title: Impaired circulating dendritic cell reconstitution identifies rejecting recipients after clinical heart transplantation independent of rejection therapy.
abstract: OBJECTIVE
  Dendritic cell (DC) mediated allo-antigen presentation to host antigen specific T-lymphocytes initiates acute allograft rejection. We investigated peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to histological diagnosis of acute cellular rejection (AR) and administration of rejection therapy after clinical heart transplantation (post-HTx).
  
  
  METHODS
  Venous blood from 20 HTx recipients under standard immunosuppression was collected during serial endomyocardial biopsy (EMB) prior to administration of rejection therapy in a 9-month follow-up post-HTx. Echocardiographic assessment of allograft function during EMB was performed to distinguish clinical necessity for rejection therapy within histologically rejecting patients (R). Myeloid (mDC) and plasmacytoid (pDC) subsets identified by flow-cytometry were analysed for different ISHLT rejection grades. Circulating PBDC incidence and mDC/pDC ratio were compared sequentially between non-rejecting (NR) recipients and R patients treated (3A(+)) or not-treated (3A(-)) with rejection therapy during follow-up.
  
  
  RESULTS
  Eleven samples from biopsy-proven AR episodes (AR(+): ISHLT>or=3) were compared to 89 samples from non-rejection episodes (AR(-): ISHLT grade 0, n=52; grade 1, n=29; grade 2, n=8). We observed an inverse correlation of mDCs (P<0.05) but not pDCs with increasing rejection grade. PBDC incidence and mDC/pDC ratio were low in blood samples obtained during AR (P<0.05 and P<0.01, respectively). Both PBDCs and mDC/pDC ratio decreased during each AR episode (P<0.05). Comparison of 3A(+) and 3A(-) rejectors with NR patients after 12 weeks post-HTx revealed lower PBDC incidence (P<0.01) and mDC/pDC ratio (P<0.05) for R patients, independent of rejection therapy.
  
  
  CONCLUSIONS
  Defective DC subset reconstitution by dendritic cell profiling identifies patients at risk for AR after 3 months post-HTx. This finding may contribute to further optimization of immunosuppressive treatment strategies after clinical heart transplantation.
authors.affiliation: Department of Cardiothoracic Surgery, University Medical Center Rotterdam, Erasmus MC, Rotterdam, The Netherlands. p.athanassopoulos@erasmusmc.nl <p.athanassopoulos@erasmusmc.nl>
authors.forename: Petros
authors.initials: P
authors.lastname: Athanassopoulos
authors.forename: Leonard M B
authors.initials: LM
authors.lastname: Vaessen
authors.forename: Aggie H M M
authors.initials: AH
authors.lastname: Balk
authors.forename: Johanna J M
authors.initials: JJ
authors.lastname: Takkenberg
authors.forename: Alex P W M
authors.initials: AP
authors.lastname: Maat
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Ad J J C
authors.initials: AJ
authors.lastname: Bogers
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000276:immunology / Q000601:surgery*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D007166:Immunosuppressive Agents