title: 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.
authors.affiliation: Department of Immunogenetics, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. pavlova.elena@gmail.com
authors.forename: Y A
authors.initials: YA
authors.lastname: Pavlova
authors.forename: I
authors.initials: I
authors.lastname: Malek
authors.forename: E
authors.initials: E
authors.lastname: Honsova
authors.forename: I
authors.initials: I
authors.lastname: Netuka
authors.forename: J
authors.initials: J
authors.lastname: Sochman
authors.forename: A
authors.initials: A
authors.lastname: Lodererova
authors.forename: L
authors.initials: L
authors.lastname: Kolesar
authors.forename: I
authors.initials: I
authors.lastname: Striz
authors.forename: J
authors.initials: J
authors.lastname: Skibova
authors.forename: A
authors.initials: A
authors.lastname: Slavcev
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000097:blood*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C066855:HGF protein, human; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; C099187:MHC class I-related chain A; D017228:Hepatocyte Growth Factor