Donor/Recipient HLA Molecular Mismatch Scores Predict Primary Humoral and Cellular Alloimmunity in Kidney Transplantation

By: Maria Meneghini, Elena Crespo, Matthias Niemann, Alba Torija, Nuria Lloberas, Vincent Pernin, Pere Fontova, Edoardo Melilli, Alexandre Favà, Nuria Montero, Anna Manonelles, Josep Maria Cruzado, Eduard Palou, Jaume Martorell, Josep Maria Grinyó, Oriol Bestard

Published: in Frontiers in Immunology 2021; Front. Immunol. 11:623276 (March 2021). 

Patients: 169

Highlights:

  • This study hypothesizes that donor/recipient HLA mismatches assessed at the molecular level may also influence a higher susceptibility to the development of posttransplant primary T-cell alloimmunity.

  • 169 consecutive kidney transplant recipients without preformed donor-specific antibodies (DSA) and with high resolution donor/recipient HLA typing were evaluated for HLA molecular mismatch scores using different informatic algorithms: Amino acid mismatch, eplet MM, and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II)

  • A strong correlation was observed between the three distinct molecular mismatch scores and they all accurately predicted dnDSA formation, in particular at the DQ locus.

  • HLA molecular incompatibility predicted the advent of dnDST, especially when assessed by PIRCHE-II score.

  • In vitro experiments showed that posttransplant DST may also be activated by the indirect pathway of alloantigen presentation, and predominantly driven by CD4+ alloreactive T cells in a significant proportion of patients.