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Predicted Indirectly Recognizable T-cell Epitope (PIRCHE) Load Correlates With Rejection Events After Simultaneous
Sandesh Parajuli1, Matthias Niemann2, Bethany L Dale2
1Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI.
Transplantation Direct
|February 12, 2025
Summary
Predicted indirectly recognizable T-cell epitope (PIRCHE) scores, specifically PIRCHE-II, are crucial for assessing HLA class II mismatches in simultaneous pancreas-kidney (SPK) transplants. This molecular matching improves rejection risk assessment for SPK recipients.
Area of Science:
- Transplantation immunology
- Molecular diagnostics
- Organ transplantation
Background:
- Current diagnostic methods for pancreas allograft rejection lack specificity.
- Pancreas allograft biopsies are often not feasible due to resistance or inability to perform them.
- There is a need for noninvasive tools to assess rejection risk in simultaneous pancreas-kidney (SPK) transplantation.
Purpose of the Study:
- To investigate the clinical impact of molecular human leukocyte antigen (HLA) matching in a large single-center SPK transplant program.
- To evaluate the utility of various histocompatibility metrics, including eplet and PIRCHE, in predicting rejection events.
- To determine the association between HLA matching and clinical outcomes in SPK recipients.
Main Methods:
- Analysis of 238 SPK recipients transplanted between 2012 and 2021.
- Calculation of HLA mismatches, eplet, Snow, and predicted indirectly recognizable T-cell epitope (PIRCHE) loads using 2-field HLA typing.
- Application of univariable and multivariable Cox proportional hazard and Kaplan-Meier analyses for rejection events and a composite endpoint.
Main Results:
- PIRCHE-II, derived from donor HLA class II, was the only histocompatibility metric significantly correlated with clinical events and rejection post-SPK, particularly pancreas rejections.
- Longer dialysis duration and the type of induction agent used were identified as factors with significant negative impacts on the composite endpoint.
- Kaplan-Meier analyses demonstrated a correlation between PIRCHE class II groups and clinical outcomes.
Conclusions:
- The findings support the clinical utility of incorporating PIRCHE scores for interpreting class II HLA mismatches in SPK transplantation.
- PIRCHE-II offers a valuable noninvasive tool for risk stratification in SPK recipients.
- Optimizing HLA matching through advanced molecular methods like PIRCHE can improve outcomes in SPK transplantation.
