title: Low mannose-binding lectin and increased complement activation correlate to allograft vasculopathy, ischaemia, and rejection after human heart transplantation.
abstract: OBJECTIVE
  Transplant-associated coronary artery disease (TxCAD) is a major cause of post-transplant graft failure. The aim of this study was to investigate a possible role of mannose-binding lectin (MBL) deficiency and complement activation in TxCAD.
  
  
  RESULTS
  In a prospective study of heart transplant recipients (n=38) with a follow-up of 5.3+/-1.3 years (range: 0.9-6.6), angiographically verified TxCAD (n=6) was correlated to plasma MBL, complement activation, and endothelial activation (soluble E-selectin). MBL deficiency (<100 ng/mL) was detected in 3/6 patients with TxCAD and in 3/32 with non-TxCAD (Kaplan-Meier, P=0.020). Furthermore, one or more acute rejection episodes were observed in 6/6 of the MBL-deficient patients and in 15/32 of the MBL-sufficient patients (chi(2); P=0.016). Complement activation (C4bc) correlated with soluble E-selectin (r=0.36; P=0.027), both being significantly higher in patients with ischaemia detected in the first biopsy (C4bc: 13.4+/-6.1 AU/mL; E-selectin: 96+/-13 ng/mL) than in those without ischaemia (C4bc: 6.3+/-0.5; E-selectin: 51+/-6; P=0.037 and 0.002). Finally, terminal complement complex correlated closely with mortality (P=0.002).
  
  
  CONCLUSIONS
  Low MBL was related to the development of TxCAD and acute rejection and increased complement activation correlated to histopathologic ischaemia and mortality after heart transplantation.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
authors.forename: Arnt E
authors.initials: AE
authors.lastname: Fiane
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Svein
authors.initials: S
authors.lastname: Simonsen
authors.forename: Helge
authors.initials: H
authors.lastname: Scott
authors.forename: Knut
authors.initials: K
authors.lastname: Endresen
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Odd R
authors.initials: OR
authors.lastname: Geiran
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haraldsen
authors.forename: Lars
authors.initials: L
authors.lastname: Heggelund
authors.forename: Arne K
authors.initials: AK
authors.lastname: Andreassen
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Wergeland
authors.forename: Stig
authors.initials: S
authors.lastname: Frøland
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation; D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology; D019040:E-Selectin / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood* / Q000209:etiology; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D037601:Mannose-Binding Lectin