Characteristics and predictive value for graft fibrosis of the complement-binding capacity of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation

Background: Donor-specific HLA antibodies (DSAs) have detrimental effects on short- and long-term outcomes after organ transplantation. Despite evidence that the complement-binding capacity of DSAs has predictive power in kidney transplantation, its clinical impact during long-term follow-up after LT remains unclear. In this study, we assessed the complement-binding capacities of DSAs and their association with histological findings. Methods: In total, 72 patients who underwent pediatric LT at our institution between July 1991 and October 2013 were retrospectively reviewed. A subgroup analysis of histological findings was performed for 37 subjects who underwent liver graft biopsy. Patients were divided into two groups based on the degree of graft fibrosis, and clinical characteristics were assessed. Results: All anti-class I DSAs were C1q-negative. Anti-DR and anti-DQ DSAs were identified in 34% and 41% of patients, respectively; however, only three of 25 patients with anti-DR DSAs exhibited a positive C1q-binding assay, whereas, 25 of 29 anti-DQ DSAs showed C1q-binding capacity. MFI values for DSA were significantly higher for patients with C1q-binding capacity than for those without (P <.0001). Complement-binding anti-DR DSA was relatively rare in both groups. Regarding anti-DQ DSA, there were no differences between fibrosis and non-fibrosis groups, irrespective of complement-binding capacity. Conclusions: The association between anti-DR DSA and liver fibrosis, which was supported in this cohort, was not strengthened but rather impaired when accounting for complement-binding capacity due to low positive detection. Further studies of the association between complement-binding anti-DQ DSA and histological findings in LT are needed.