beyond 3 months had the lowest (48.4 %).

In SLK recipients, posttransplant DSAs, especially class II, are significantly associated with increased rejection risk and may contribute to reduced long-term survival. Although preformed DSAs showed less clinical impact, persistent class II DSAs warrant closer monitoring. Larger studies are needed to validate these findings and guide individualized immunological risk assessment.