Frontiers in immunology · 2026
Association of PIRCHE scores and allograft injury in kidney transplant recipients.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Molnar Miklos Z, Holdaway Kendon J, Raghavan Divya, Marineci Silviana, Oygen Suayp, Toth Fruzsina, Fornadi Katalin
Аннотация
BACKGROUND: Early allograft injury during the first year after kidney transplantation is a major determinant of long-term graft survival. Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) quantify donor-derived human leucocyte antigen (HLA) peptides presented to recipient CD4+ T cells via the indirect pathway and may capture alloimmune risk beyond conventional HLA mismatch.
METHODS: In this single-center retrospective cohort study, we evaluated adult kidney transplant recipients transplanted between 2021 and 2024. Five-locus PIRCHE-T2 (T-cell epitope load) and PIRCHE-B (surface-accessible amino acid mismatch) scores were calculated using high-resolution HLA typing with imputation when necessary. The primary endpoint was a composite of post-transplant allograft injury within one year, including donor-specific antibody (DSA) development, histologic or molecular rejection, or elevation of donor-derived cell-free DNA (dd-cfDNA). Secondary endpoints were each component analyzed separately. Predictive performance was assessed using receiver operating characteristic analysis and compared to the only HLA A/B/DR antigen mismatch model, and associations were evaluated using Cox proportional hazards models.
RESULTS: Among 683 recipients, 250 (37%) experienced the primary endpoint. Higher five-locus PIRCHE-T2 and PIRCHE-B scores were significantly associated with the composite outcome [adjusted hazard ratio (HR)(95% confidence interval (CI)] per point increase 1.009(1.004-1.014) and 1.043(1.027-1.060), and adjusted HR low versus high risk 1.653(1.254-2.180) and 2.280(1.664-3.123), respectively). Both scores demonstrated modest discriminatory performance (area under the curve (AUC) 0.575-0.621). Higher PIRCHE scores were also independently associated with increased risk of de novo or recurrent DSA, dd-cfDNA elevation, and showed trends toward increased rejection risk. Sensitivity analyses incorporating six-locus PIRCHE-T2 (including DQA1) yielded consistent results. Compared with HLA A/B/DR antigen-mismatch models, PIRCHE-B scores improved prediction primarily for DSA, whereas PIRCHE-T2 did not add predictive value for outcomes.
CONCLUSIONS: Higher PIRCHE scores are associated with increased risk of early alloimmune injury after kidney transplantation across multiple complementary biomarkers. Although discriminatory performance was modest, PIRCHE provides mechanistically grounded risk stratification and may complement existing immunologic assessment strategies.
METHODS: In this single-center retrospective cohort study, we evaluated adult kidney transplant recipients transplanted between 2021 and 2024. Five-locus PIRCHE-T2 (T-cell epitope load) and PIRCHE-B (surface-accessible amino acid mismatch) scores were calculated using high-resolution HLA typing with imputation when necessary. The primary endpoint was a composite of post-transplant allograft injury within one year, including donor-specific antibody (DSA) development, histologic or molecular rejection, or elevation of donor-derived cell-free DNA (dd-cfDNA). Secondary endpoints were each component analyzed separately. Predictive performance was assessed using receiver operating characteristic analysis and compared to the only HLA A/B/DR antigen mismatch model, and associations were evaluated using Cox proportional hazards models.
RESULTS: Among 683 recipients, 250 (37%) experienced the primary endpoint. Higher five-locus PIRCHE-T2 and PIRCHE-B scores were significantly associated with the composite outcome [adjusted hazard ratio (HR)(95% confidence interval (CI)] per point increase 1.009(1.004-1.014) and 1.043(1.027-1.060), and adjusted HR low versus high risk 1.653(1.254-2.180) and 2.280(1.664-3.123), respectively). Both scores demonstrated modest discriminatory performance (area under the curve (AUC) 0.575-0.621). Higher PIRCHE scores were also independently associated with increased risk of de novo or recurrent DSA, dd-cfDNA elevation, and showed trends toward increased rejection risk. Sensitivity analyses incorporating six-locus PIRCHE-T2 (including DQA1) yielded consistent results. Compared with HLA A/B/DR antigen-mismatch models, PIRCHE-B scores improved prediction primarily for DSA, whereas PIRCHE-T2 did not add predictive value for outcomes.
CONCLUSIONS: Higher PIRCHE scores are associated with increased risk of early alloimmune injury after kidney transplantation across multiple complementary biomarkers. Although discriminatory performance was modest, PIRCHE provides mechanistically grounded risk stratification and may complement existing immunologic assessment strategies.