The role of anti-HLA antibodies in heart transplantation.
The major threat to long-term survival of heart allograft recipients is the development of graft atherosclerosis, which seems to be a manifestation of chronic rejection. To assess the role of anti-HLA antibodies in heart allograft rejection we studied 107 patients and compared the survival of recipients who formed anti-HLA antibodies with the survival of recipients who developed no antibodies. At 4 years the actuarial survival was 90% in the nonproducer group and 38% in antibody-producers (P = 0.038). We further explored the possibility that HLA antigens from the injured graft are released into the circulation and can be found in the serum either free or complexed with anti-HLA antibodies. This hypothesis was confirmed by the finding that the frequency of sera containing soluble HLA antigens from the graft or immune complexes of HLA alloantigens with anti-HLA antibodies was significantly higher in patients who rejected compared with patients with successful heart allografts (P less than 0.05). Following depletion of soluble HLA antigens, anti-HLA antibodies became detectable in 53% and 74% sera obtained during the first and second year posttransplantation, respectively, from patients undergoing chronic rejection. Long-term survivors showed a significantly lower (P less than 0.001) frequency of anti-HLA antibodies in sera depleted of HLA antigens. Lastly, studies of anti-anti-HLA-A2 and A3 antibodies in recipient sera suggest that quiescence is maintained by antiidiotypic antibodies.
Suciu-Foca
N
N
Department of Pathology, College of Physicians & Surgeons of Columbia University, New York, New York 10032.
Reed
E
E
Marboe
C
C
Harris
P
P
Yu
P X
PX
Sun
Y K
YK
Ho
E
E
Rose
E
E
Reemtsma
K
K
King
D W
DW
D000936:Antigen-Antibody Complex / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D012189:Retrospective Studies
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies