Date: Monday, June 4, 2018
Session Time: 2:30pm-4:00pm
Presentation Time: 3:18pm-3:30pm
Location: Room 4B
Introduction: HLA matching at the epitope level offers new opportunities to identify compatible donors for transplant candidates. HLAMatchmaker deduces B-cell epitope ('eplets' in HLAMatchmaker) mismatches from allele-level donor-recipient HLA types. We hypothesized that antibody verification informs immunogenicity and antibody-verified mismatches confer greater risk for graft loss than all eplet mismatches.
Methods: Using SRTR, we conducted a retrospective cohort study in unsensitized first kidney transplant recipients (KTR) transplanted between Jan. 1, 2000 to Sept. 2, 2015. KTR with multi-organ transplants, primary graft non-function or without allele-level HLA types were excluded. All and antibody-verified eplets (www.Epregistry.com.br) were ascertained from allele-level donor-recipient HLA types imputed from serologic types by the National Marrow Donor Program algorithm. We fit multivariable Cox proportional hazards models to determine the independent association between class I (HLA-A and -B) and II (-DR) eplet mismatches and death-censored graft loss. All-cause graft loss was a secondary endpoint.
Results: A total of 118,382 KTR were included. Hazard ratios (HR) for death-censored graft loss were higher for antibody-verified compared with all eplet mismatches. HR associated with each additional 1, 5, and 10 HLA eplet mismatches for Class I and II are shown in Table 1. Similar trends were observed for all-cause graft loss.
|Epitope MM||1 MM|
HR (95% CI)
HR (95% CI)
HR (95% CI)
|Class I AbV||1.011 (1.010, 1.013)||1.056 (1.051, 1.067)||1.116 (1.105, 1.138)|
|Class I All||1.005 (1.004, 1.006)||1.025 (1.020, 1.030)||1.051 (1.041, 1.062)|
|Class II AbV||1.020 (1.017, 1.022)||1.104 (1.088, 1.115)||1.219 (1.184, 1.243)|
|Class II All||1.009 (1.007, 1.010)||1.046 (1.035, 1.051)||1.094 (1.072, 1.105)|
Conclusion: A quantitatively greater risk of graft loss with larger numbers of antibody-verified compared with all eplet mismatches, suggests that antibody-verified eplets portend greater immune-risk. Whether a cumulative burden of antibody-verified or immunodominant eplet mismatches determines outcomes is unknown.
CITATION INFORMATION: Sapir-Pichhadze R., Zhang X., Ferradji A., Madbouly A., Fingerson S., Tinckam K., Gebel H., Cardinal H., Foster B. Antibody-Verified Eplet Mismatches as Determinants of Premature Kidney Transplant Loss Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Sapir-Pichhadze R, Zhang X, Ferradji A, Madbouly A, Fingerson S, Tinckam K, Gebel H, Cardinal H, Foster B. Antibody-Verified Eplet Mismatches as Determinants of Premature Kidney Transplant Loss [abstract]. https://atcmeetingabstracts.com/abstract/antibody-verified-eplet-mismatches-as-determinants-of-premature-kidney-transplant-loss/. Accessed August 18, 2019.
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