Impact of donor mismatches at individual HLA-A, -B, -C, -DR, and -DQ loci on the development of HLA-specific antibodies in patients listed for repeat renal transplantation.
We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus-specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus. Two-thirds of patients awaiting repeat transplantation were sensitized (calculated reaction frequency over 15%) and half were highly sensitized (calculated reaction frequency of 85% and greater). Antibody levels peaked after re-listing for repeat transplantation, were independent of graft nephrectomy and were associated with length of time on the waiting list (odds ratio 8.4) and with maintenance on dual immunosuppression (odds ratio 0.2). Sensitization was independently associated with increasing number of donor HLA mismatches (odds ratio 1.4). All mismatched HLA loci contributed to the development of HLA locus-specific antibodies (HLA-A: odds ratio 3.2, HLA-B: odds ratio 3.4, HLA-C: odds ratio 2.5, HLA-DRB1: odds ratio 3.5, HLA-DRB3/4/5: odds ratio 3.9, and HLA-DQ: odds ratio 3.0 (all significant)). Thus, the risk of allosensitization following failure of a first renal transplant increases incrementally with the number of mismatches at all HLA loci assessed. Maintenance of re-listed patients on dual immunosuppression was associated with a reduced risk of sensitization.
Department of Surgery, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Vasilios
V
Kosmoliaptsis
Department of Surgery, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Olivera
O
Gjorgjimajkoska
MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK.
Linda D
LD
Sharples
Department of Renal Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Afzal N
AN
Chaudhry
Department of Surgery, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Nikolaos
N
Chatzizacharias
Histocompatibility and Immunogenetics Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Sarah
S
Peacock
Department of Renal Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Nicholas
N
Torpey
Department of Surgery, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Eleanor M
EM
Bolton
Histocompatibility and Immunogenetics Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Craig J
CJ
Taylor
Department of Surgery, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
J Andrew
JA
Bradley
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D017211:Treatment Failure; D014850:Waiting Lists; D055815:Young Adult
D015415:Biomarkers; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies