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

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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.

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Data availability

Data is available for review upon request to the corresponding author.

Code availability

Not applicable

Abbreviations

dnDSA:

de novo donor specific antibody

MFI:

mean fluorescence intensity

HLA:

human leukocyte antigen

KTR:

kidney transplant recipient

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Acknowledgements

This work was supported by grant number 131918 (Charnaya) from the National Kidney Foundation of Maryland and K24AI144954 (Segev) from the National Institute of Allergy and Infectious Diseases (NIAID). The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the National Kidney Foundation.

Funding

This work was supported by grant number 131918 from the National Kidney Foundation of Maryland.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Johns Hopkins University School of Medicine, 200 N Wolfe St, Baltimore, MD, 21287, USA

    Olga Charnaya

  2. Department of Immunogenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    June Jones

  3. Histocompatibility Laboratory, American Red Cross Penn-Jersey, Philadelphia, PA, USA

    Mary Carmelle Philogene

  4. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Po-Yu Chiang, Dorry L. Segev, Allan B. Massie & Jacqueline Garonzik-Wang

  5. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA

    Dorry L. Segev

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  1. Olga Charnaya
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  2. June Jones
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  4. Po-Yu Chiang
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  5. Dorry L. Segev
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Contributions

OC and MP designed the study, participated in data analysis and manuscript preparation. JJ performed the Immunogenetics laboratory work, PYC participated in data analysis and manuscript preparation. JGW, DS, AM provided mentorship, scientific oversight and participated in manuscript review.

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Correspondence to Olga Charnaya.

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Charnaya, O., Jones, J., Philogene, M.C. et al. Eplet mismatches associated with de novo donor-specific HLA antibody in pediatric kidney transplant recipients. Pediatr Nephrol 36, 3971–3979 (2021). https://doi.org/10.1007/s00467-021-05078-9

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