Clinical relevance of donor‑specific human leukocyte antigen antibodies after pediatric liver transplantation

Abstract

Donor-specific human leukocyte antigen (HLA) antibodies (DSAs) have a significant role in graft survival after pediatric liver transplantation. To understand the significance of DSAs, a retrospective cohort study of 48 pediatric liver transplant recipients with posttransplant serum samples that were analyzed for DSAs was performed. According to their test results, the recipients were divided into a DSA-positive group and a DSA-negative group. Postoperative liver transplantation biopsies were performed in patients with abnormal liver function. The liver condition and prognosis of the recipients were recorded, and their association was analyzed. A total of 48 recipients were followed up for 2.7±0.8 years. DSA positivity was detected in 10 cases (20.8%). One case was positive for HLA class I and HLA class II antibodies, whereas 9 cases were positive for HLA class II antibodies, and the gene loci were HLA-DR and/or DQ. Antibody-mediated rejection (AMR) occurred in four of 10 patients in the DSA-positive group. Liver function was abnormal in 3 of 38 cases in the DSA-negative group. Multivariate analysis revealed that DSA positivity was an independent risk factor for liver insufficiency and long-term survival of recipients. In addition, Kaplan-Meier survival analysis demonstrated that there were significant differences in the survival of graft recipients between the DSA-positive group and the DSA-negative group (P<0.05). The positivity of DSAs after pediatric liver transplantation was closely related to the occurrence of AMR. These results suggested that DSAs should be routinely monitored post-operatively, and that DSA-positive recipients should be screened as soon as possible and given appropriate treatment.

Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference

“…Therefore, pre‐transplant DSA assessment can be utilized as an immunologic risk stratification measure, to guide post‐transplant transfusion and immunosuppression management, 37–39 rather than an exclusion criterion of an otherwise acceptable donor for LDLT. HLA antibody‐based risk stratification in LDLT recipients with high immunologic risk such as re‐transplant, multiparous women, and pediatric candidates may optimize clinical outcomes 40–42 …”

“…high immunologic risk such as re-transplant, multiparous women, and pediatric candidates may optimize clinical outcomes. [40][41][42] In addition, the deleterious effects of DSA have been reported to be less pronounced in LDLT compared to DDLT, 43 perhaps indicating that LDLT could be an effective strategy to mitigate potential deleterious immunological effects in candidates with a high immunological risk profile.…”

Immunology demystified: A guide for transplant hepatologists

“…A humoral arm of immune system is also able to react on donor HLA molecules by production of DSA. While this possibility was not considered a major issue in the past, the clinical significance of DSA is being increasingly recognised[ 37 , 38 ]. DSA can be either preformed, existing in the patient's circulation before transplantation, or formed de novo, produced after transplantation.…”

Donor-Specific Antibodies and Their Impact on Antibody-Mediated Rejection Post-Liver Transplantation: A Comprehensive Review

“…This suggests that the occurrence of HLA Class II DSA post-LT may indicate a higher risk of graft damage [10]. Next, Liu et al (2021) assessed the impact of DSAs on graft survival following pediatric liver transplantation. Forty-eight recipients were analyzed based on posttransplant serum samples for DSAs.…”

“…One case was positive for HLA class I and HLA class II antibodies, whereas 9 cases were positive for HLA class II antibodies, and the gene loci were HLA-DR and/or DQ. Four of the DSA-positive patients experienced antibody-mediated rejection (AMR) [11]. Noteworthily, the specific HLA antigens involved in AMR can vary between individuals, depending on the genetic differences between the donor and recipient [8,9].…”