Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.
Elena G KamburovaBram W WisseIrma JoostenWil A AllebesArnold van der MeerLuuk B HilbrandsMarije C BaasEric SpieringsCornelis E HackFranka E van ReekumArjan D van ZuilenMarianne C VerhaarMichiel L BotsAdriaan C A D DropLoes PlaisierMarc A J SeelenJan Stephan SandersBouke G HepkemaAnnechien J A LambeckLaura B BungenerCaroline RoozendaalMarcel G J TilanusChristina E VoorterLotte WietenElly M van DuijnhovenMariëlle A C J GelensMaarten H L ChristiaansFrans J van IttersumShaikh A NurmohamedNeubury M LardyWendy SwelsenKarlijn A M I van der PantNeelke C van der WeerdIneke J M Ten BergeFrederike J BemelmanAndries J HoitsmaPaul J M van der BoogJohan W de FijterMichiel G H BetjesSebastiaan HeidtDave L RoelenFrans H ClaasHenny G OttenPublished in: Journal of the American Society of Nephrology : JASN (2018)
Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.