Antiendothelial antibodies after heart transplantation: the accelerating factor in transplant-associated coronary artery disease?
Although the precise cause of transplant-associated coronary artery disease is unknown, immune mechanisms have been implicated. Using the techniques of SDS-PAGe and Western immunoblotting, we have previously shown that a strong positive correlation exists between the development of coronary artery disease and the presence of antiendothelial antibodies reactive with a doublet of polypeptides of approximately 60 and 62 kDa. We have now extended this study to investigate the temporal pattern of antiendothelial antibody formation after transplantation and its association with cellular rejection episodes. The original study used patients in whom coronary artery disease had developed early after transplantation, that is at 1 or 2 years. Here we investigate whether antiendothelial antibodies are also made in patients in whom the disease does not develop until 5 to 10 years after heart transplantation and whether the antibodies are found in patients with severe nontransplant atherosclerosis. We confirm the 60 to 62 kDa antigens are membrane bound, and recalculation of their molecular mass makes the doublet 56 and 57.5 kDa. The results show that antibodies specific for the doublet of endothelial antigens are rarely produced by patients other than those in whom rapidly progressing coronary artery disease develops early after transplantation. The antibodies are unrelated to cellular rejection episodes. We believe their production may be an accelerating factor for the rapid development of transplant-associated coronary artery disease.
Crisp
S J
SJ
Heart Science Centre, National Heart and Lung Institute, Harefield Hospital, Middlesex, United Kingdom.
Dunn
M J
MJ
Rose
M L
ML
Barbir
M
M
Yacoub
M H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000032:analysis; D002478:Cells, Cultured; D018834:Chaperonin 60; D003324:Coronary Artery Disease / Q000276:immunology; D003327:Coronary Disease / Q000209:etiology* / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007518:Isoantibodies / Q000032:analysis / Q000276:immunology*; D007519:Isoantigens / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged
D000954:Antigens, Surface; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D007519:Isoantigens; D008565:Membrane Proteins