title: Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor-Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching.
abstract: We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). 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 effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02-2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02-1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitization than conventional HLA matching.
authors.affiliation: Department of Surgery, University of Cambridge, Cambridge, UK.
authors.forename: V
authors.initials: V
authors.lastname: Kosmoliaptsis
authors.affiliation: Department of Surgery, University of Cambridge, Cambridge, UK.
authors.forename: D H
authors.initials: DH
authors.lastname: Mallon
authors.affiliation: Statistical Laboratory, Centre for Mathematical Sciences, University of Cambridge, Cambridge, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of Cambridge, Cambridge, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Bolton
authors.affiliation: Department of Surgery, University of Cambridge, Cambridge, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Bradley
authors.affiliation: Tissue Typing Laboratory, Cambridge University Hospitals, Cambridge, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Taylor
mesh_terms: D000328:Adult; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies
keywords: alloantibody; alloantigen; histocompatibility; kidney transplantation/nephrology; major histocompatibility complex (MHC); organ allocation; retransplantation; translational research/science