Pearl Meghan H, Grotts Jonathan, Rossetti Maura, Zhang Qiuheng, Gjertson David W, Weng Patricia, Elashoff David, Reed Elaine F, Tsai Chambers Eileen
Department of Pediatrics, Division of Pediatric Nephrology, University of California, Los Angeles, Los Angeles, California, USA.
Department of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, California, USA.
Kidney Int Rep. 2018 Dec 21;4(4):541-550. doi: 10.1016/j.ekir.2018.12.011. eCollection 2019 Apr.
Angiotensin II type 1 receptor antibody (AT1R-Ab), is a non-human leukocyte antigen (HLA) antibody implicated in poor renal allograft outcomes, although its actions may be mediated through a different pathway than HLA donor-specific antibodies (DSAs). Our aim was to examine serum cytokine profiles associated with AT1R-Ab and distinguish them from those associated with HLA DSA in serially collected blood samples from a cohort of pediatric renal transplant recipients.
Blood samples from 65 pediatric renal transplant recipients drawn during the first 3 months posttransplant, at 6, 12, and 24 months posttransplant, and during suspected episodes of kidney transplant rejection were tested for AT1R-Ab, HLA DSA, and a panel of 6 cytokines (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-8, IL-1β, IL-6, and IL-17). Associations between antibodies and cytokines were evaluated.
AT1R-Ab, but not HLA DSA, was associated with elevations in TNF-α, IFN-γ, IL-8, IL-1β, IL-6, and IL-17. This relationship remained significant even after controlling for relevant clinical factors and was consistent across all time points. In contrast to HLA DSA, AT1R-Ab was associated with elevations in vascular inflammatory cytokines in the first 2 years posttransplant.
This profile of vascular cytokines may be informative for clinical monitoring and designing future studies to delineate the distinct pathophysiology of AT1R-Ab-mediated allograft injury in kidney transplantation.
血管紧张素II 1型受体抗体（AT1R-Ab）是一种非人类白细胞抗原（HLA）抗体，与肾移植预后不良有关，尽管其作用可能通过与HLA供体特异性抗体（DSA）不同的途径介导。我们的目的是在一组儿科肾移植受者的系列采集血样中，检测与AT1R-Ab相关的血清细胞因子谱，并将其与与HLA DSA相关的细胞因子谱区分开来。
对65名儿科肾移植受者在移植后前3个月、移植后6个月、12个月和24个月以及疑似肾移植排斥发作期间采集的血样进行AT1R-Ab、HLA DSA和一组6种细胞因子（肿瘤坏死因子[TNF]-α、干扰素[IFN]-γ、白细胞介素[IL]-8、IL-1β、IL-6和IL-17）检测。评估抗体与细胞因子之间的关联。
AT1R-Ab而非HLA DSA与TNF-α、IFN-γ、IL-8、IL-1β、IL-6和IL-17升高有关。即使在控制相关临床因素后，这种关系仍然显著，并且在所有时间点都是一致的。与HLA DSA不同，AT1R-Ab与移植后前2年血管炎性细胞因子升高有关。
这种血管细胞因子谱可能有助于临床监测，并为未来研究设计提供信息，以阐明肾移植中AT1R-Ab介导的移植肾损伤的独特病理生理学。
