Impact of HLA-C and Bw epitopes disparity on liver transplantation outcome.
The occurrence of graft rejection episodes after orthotopic liver transplantation (OLT) despite the use of immunosuppressive drugs designed to suppress T lymphocyte functions, indicates the involvement of other types of cells in this process. The activity of natural killer cells and their killer immunoglobulin-like receptors (KIR) is regulated by human leukocyte antigen (HLA) class I determinants; C and Bw epitopes. Because recipient/donor pairs are usually HLA mismatched, recipient natural killer alloreactivity may be the mediating factor in rejection. In this retrospective study, we have analyzed rejection occurrence and outcome in 66 OLT recipients, 42 with and 24 without C or Bw epitope disparity in the rejection direction. Recipients transplanted from donors with no C epitope disparity had significantly fewer rejection episodes in the first year after transplantation compared with recipients transplanted across C epitope disparity (p = 0.0002). Moreover, this effect was more pronounced when the outcome was analyzed in OLT recipients across negative crossmatching for the anti-HLA class I and II antibodies. In contrast, Bw epitope disparity did not affect the outcome. In conclusion, C epitopes disparity between recipients and donors in the rejection direction appears to influence posttransplant liver outcome. This finding may be helpful in the choice of appropriate liver donor and planning immune suppression.
Bishara
Amal
A
Tissue Typing Unit, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. anal@hadassah.org.il
Brautbar
Chaim
C
Zamir
Gideon
G
Eid
Ahmed
A
Safadi
Rifaat
R
D000328:Adult; D000939:Epitopes / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000150:complications / Q000276:immunology*; D015236:HLA-C Antigens / Q000009:adverse effects / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000009:adverse effects / Q000145:classification / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000378:metabolism; D016896:Treatment Outcome
D000939:Epitopes; D015236:HLA-C Antigens; D007518:Isoantibodies; D054340:Receptors, KIR