General Pathology Resident University of Saskatchewan Saskatoon, SK, Canada
Aim: Despite advances in histocompatibility matching, kidney allograft rejection remains a major clinical challenge. Traditional HLA allele mismatch fails to fully capture the immunologic landscape that underlies rejection risk. This study investigates whether three advanced HLA mismatch algorithms (PIRCHE-II, Eplet Registry (Epregistrry), and SNOW) can differentiate between T cell–mediated rejection (TCMR) and antibody-mediated rejection (AMR). We hypothesize that PIRCHE-II, which models indirect T cell recognition of donor-derived peptides, correlates with TCMR, while epitope-based scores better predict AMR.
Methods: We conducted a retrospective analysis of 594 kidney transplant recipients transplanted between 1981 and 2021 in Saskatchewan. HLA mismatch scores were computed using PIRCHE-II, EpRegistry, and SNOW algorithms. Rejection episodes were categorized by Banff classification (biopsies from 2002 to 2024) as AMR (with antibody-mediated component) or TCMR (with T cell–mediated component). Statistical analyses included Mann–Whitney U and t-tests for group comparisons, and correlation analyses with individual Banff lesion scores (e.g., g, ptc, i, t, v, cg, ct). All data points were verified to ensure adequate sample representation.
Results: Out of 594 patients, 152 (25.6%) experienced biopsy-confirmed rejection. EpRegistry Class II scores were significantly elevated in AMR cases (P < 0.05) and positively correlated with Banff glomerulitis (g) and transplant glomerulopathy (cg) scores. SNOW Class II scores (DR, DQ, and DP loci) also demonstrated strong associations with glomerulitis (g), peritubular capillaritis (ptc), and tubular atrophy (ct) (all P < 0.05) (Fig1). Conversely, PIRCHE-II scores were significantly higher in TCMR cases (P < 0.05), correlating with interstitial inflammation (i), tubulitis (t), and intimal arteritis (v) (P < 0.05) (Fig2). Each algorithm revealed distinct immunopathologic patterns aligned with its biological basis.
Conclusion: PIRCHE-II, SNOW, and EpRegistry offer complementary insight into the mechanisms of kidney allograft rejection. PIRCHE-II aligns with cellular alloimmunity, while epitope mismatch scores better reflect humoral responses. Their associations with specific Banff lesions support their utility in risk stratification and post-transplant monitoring. Incorporating these tools may enable personalized immunosuppression and improve long-term graft outcomes.
