title: Non-HLA antibodies targeting vascular receptors enhance alloimmune response and microvasculopathy after heart transplantation.
abstract: BACKGROUND
  Non-human leukocyte antigen antibodies (Abs) targeting vascular receptors are implicated in the pathogenesis of renal allograft vascular rejection and in progressive vasculopathy in patients with systemic sclerosis.
  
  
  METHODS
  We prospectively tested in 30 heart transplant recipients the impact of Abs directed against endothelin-1 type A (ET(A)R) and angiotensin II type 1 receptors (AT(1)R, cell-enzyme-linked immunosorbent assay) at time of transplantation and during the first posttransplantation year on cellular and Ab-mediated rejection (immunohistochemistry, C3d, and immunoglobulins) and microvasculopathy in endomyocardial biopsy.
  
  
  RESULTS
  Cellular rejection, Ab-mediated rejection, and microvasculopathy was found in 40% and 13%, 57% and 18%, and 37% and 40% of biopsies at 1 month and 1 year posttransplantation, respectively. Maximum levels of AT(1)R and ET(A)R Abs were higher in patients with cellular (16.5±2.6 vs. 9.4±1.3; P=0.021 and 16.5±2.5 vs. 9.9±1.9; P=0.041) and Ab-mediated rejection (19.0±2.6 vs. 10.0±1.3; P=0.004 and 19.4±2.7 vs. 9.0±1.7; P=0.002), as compared with patients who had no rejection. Patients with elevated AT(1)R Abs (53% [16/30]) or ETAR Abs (50% [15/30]; pretransplantation prognostic rejection cutoff >16.5 U/L) presented more often with microvasculopathy (both, 67% vs. 23%; P=0.048) than patients without.
  
  
  CONCLUSIONS
  Elevated levels of AT(1)R and ET(A)R Abs are associated with cellular and Ab-mediated rejection and early onset of microvasculopathy and should be routinely monitored after heart transplantation.
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany. hiemann@dhzb.de
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Hiemann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Meyer
authors.forename: Ernst
authors.initials: E
authors.lastname: Wellnhofer
authors.forename: Constanze
authors.initials: C
authors.lastname: Schoenemann
authors.forename: Harald
authors.initials: H
authors.lastname: Heidecke
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008297:Male; D055806:Microvessels / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000453:epidemiology / Q000276:immunology*
chemical_list: D000906:Antibodies; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A