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Immune monitoring and Biomarkers

Monday September 23, 2024 - 13:40 to 15:10

Room: Üsküdar 3

247.12 Value of HLA class II combined molecular mismatch scoring system for immune risk stratification in kidney transplantation

Kevin Louis, France

Assistant professor
Nephrology
Saint Louis hospital

Abstract

Value of HLA class II combined molecular mismatch scoring system for immune risk stratification in kidney transplantation

Kevin Louis1, Mitchell Ellison2, Gillian Divard1, Zeynep Demir1, Caroline Sayegh1, Qingyong Xu2, Massimo Mangiola2, Alexandre Loupy1, Adriana Zeevi2, Carmen Lefaucheur1.

1Paris Institute for Transplantation and Organ Regeneration, Université Paris Cité, INSERM, U-970, Paris, France; 2University of Pittsburgh Medical Center, Histocompatibility Laboratory, Pittsburgh, PA, United States

Introduction: HLA class II eplet mismatch (epMM) and predicted indirectly recognizable HLA epitopes (PIRCHE-II) algorithms represent promising tools for immune risk assessment post-transplant. Yet, only few studies have explored the value of a combined (i.e. epMM and PIRCHE-II) molecular mismatch score for post-transplant immune risk stratification.
Methods: We included 545 patients who received kidney transplantation between 2011 and 2016 in three centers in Paris. High resolution HLA typing was performed via NGS sequencing to determine HLAMatchmaker epMM and PIRCHE-II scores for DR, DQ and DR+DQ loci. Risk cut-offs for post-transplant DSA were determined based on the epMM and PIRCHE-II scores that corresponded to 95% or greater sensitivity and maximized specificity. Combined (epMM and PIRCHE-II) scores were calculated and assigned to three risk categories (low, intermediate and high) for DR, DQ and DR+DQ loci and Kaplan Meir analyses for DSA and antibody-mediated rejection (ABMR) were performed.
Results: EpMM risk cut-offs predicted the risk of post-transplant DSA and ABMR. When used in combination with PIRCHE-II risk cut-offs, patients could be further stratified into low-, intermediate-, and high-risk categories. Combined scores for DR were significantly associated with risk of developing DR-DSA, patients at low risk exhibited a higher rate of freedom from DR-DSA compared to patients at high risk (P<0.0001). Patients with low combined scores for DQ had a low risk of developing DQ-DSA compared to patients at intermediate and high risk (P=0.0059). Combined low scores for both DR+DQ loci were also significantly associated with freedom from DR and DQ DSA (P=0.02). Finally, combined scores for DR+DQ could stratify patients at low risk of developing ABMR from patients at intermediate and high risk (P=0.027).
Conclusion: Integration of both HLA class II epMM and PIRCHE-II algorithms into a combined molecular mismatch score enables more granular immune risk stratification for post-transplant DSA and ABMR. This risk evaluation strategy may enable individualized immune monitoring and thus personalized immunosuppression in kidney transplantation.

References:

[1] HLA antibodies
[2] HLA mismatch
[3] graft rejection
[4] kidney transplantation
[5] graft survival

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