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

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.