Eplet mismatches associated with de novo donor-specific HLA antibody in pediatric kidney transplant recipients.
Eplet mismatches associated with de novo donor-specific HLA antibody in pediatric kidney transplant recipients.
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DOI：
10.1007/s00467-021-05078-9
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Garonzik-Wang J
中科院分区：
文献类型：
--
作者：
Charnaya O;Jones J;Philogene MC;Chiang PY;Segev DL;Massie AB;Garonzik-Wang J
在首次移植时优化氨基酸(Eplet)组织相容性可降低发生供者特异性抗体(DnDSA)的风险，并可能改善儿童肾移植受者(KTR)的长期移植物存活率。我们对儿童KTR和他们各自的供者进行了回顾性分析，以确定最常见的与dnDSA形成相关的eplet。Eplet错配分析在125对儿科KTR-供者对(2006-2018年)中进行。我们确定了每个错配的发生率，并量化了每个错配的暴露患者发生dnDSA的百分比。受者平均年龄为14岁(IQR 8-17)，种族分布中黑人占42%，高加索人占48%，中东人占5.6%。受者种族差异显著，黑人82例(IQR58-98)，白人60例(IQR44-81)，其他66例(IQR61-76)，p=0.002。44%的患者在中位数37.1个月后出现dnDSA。与dnDSA−患者相比，dnDSA+患者的中位肺负荷较高，(IQR46-83)比77(IQR56-98)，p=0.012。DnDSA最常见的靶点是I类中表达的HLAA*11和A2，II类中表达的HLADQ6和DQA5。最常见的错配Eplet不是最容易导致dnDSA形成的。在种族多元化的人群中，只有一小部分eplet与抗体形成有关。单凭Eplet负荷不足以替代Eplet的免疫原性。这些发现表明，有必要优化供者选择和分配的精确度，以改善长期移植结果。
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. 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. 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. In a racially diverse population, only a subset of eplets were 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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DOI：
10.2215/cjn.10860917
发表时间：
2018-05-07
影响因子：
9.8
作者：
Leeaphorn, Napat;Pena, Jeremy Ryan A.;Cardarelli, Francesca
通讯作者：
Cardarelli, Francesca
影响因子：
0.8
作者：
Kazley, Abby S.;Hund, Jessica Jordan;Baliga, Prabhakar
通讯作者：
Baliga, Prabhakar
影响因子：
3.1
作者：
Tagliamacco, Augusto;Cioni, Michela;Nocera, Arcangelo
通讯作者：
Nocera, Arcangelo
影响因子：
3
作者：
Sharma, Ankit;Taverniti, Anne;Wong, Germaine
通讯作者：
Wong, Germaine
影响因子：
1.3
作者：
Sypek, Matthew P.;Hiho, Steve;Kausman, Joshua
通讯作者：
Kausman, Joshua