Low mannose-binding lectin and increased complement activation correlate to allograft vasculopathy, ischaemia, and rejection after human heart transplantation.
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.
Fiane
Arnt E
AE
Department of Thoracic and Cardiovascular Surgery, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
Ueland
Thor
T
Simonsen
Svein
S
Scott
Helge
H
Endresen
Knut
K
Gullestad
Lars
L
Geiran
Odd R
OR
Haraldsen
Guttorm
G
Heggelund
Lars
L
Andreassen
Arne K
AK
Wergeland
Ragnhild
R
Frøland
Stig
S
Aukrust
Pål
P
Mollnes
Tom E
TE
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
D015415:Biomarkers; D019040:E-Selectin; D037601:Mannose-Binding Lectin