Assessment of Donor-Specific Human Leukocyte Antigen Antibodies Following Pediatric Liver Transplantation: Predictors, Protectors, and Clinical Relevance.

BACKGROUND

Following pediatric liver transplantation (pLT), the significance and management of donor-specific antibodies (DSA) against human leukocyte antigen (HLA) remain undefined. The aim of this single-center study was to investigate the occurrence of DSA, their clinical impact on predictors for and protectors against DSA.

PATIENTS AND

METHODS

We compared anti-HLA DSA (cutoff for mean fluorescence intensity (MFI) ≥ 1000), clinical and laboratory results and outcome in a routine (RG, n = 142, standard DSA testing) and a hepatopathy group (HG, n = 19, DSA testing following indeterminate hepatopathy) in 161 pLT patients, treated 2000-2021, retrospectively.

RESULTS

40% of RG and 32% of HG patients were DSA+ (39% of all patients, of which 13% with antibody-mediated rejection [AMR]). Most frequent DSA subtypes were HLA-DQ3, -DQ1, -DQ2 in RG and HLA-DQ2, -DR15 in HG. MFI was higher for anti-HLA II DSA (15 257 DSA+ vs. 5500 DSA-, p = 0.003), especially with AMR (21 000 DSA+ with AMR vs. 14 584 DSA+ without AMR, p = 0.042). Predictors for DSA included age at pLT, re-pLT, and cystic fibrosis. Living donation and cold ischemia time <8 h appeared to offer protection. Graft survival was poorer with DSA (RG 78% DSA+ vs. 97% DSA-, p = 0.018, HG 67% DSA+ vs. 100% DSA-, p = 0.0007). Patient survival was 97% for the entire cohort.

CONCLUSIONS

DSA were detectable in 39% and associated with AMR in 13% of children post-pLT in addition to worse graft survival in all patients. Patient survival of 97% was not influenced. Potential DSA and predictors and protectors were identified. Therefore, DSA diagnostics are recommended after pLT.