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The association between human leukocyte antigen eplet mismatches, de novo donor-specific antibodies, and the risk of acute rejection in pediatric kidney transplant recipients

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ARTICLE DOWNLOAD

The association between human leukocyte antigen eplet mismatches, de novo donor-specific antibodies, and the risk of acute rejection in pediatric kidney transplant recipients

10$

Ankit Sharma, Anne Taverniti, Nicole Graf, Armando Teixeira-Pinto, Joshua R. Lewis, Wai H. Lim, Stephen I. Alexander, Anne Durkan, Jonathan C. Craig & Germaine Wong 

Abstract

Background

The longitudinal relationship between HLA class I and II eplet mismatches, de novo donor-specific antibodies (dnDSA) development, and acute rejection after transplantation in childhood is unknown.

Methods

Eplet mismatches at HLA class I and II loci were calculated retrospectively for each donor/recipient pair transplanted between 2005 and 2015 at a single Australian center. Logistic regression analyses were conducted to determine the association between the number of eplet mismatches, dnDSA, and acute rejection.

Results

The cohort comprised 59 children (aged 0–18 years) who received their first kidney allograft and were followed for median (interquartile range) 4.5 (± 2.6) years. Overall, 32% (19/59) developed dnDSA (class I 3% (2/59), class II 14% (8/59), 15% class I and II (9/59)), and 24% (14/59) developed biopsy-proven acute rejection. Every unit increase in class I and II eplet mismatches corresponded to an increase in risk of class I (odds ratio (OR) 1.22, 95% CI 1.07–1.39, p < 0.01) and class II (OR 1.06, 95% CI 1.01–1.11, p = 0.02) dnDSA development. Compared with recipients without dnDSA, class I and II dnDSA were associated with direction of effect towards increased risk of acute cellular rejection (class I: OR 5.87, 95% CI 0.99–34.94, p = 0.05; class II: OR 12.00, 95% CI 1.25–115.36, p = 0.03) and acute antibody-mediated rejection (class I: OR 25.67, 95% CI 3.54–186.10, p < 0.01; class II: OR 9.71, 95% CI 1.64–57.72, p = 0.01).

Conclusions

Increasing numbers of HLA class I or II eplet mismatches were associated with the development of dnDSA. Children who developed dnDSA were also more likely to develop acute rejection compared with children without dnDSA.

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Year 2020
Language English
Format PDF
DOI 10.1007/s00467-020-04474-x