Shaw Brian I, Ochoa Alejandro, Chan Cliburn, Nobuhara Chloe, Gbadegesin Rasheed, Jackson Annette M, Chambers Eileen T
Department of Surgery, Duke University, Durham, NC.
Department of Biostatistics and Bioinformatics, Duke University, Durham, NC.
Transplant Direct. 2021 Aug 26;7(10):e748. doi: 10.1097/TXD.0000000000001201. eCollection 2021 Oct.
Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mechanisms of disease recurrence remain elusive.
We performed a retrospective review of the Scientific Registry of Transplant Recipients to determine the association of specific HLA recurrence of FSGS. Kidney transplants recipients under the age of 19 who were diagnosed with FSGS, who were transplanted after January 1, 2000, and who had complete HLA data were included in the study. We performed simple logistic regression on all HLA A, B, C, DR, and DQ represented in the dataset and FSGS recurrence and then determined those associated with recurrence using the Benjamini-Hochberg method for multiple comparisons. For those HLAs that were associated with recurrence, we further determined the effect of matching recipient and donor HLA with recurrence.
HLA DR7, DR53, DQ2, DR52, and DQ7 were associated with increased or decreased risk of recurrent disease after transplantation. We identified a risk haplotype consisting of HLA-DR7, DR53, and DQ2 that was consistently associated with an increased risk of recurrence (odds ratio 1.91; 95% confidence interval, 1.44-2.54, < 0.001). We also found that donor/recipient concordance for HLA-DQ7 was associated with a decreased risk of recurrence (odds ratio 0.42; 95% confidence interval, 0.37-0.53, = 0.009).
HLA profiles may be used for risk stratification of recurrence of FSGS in pediatric kidney transplant recipients and deserves further study.
肾移植后复发性局灶节段性肾小球硬化（FSGS）是原发性FSGS儿童患者同种异体移植失败的主要原因。尽管目前的研究集中在FSGS的病理生理学上，但疾病复发的常见病因和机制仍然难以捉摸。
我们对移植受者科学注册库进行了回顾性研究，以确定FSGS特异性HLA复发的相关性。研究纳入了2000年1月1日以后接受移植、确诊为FSGS、年龄在19岁以下且有完整HLA数据的肾移植受者。我们对数据集中所有代表的HLA A、B、C、DR和DQ与FSGS复发进行了简单逻辑回归，然后使用Benjamini-Hochberg多重比较方法确定与复发相关的因素。对于那些与复发相关的HLA，我们进一步确定供体和受体HLA匹配对复发的影响。
HLA DR7、DR53、DQ2、DR52和DQ7与移植后疾病复发风险的增加或降低相关。我们确定了一个由HLA-DR7、DR53和DQ2组成的风险单倍型，其始终与复发风险增加相关（优势比1.91；95%置信区间，1.44-2.54，P<0.001）。我们还发现HLA-DQ7的供体/受体一致性与复发风险降低相关（优势比0.42；95%置信区间，0.37-0.53，P=0.009）。
HLA谱可用于小儿肾移植受者FSGS复发的风险分层，值得进一步研究。
