Antibody-Verified Eplet Mismatches as Determinants of Premature Kidney Transplant Loss

R. Sapir-Pichhadze,¹ X. Zhang,¹ A. Ferradji,¹ A. Madbouly,² S. Fingerson,² K. Tinckam,⁵ H. Gebel,³ H. Cardinal,⁴ B. Foster.¹

¹McGill University, Montreal, Canada
²National Marrow Donor Program, Minneapolis
³Emory University Hospital, Atlanta
⁴CHUM, Montreal, Canada
⁵University Health Network, Toronto, Canada.

Meeting: 2018 American Transplant Congress

Abstract number: 208

Keywords: Antibodies, Epitopes, Graft survival, Immunogenicity

Session Information

Session Name: Concurrent Session: Kidney Chronic Antibody Mediated Rejection

Session Type: Concurrent Session

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)	5 MM HR (95% CI)	10 MM HR (95% CI)
	1 MM HR (95% CI)	5 MM HR (95% CI)	10 MM 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 September 21, 2023.

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