Clinical Significance of Post-Transplant HLA Class II Donor-Specific Antibodies in the Development of Rejection and Clinical Outcomes in Paediatric Liver Transplantation: A Retrospective Single-Centre Study

Abstract

To evaluate the clinical relevance of post-transplant anti-HLA class II donor-specific antibodies (DSA) in paediatric liver transplantation (LT) recipients. We performed a retrospective cohort study including 346 paediatric patients who underwent LT between January 2019 and December 2022 at our centre. Based on the HLA class II DSA status, we divided the patients into the class II DSA-positive (n = 74) and class II DSA-negative (n = 272) groups. Demographic data, biopsy-proven rejection, DSA characteristics, clinical outcomes, and post-transplantation complications data were compared between groups. Our study consisted of 346 eligible paediatric LT recipients. Of these patients, 74 (21.4%) patients were positive for class II DSA and 272 (78.6%) were negative for class II DSA. The median and interquartile range between LT and class II DSA assessment was 12 (3–24) months post-transplant. Compared with the class II DSA-negative patients, post-transplant class II DSA was associated with a significantly increased risk of T cell-mediated rejection (p = 0.033) and antibody-mediated rejection (p = 0.045). Postoperatively, the incidence of cytomegalovirus infection (p = 0.003) and fungal infection (p = 0.007) was higher in the class II DSA-positive group than in the class II DSA-negative group. The frequency of adverse events, including biliary complications (p < 0.001) and intestinal flora alteration (p = 0.007), occurred more frequently in the class II DSA-positive group. Multivariable analyses showed that post-transplant class II DSA was an independent risk factor for T cell-mediated rejection (OR 2.027, 95% CI: 1.109–3.706, p = 0.022). Within the class II DSA-positive group, 22 (30.6%) patients developed T cell-mediated rejection post-transplant, 5 (6.9%) for DSA against HLA-DR, 12 (16.2%) for DSA against HLA-DQ, and 5 (6.7%) for DSA against HLA-DR + HLA-DQ. The MFI value for class II DSA was not significantly higher for patients with T cell-mediated rejection than for those without it. In conclusion, we demonstrated that the incidence of AMR among patients who developed class II DSAs after transplantation was higher than that of those who were negative for class II DSAs. Moreover, post-transplant class II DSA was an independent risk factor for post-transplantation TCMR. These results suggest that monitoring of class II DSA was a useful tool for paediatric LT recipients. However, due to the relatively small sample size of our study, further research with a larger sample size is needed for verification.