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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.
Pediatric Nephrology ( IF 3 ) Pub Date : 2020-02-17 , DOI: 10.1007/s00467-020-04474-x
Ankit Sharma 1, 2 , Anne Taverniti 1 , Nicole Graf 3 , Armando Teixeira-Pinto 1, 2 , Joshua R Lewis 1, 4, 5 , Wai H Lim 5, 6 , Stephen I Alexander 1 , Anne Durkan 1 , Jonathan C Craig 1, 2, 7 , Germaine Wong 1, 2
Affiliation  

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.

中文翻译:

小儿肾移植受者中人白细胞抗原小片段错配,从头供体特异性抗体与急性排斥反应的风险之间的关联。

背景技术HLA I类和II类eplet错配,新生供体特异性抗体(dnDSA)发育以及儿童移植后的急性排斥反应之间的纵向关系尚不清楚。方法回顾性分析2005年至2015年间在单个澳大利亚中心移植的每个供体/受体对的HLA I级和II级基因座的表位失配。进行logistic回归分析以确定eplet不匹配数,dnDSA和急性排斥反应之间的关联。结果该队列包括59名儿童(0-18岁),他们接受了首次同种异体肾移植,并接受了中位(四分位间距)4.5(±2.6)岁的随访。总体而言,有32%(19/59)开发了dnDSA(I类3%(2/59),II类14%(8/59),I类和II类15%(9/59)),24%(14/59)的患者经活检证实为急性排斥反应。I和II类eplet不匹配的每增加一个单位,对应于I类(优势比(OR)1.22,95%CI 1.07-1.39,p <0.01)和II类(OR 1.06,95%CI 1.01-)的风险增加。 1.11,p = 0.02)dnDSA开发。与没有dnDSA的接受者相比,I和II类dnDSA与增加急性细胞排斥风险的作用方向相关(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反应(I类:OR 25.67,95%CI 3.54-186.10,p <0.01; II类:OR 9.71,95%CI 1.64-57.72,p = 0.01) 。结论HLA I类或II类HLA错配越来越多与dnDSA的发展有关。
更新日期:2020-02-17
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