Sharma Ankit, Taverniti Anne, Graf Nicole, Teixeira-Pinto Armando, Lewis Joshua R, Lim Wai H, Alexander Stephen I, Durkan Anne, Craig Jonathan C, Wong Germaine
Centre for Kidney Research, Children's Hospital at Westmead, Sydney, Australia.
School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
Pediatr Nephrol. 2020 Jun;35(6):1061-1068. doi: 10.1007/s00467-020-04474-x. Epub 2020 Feb 17.
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.
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.
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).
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.
儿童移植后，HLA I类和II类表位错配、新发供者特异性抗体（dnDSA）产生与急性排斥反应之间的纵向关系尚不清楚。
回顾性计算2005年至2015年在澳大利亚单一中心进行移植的每对供者/受者的HLA I类和II类基因座的表位错配情况。进行逻辑回归分析以确定表位错配数量、dnDSA与急性排斥反应之间的关联。
该队列包括59名接受首次肾移植的儿童（年龄0 - 18岁），中位随访时间（四分位间距）为4.5（±2.6）年。总体而言，32%（19/59）产生了dnDSA（I类3%（2/59），II类14%（8/59），I类和II类15%（9/59）），24%（14/59）发生了活检证实的急性排斥反应。I类和II类表位错配每增加一个单位，I类dnDSA产生风险增加（比值比（OR）1.22，95%置信区间1.07 - 1.39，p < 0.01），II类dnDSA产生风险增加（OR 1.06，95%置信区间1.01 - 1.11，p = 0.02）。与未产生dnDSA的受者相比，I类和II类dnDSA与急性细胞性排斥反应风险增加的效应方向相关（I类：OR 5.87，95%置信区间0.99 - 34.94，p = 0.05；II类：OR 12.00，95%置信区间1.25 - 115.36，p = 0.03）以及急性抗体介导的排斥反应（I类：OR 25.67，95%置信区间3.54 - 186.10，p < 0.01；II类：OR 9.71，95%置信区间1.64 - 57.72，p = 0.01）。
HLA I类或II类表位错配数量增加与dnDSA的产生相关。与未产生dnDSA的儿童相比，产生dnDSA的儿童也更有可能发生急性排斥反应。
