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Abstract: FR-OR61

Correlation of HLA Matchmaker and PIRCHE Reveals T Cell Epitope Mismatches High Risk for Donor Specific Antibodies (DSA) and Antibody-Mediated Rejection (AMR)

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Crane, Clarkson, University of California San Diego School of Medicine, La Jolla, California, United States
  • Ingulli, Elizabeth G., University of California San Diego School of Medicine, La Jolla, California, United States
  • Morris, Gerald P., University of California San Diego School of Medicine, La Jolla, California, United States
Background

Both HLA Matchmaker and PIRCHE algorithms associate with de novo donor specific antibody (DSA) in kidney transplant recipients (KTR), but each predicts a different mechanism of the alloimmune response. Activation of CD4 T helper cells via indirect allorecognition (PIRCHE) occurs upstream of T-B cooperation resulting in antibody production (HLA Matchmaker). Given this, we aim to describe their correlation and hypothesize PIRCHE can provide insight as to the molecular mismatches highest risk for DSA and subsequent rejection.

Methods

KTR between 2017 to 2022 with high-resolution HLA typing were identified. Eplet mismatches were calculated with HLA Matchmaker and PIRCHE score determined. Spearman correlation was preformed and results plotted with quintile cutoffs.

Results

We identified 420 adult (n= 377) and pediatric (n= 43) KTR. Median age 52 years old, 68% male, 68% deceased donor and median time 20 months from transplant.

DQA1/DQB1 had the strongest association with DSA when assessed with each algorithm. Distribution and correlation of PIRCHE and eplet mismatches for the entire cohort, +DSA, TCMR and AMR are shown in Figure 1, panels A-D. There was moderate correlation between the algorithms but more discordance of high PIRCHE/low eplet mismatch in DSA and AMR.

Conclusion

Our results demonstrate moderate strength correlation of PIRCHE and HLA matchmaker with transplant outcomes. High PIRCHE in setting of lower eplet mismatch in those with DSA and AMR suggests PIRCHE is predicting mismatched T cell epitopes that may be relevant for antibody formation and rejection. This cohort is limited by its retrospective nature and small sample size, but our next phase aims to test this hypothesis by quantifying ex vivo alloreactivity in donor/recipient pairs with high predicted T-cell epitope mismatches.