Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance

Transpl Int. 2016 Jan;29(1):63-72. doi: 10.1111/tri.12684. Epub 2015 Sep 22.

Abstract

Solid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panel-reactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.

Keywords: antibody-mediated rejection; heart transplantation; human leukocyte antigens antibodies; prognosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antibody Specificity
  • Chi-Square Distribution
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / immunology*
  • Graft Survival / immunology
  • HLA Antigens / blood*
  • HLA Antigens / immunology
  • Heart Transplantation / adverse effects*
  • Heart Transplantation / methods
  • Heart Transplantation / mortality
  • Histocompatibility Testing
  • Humans
  • Immune Tolerance / physiology
  • Immunization / methods
  • Immunosuppression Therapy / methods*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Preoperative Care / methods
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies
  • Risk Assessment
  • Survival Rate
  • Transplantation Immunology / physiology*
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Treatment Outcome

Substances

  • HLA Antigens