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ARHGDIB and AT1R autoantibodies are differentially related to the development and presence of chronic antibody-mediated rejection and fibrosis in kidney allografts
Human Immunology ( IF 2.7 ) Pub Date : 2021-01-06 , DOI: 10.1016/j.humimm.2020.12.003
Michiel G H Betjes 1 , Kasia A Sablik 1 , Nicolle H R Litjens 1 , Henny G Otten 2 , Annelies E de Weerd 1
Affiliation  

The role of non-HLA autoantibodies in chronic-active antibody-mediated rejection (c-aABMR) of kidney transplants is largely unknown. In this study, the presence and clinical relevance of non-HLA autoantibodies using a recently developed multiplex Luminex-based assay were investigated. Patients with a kidney allograft biopsy at least 6 months after transplantation with a diagnosis of c-aABMR (n = 36) or no rejection (n = 21) were included. Pre-transplantation sera and sera at time of biopsy were tested for the presence of 14 relevant autoantibodies.

A significantly higher signal for autoantibodies against Rho GDP‐dissociation inhibitor 2 (ARHGDIB) was detected in recipients with c-aABMR as compared to recipients with no rejection. However, ARHGDIB autoantibodies did not associate with graft survival. Levels of autoantibodies against angiotensin II type 1-receptor (AT1R) and peroxisomal trans‐2‐enoyl‐CoA reductase (PECR) were increased in recipients with interstitial fibrosis in their kidney biopsy. Only the signal for AT1R autoantibody showed a linear relationship with the degree of interstitial fibrosis and was associated with graft survival.

In conclusion, anti-ARHGDIB autoantibodies are increased when c-aABMR is diagnosed but are not associated with graft survival, while higher levels of AT1R autoantibody are specifically associated with the presence of interstitial fibrosis and graft survival.



中文翻译:

ARHGDIB 和 AT1R 自身抗体与肾同种异体移植物中慢性抗体介导的排斥和纤维化的发生和存在差异相关

非 HLA 自身抗体在肾移植的慢性活性抗体介导的排斥 (c-aABMR) 中的作用在很大程度上是未知的。在这项研究中,使用最近开发的基于 Luminex 的多重检测方法研究了非 HLA 自身抗体的存在和临床相关性。移植后至少 6 个月接受同种异体肾活检并诊断为 c-aABMR(n = 36)或无排斥(n = 21)的患者被包括在内。检测移植前血清和活检时血清中 14 种相关自身抗体的存在。

与没有排斥反应的受者相比,在接受 c-aABMR 的受者中检测到针对 Rho GDP 解离抑制剂 2 (ARHGDIB) 的自身抗体的明显更高的信号。然而,ARHGDIB 自身抗体与移植物存活无关。在肾活检中出现间质纤维化的受者中,针对血管紧张素 II 1 型受体 (AT1R) 和过氧化物酶体转 2-烯酰辅酶 A 还原酶 (PECR) 的自身抗体水平升高。只有 AT1R 自身抗体的信号与间质纤维化程度呈线性关系,并与移植物存活相关。

总之,当诊断出 c-aABMR 时,抗 ARHGDIB 自身抗体会增加,但与移植物存活无关,而较高水平的 AT1R 自身抗体与间质纤维化和移植物存活的存在特异性相关。

更新日期:2021-01-29
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