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DQA1-Derived Indirect T Cell Epitope Load Associates With Immune Injury Markers in Pediatric Liver Transplant Recipients

Year: 2026

Type: article

Abstract: Background. Human leucocyte antigen molecular mismatch (MMM) may contribute to alloimmune risk after transplantation; however, its predictive value in pediatric liver transplantation (LT) remains incompletely defined. We hypothesized that higher MMM quantified by PIRCHE-T2 would be associated with the development of de novo donor-specific antibodies (dnDSA) and graft injury markers, including liver allograft fibrosis and T cell–mediated rejection (TCMR). Methods. We retrospectively studied pediatric isolated LT recipients with available 2-field class II human leucocyte antigen typing for donor and recipient. MMM was calculated using PIRCHE-T2. Endpoints included dnDSA development, TCMR, and liver allograft fibrosis. Results. One hundred and ninety children made up the study cohort. In univariate analysis, younger recipient age and increased DQA1-derived PIRCHE-T2 MMM load were associated with dnDSA development ( P = 0.04 and P < 0.0001, respectively). In multivariable analysis, increased DQA1-derived mismatch remained strongly associated with dnDSA development (odds ratio [OR], 9.49; 95% CI, 5.08-20.2; P < 0.001), while older recipient age remained protective (OR, 0.89; 95% CI, 0.81-0.98; P = 0.017). Increased DQA1-derived mismatch and higher tacrolimus variability were also associated with shorter dnDSA-free survival (hazard ratio [HR], 2.26, P < 0.001 and HR, 1.11, P = 0.001, respectively). Recipients with dnDSA demonstrated shorter fibrosis-free survival (HR, 2.64; 95% CI, 1.13-6.17; P = 0.025), while TCMR was strongly associated with dnDSA positivity ( P < 0.0001). dnDSA demonstrated a sensitivity of 0.70, specificity of 0.90, positive predictive value of 0.68, and negative predictive value of 0.90 for TCMR. Conclusions. Increased DQA1-derived MMM assessed by PIRCHE-T2 was strongly associated with dnDSA development and shorter dnDSA-free survival after pediatric LT. In turn, dnDSA was associated with TCMR and shorter fibrosis-free survival, supporting a link between MMM, humoral alloimmune activation, and clinically relevant graft injury.

Source: Transplantation Direct

DOI: 10.1097/txd.0000000000002017