Challenges and opportunities in bringing non-HLA antibody testing for post-transplant monitoring.

Frontiers in transplantation Pub Date : 2025-06-05 eCollection Date: 2025-01-01 DOI:10.3389/frtra.2025.1594241
Mary Carmelle Philogene, Inna Tchoukina, Idoia Gimferrer
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Abstract

Evidence for the contribution of non-HLA antibodies on long-term allograft outcome was suggested in early studies by Paul Terasaki and colleagues who showed worse 10-year allograft outcome in HLA identical kidney transplant recipients with a positive panel reactive antibody (PRA) as determined by the micro cytotoxicity assay, in which cells express other targets beside HLA. More recent reports have shown worse graft outcome when antibodies against non-HLA antigens were detected with HLA-donor specific antibodies (HLA-DSA), and even suggest that non-HLA antibodies may serve as precursor to development of HLA antibodies. Unfortunately, the recent studies lack reproducibility, which then leads to skepticism as to the relevance of non-HLA antibody in transplantation outcome. Consequently, routine testing for non-HLA antibody along with monitoring of HLA-DSA as part of a post-transplant immune surveillance protocol is not standard practice. The Sensitization in Transplantation: Assessment of Risk (STAR) workgroup summarized the current literature on this topic, citing differences in cohort characteristics, variability in study design, selection of sample and timepoints for testing and variability in the assays used to detect non-HLA antibodies, as reasons that impact the accurate assessment on the relevance of non-HLA antibodies. However, correlation between test results and outcome can only be determined if the assay in question is detecting the correct analyte. Therefore, here we will make the case for a plan that requires a systematic validation of high-throughput bead-based assays, to include appropriate sequence selection for non-HLA antigenic targets and quality control metrics as a first step to solving this puzzle.

将非hla抗体检测用于移植后监测的挑战和机遇。
Paul Terasaki和他的同事在早期的研究中提出了非HLA抗体对长期同种异体移植结果的贡献的证据,他们发现,在微细胞毒性试验中,具有阳性组反应性抗体(PRA)的HLA相同肾移植受者10年同种异体移植结果更差,其中细胞表达HLA以外的其他靶点。最近的报告显示,当针对非HLA抗原的抗体与HLA供体特异性抗体(HLA- dsa)一起检测时,移植物预后更差,甚至表明非HLA抗体可能是HLA抗体发展的前体。不幸的是,最近的研究缺乏可重复性,这导致了对非hla抗体在移植结果中的相关性的怀疑。因此,作为移植后免疫监测方案的一部分,常规检测非hla抗体并监测HLA-DSA并不是标准做法。移植致敏:风险评估(STAR)工作组总结了目前关于这一主题的文献,引用了队列特征的差异、研究设计的可变性、样本和测试时间点的选择以及用于检测非hla抗体的检测方法的可变性,作为影响对非hla抗体相关性准确评估的原因。然而,检测结果和结果之间的相关性只能在检测正确分析物的情况下确定。因此,在这里,我们将提出一项计划,该计划需要对高通量头颅检测进行系统验证,包括针对非hla抗原靶点的适当序列选择和质量控制指标,作为解决这一难题的第一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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