Evidence that HLA class II disparity is required for the induction of renal allograft enhancement by donor-specific blood transfusions in man.
We studied 46 living-related primary renal allograft recipients between June 1980 and Jan 1988 to determine if enhancement of allograft survival by donor specific transfusions requires a major histocompatibility complex mismatch between the blood/kidney donor and the recipient. Recipients were matched for a single HLA haplotype, but differed at various HLA loci on the unshared haplotype. DST (200 ml) was administered either 3 times at two-week intervals pretransplant (n = 17), or once 3-4 weeks pretransplant, together with oral azathioprine (1 mg/kg/day/28 days) (n = 29). Patients were followed for at least 1 year and all clinical rejection episodes were confirmed histologically. Enhanced graft survival by DST was defined as a rejection-free posttransplant course. Incompatibility for class II determinants on the unshared haplotype of donor had a beneficial effect. A significantly greater proportion of recipients had stable, rejection-free, allograft function if incompatible for the DR locus (80% vs. 44%, P = 0.012), for class II public determinants (100% vs. 58%, P = 0.013), or for at least one of the class II gene products (DR, DQ, class II public) (81% vs. 40%, P = 0.006). Graft loss occurred in 7 of 46 (15%); 6 of the 7 recipients were HLA class II-compatible with their blood/kidney donor. Mismatches for HLA class I private or public determinants and other factors known to affect graft outcome did not influence the results. We conclude that enhanced kidney allograft survival by DST may be predicated by factors within the MHC--specifically class II disparity. These observations also suggest that better HLA matching at the class II locus may account for the apparent "disappearance" of the transfusion effect in cadaver renal transplants in the cyclosporine era.
Lazda
V A
VA
Department of Surgery, University of Illinois, Chicago 60680.
Pollak
R
R
Mozes
M F
MF
Barber
P L
PL
Jonasson
O
O
D001803:Blood Transfusion; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D006648:Histocompatibility / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D014019:Tissue Donors; D014184:Transplantation, Homologous
D006680:HLA Antigens