Hepatocyte growth factor and antibodies to HLA and MICA antigens in heart transplant recipients

Tissue Antigens. 2010 Nov;76(5):380-6. doi: 10.1111/j.1399-0039.2010.01523.x. Epub 2010 Aug 19.

Abstract

Recent unconfirmed literature data suggest that elevated concentrations of the multifunctional cytokine hepatocyte growth factor (HGF) might be a marker of increased incidence of acute rejection after organ transplantation. The aim of this study was to test the hypothesis that HGF levels may correlate with the rejection and/or with the production of HLA and MHC Class I chain-related antigens A (MICA) specific antibodies. Sixty-three heart transplant recipients were included into the study. Hundred and eighty-five endomyocardial biopsies (EMB) obtained up to 6 months after transplantation were retrospectively analyzed for signs of cellular (CR) and antibody-mediated rejection (AMR). Pre- and post-transplant sera were tested for HGF concentrations and antibodies to HLA class I, class II and MICA antigens by xMap technology (Luminex). Pre-transplant HGF did not correlate with the incidence of CR or AMR. However, higher HGF concentrations correlated significantly with HLA antibody production before and after transplantation (P = 0.006 and P < 0.0001 respectively). Patients with both HLA class I and class II antibodies before transplantation had significantly lower AMR-free survival. Furthermore, recipients with pre-transplant donor-specific antibodies (DSA) had significantly lower AMR-free survival (50%) than recipients without pre-transplant HLA antibodies (90%) and patients with antibodies not specific to donor antigens (92%) (P = 0.005). Post-transplant MICA antibodies tended to be more frequent in patients with AMR (P = 0.063). In conclusion, elevated HGF concentrations in our study were not associated with the incidence of CR and/or AMR but with the presence of HLA-specific antibodies. Testing for DSA before heart transplantation by Luminex may be helpful for the identification of patients with increased risk of AMR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Biomarkers / blood
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology*
  • Graft Rejection / immunology*
  • HLA Antigens / immunology*
  • Heart Transplantation / adverse effects*
  • Heart Transplantation / immunology*
  • Heart Transplantation / pathology
  • Hepatocyte Growth Factor / blood*
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Isoantibodies / blood*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies

Substances

  • Biomarkers
  • HGF protein, human
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Isoantibodies
  • MHC class I-related chain A
  • Hepatocyte Growth Factor