Zakieh Zare, Matthias Niemann, Kasra Shirini, Ian Booth, Bethany Dale, Richard Ugarte, Silke V Niederhaus, Cinthia B Drachenberg, Abdolreza Haririan
Our study suggests that higher B-cell epitope mismatch loads are paradoxically associated with improved pancreas transplant outcomes, while PIRCHE-T2 scores demonstrated limited predictive value.
BACKGROUND: Donor/recipient HLA molecular mismatches are predictive of kidney transplant outcomes. Their role in pancreas transplantation has not been well studied.
METHODS: We conducted a retrospective cohort study in 281 pancreas (± kidney) transplant recipients during 2000-2018, followed for average 53.8 months. T-cell epitope matching was performed by the PIRCHE-II algorithm (T2) and B-cell epitope mismatch using Snow (B2) and HLA Matchmaker algorithms. Primary outcome was pancreas acute rejection, secondary outcomes included pancreas graft failure and composite of both, and kidney graft failure.
RESULTS: PIRCHE-T2 score (59.3±22.3) was not associated with study outcomes (HR 0.99, 95%CI 0.98-1.00, p = 0.31 for pancreas rejection). However, increasing PIRCHE-B score (15.1±6.3) was predictive of lower risk of acute rejection (aHR 0.94; 95%CI 0.9-0.99, p = 0.024) and graft failure (aHR 0.96; 95%CI 0.93-0.99; p = 0.021), driven by PIRCHE-B-Class II score (aHR 0.91; 95%CI 0.85-0.98, p = 0.01; aHR 0.92; 95%CI 0.88-0.97; p = 0.001, respectively). Total eplet mismatch (19.58±7.40) was highly correlated with PIRCHE-B score (ρ = 0.82, p < 0.0001), showing similar associations. However, the molecular scores were not associated with kidney graft failure (p > 0.57 for all).
CONCLUSION: Our study suggests that higher B-cell epitope mismatch loads are paradoxically associated with improved pancreas transplant outcomes, while PIRCHE-T2 scores demonstrated limited predictive value.