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. 2021 Dec;36(12):3971-3979.
doi: 10.1007/s00467-021-05078-9. Epub 2021 Jun 7.

Eplet mismatches associated with de novo donor-specific HLA antibody in pediatric kidney transplant recipients

Olga Charnaya  1 , June Jones  2 , Mary Carmelle Philogene  3 , Po-Yu Chiang  4 , Dorry L Segev  4   5 , Allan B Massie  4 , Jacqueline Garonzik-Wang  4
Affiliations

Eplet mismatches associated with de novo donor-specific HLA antibody in pediatric kidney transplant recipients

Olga Charnaya et al. Pediatr Nephrol. 2021 Dec.

Abstract

Background: Optimizing amino acid (eplet) histocompatibility at first transplant decreases the risk of de novo donor-specific antibody (dnDSA) development and may improve long-term graft survival in pediatric kidney transplant recipients (KTR). We performed a retrospective analysis of pediatric KTR and their respective donors to identify eplets most commonly associated with dnDSA formation.

Methods: Eplet mismatch analysis was performed in a cohort of 125 pediatric KTR-donor pairs (2006-2018). We determined the prevalence of each eplet mismatch and quantified the percentage of exposed patients who developed dnDSA for each mismatched eplet.

Results: Recipient median age was 14 (IQR 8-17) years with a racial distribution of 42% Black, 48% Caucasian, and 5.6% Middle-Eastern. Median eplet load varied significantly by recipient race, Black 82 (IQR 58-98), White 60 (IQR 44-81) and Other 66 (IQR 61-76), p = 0.002. Forty-four percent of patients developed dnDSA after median 37.1 months. Compared to dnDSA- patients, dnDSA+ patients had higher median eplet load, 64 (IQR 46-83) vs. 77 (IQR 56-98), p = 0.012. The most common target of dnDSA were eplets expressed in HLA-A*11 and A2 in Class I, and HLA-DQ6 and DQA5 in Class II. The most commonly mismatched eplets were not the most likely to result in dnDSA formation.

Conclusions: In a racially diverse population, only a subset of eplets was linked to antibody formation. Eplet load alone is not a sufficient surrogate for eplet immunogenicity. These findings illustrate the need to optimize precision in donor selection and allocation to improve long-term graft outcomes. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: De novo DSA; Eplet mismatch; Kidney transplant; Pediatric.

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Conflict of interest statement

DISCLOSURE

The authors of this manuscript have no conflicts of interest to disclose as described by the Journal of Pediatric Nephrology.

DECLARATIONS

Conflicts of interest/Competing interests: The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Thirty Most Common Eplet Mismatches
Figure 2.
Figure 2.
Thirty Most Common dnDSA Targets
Figure 3.
Figure 3.
The Prevalence of Eplet Mismatch Exposure and dnDSA Development among Exposed Recipients
See this image and copyright information in PMC

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