Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, Rotterdam, the Netherlands.
Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, Rotterdam, the Netherlands.
Hum Immunol. 2021 Feb;82(2):89-96. doi: 10.1016/j.humimm.2020.12.003. Epub 2021 Jan 6.
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.
非 HLA 自身抗体在慢性活动性抗体介导的排斥反应（c-aABMR）中的作用在很大程度上尚不清楚。在这项研究中，使用最近开发的多重 Luminex 基于测定法研究了非 HLA 自身抗体的存在及其临床相关性。纳入了至少在移植后 6 个月进行了肾移植活检且诊断为 c-aABMR（n=36）或无排斥反应（n=21）的患者。在移植前和活检时的血清中检测了 14 种相关自身抗体的存在情况。与无排斥反应的受者相比，c-aABMR 受者中 Rho GDP 解离抑制剂 2（ARHGDIB）自身抗体的信号显著更高。然而，ARHGDIB 自身抗体与移植物存活率无关。在其肾活检中存在间质纤维化的受者中，抗血管紧张素 II 型 1 受体（AT1R）和过氧化物酶体反式 2-烯酰辅酶 A 还原酶（PECR）的自身抗体水平增加。仅 AT1R 自身抗体的信号与间质纤维化的程度呈线性关系，并且与移植物存活率相关。总之，当诊断出 c-aABMR 时，抗 ARHGDIB 自身抗体增加，但与移植物存活率无关，而 AT1R 自身抗体水平升高则与间质纤维化的存在和移植物存活率相关。
