The association between human leukocyte antigen eplet mismatches, de novo donor-specific antibodies, and the risk of acute rejection in pediatric kidney transplant recipients
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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DOI：
10.1007/s00467-020-04474-x
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发表时间：
2020-02-17
影响因子：
3
通讯作者：
Wong, Germaine
中科院分区：
文献类型：
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作者：
Sharma, Ankit;Taverniti, Anne;Wong, Germaine
背景 HLA I 类和 II 类 eplet 错配、从头供体特异性抗体 (dnDSA) 发育以及儿童期移植后急性排斥反应之间的纵向关系尚不清楚。方法 回顾性计算 2005 年至 2015 年间在澳大利亚单一中心移植的每对供体/受体对 HLA I 类和 II 类基因座的 Eplet 错配情况。进行逻辑回归分析以确定 eplet 不匹配的数量、dnDSA 和急性排斥反应之间的关联。结果 该队列由 59 名儿童（0-18 岁）组成，他们接受了第一次同种异体肾移植，并随访中位（四分位距）4.5（+/- 2.6）年。总体而言，32% (19/59) 发生了 dnDSA（I 类 3% (2/59)，II 类 14% (8/59)，I 类和 II 类 15% (9/59)），24% (14/59) 发生了经活检证实的急性排斥反应。 I 类和 II 类 eplet 不匹配的每增加一个单位，对应于 I 类（比值比 (OR) 1.22，95% CI 1.07-1.39，p < 0.01）和 II 类（OR 1.06，95% CI 1.01-1.11，p = 0.02）dnDSA 发展风险的增加。与未接受 dnDSA 的受者相比，I 类和 II 类 dnDSA 与急性细胞排斥风险增加相关（I 类：OR 5.87，95% CI 0.99-34.94，p = 0.05；II 类：OR 12.00，95% CI 1.25-115.36，p = 0.03）和急性抗体介导的排斥（I 类：OR 25.67，95% CI 3.54-186.10，p < 0.01；II 级：OR 9.71，95% CI 1.64-57.72，p = 0.01）。结论 HLA I 类或 II 类 eplet 错配数量的增加与 dnDSA 的发生有关。与未患有 dnDSA 的儿童相比，患有 dnDSA 的儿童也更容易出现急性排斥反应。
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.