Exploring predicted indirectly recognizable HLA epitopes (PIRCHE-II) in liver transplant recipients on calcineurin inhibitor-free maintenance immunosuppression. A retrospective single center study

Transpl Immunol. 2020 Apr:59:101272. doi: 10.1016/j.trim.2020.101272. Epub 2020 Feb 12.

Abstract

The PIRCHE (Predicted Indirectly ReCognizable HLA Epitopes) score is an HLA epitope matching algorithm. PIRCHE algorithm estimates the level of presence of T-cell epitopes in mismatched HLA. The PIRCHE-II numbers associate with de novo donor-specific antibody (dnDSA) formation following liver transplantation and kidney allograft survival following renal transplantation. The aim of our study was to assess the PIRCHE-II score in calcineurin inhibitor (CNI)-free maintenance immunosuppression recipients. This was a retrospective study of forty-one liver transplant recipients on CNI-free immunosuppression and with available liver allograft biopsies. Donors and recipients were HLA typed. The HLA-derived mismatched peptide epitopes that could be presented by the recipient's HLA-DRB1 molecules were calculated using PIRCHE-II algorithm. The associations between PIRCHE-II scores and graft immune-mediated events were assessed using receiver operating characteristics curves and subsequent univariate and multivariate analyses. CNI-free patients with cellular rejection, humoral rejection, or severe portal inflammation had higher mean PIRCHE-II scores compared to patients with normal liver allografts. PIRCHE-II score and donor age were independent risk factors for liver graft survival in CNI-free patients (HR: 8.0, 95% CI: 1.3-49, p = .02; and HR: 0.88, 95% CI: 0.00-0.96, p = .007, respectively). PIRCHE-II scores could be predictive of liver allograft survival in CNI-free patients following liver transplantation. Larger studies are needed to confirm these results.

Keywords: Donor-specific alloantibodies; HLA epitope mismatch; Immunosuppression minimization.

MeSH terms

  • Adult
  • Calcineurin / therapeutic use
  • Epitopes / immunology
  • Female
  • Graft Rejection / drug therapy
  • Graft Rejection / immunology*
  • Graft Survival
  • HLA Antigens / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Transplant Recipients

Substances

  • Epitopes
  • HLA Antigens
  • Immunosuppressive Agents
  • Calcineurin