The extent of HLA‐DR expression on HLA‐DR+ Tregs allows the identification of patients with clinically relevant borderline rejection

The extent of HLA‐DR expression on HLA‐DR+ Tregs allows the identification of patients with clinically relevant borderline rejection
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HLAâDR Tregs 上 HLAâDR 表达的程度可以识别具有临床相关边缘排斥反应的患者

DOI:
10.1111/tri.12032
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发表时间:
2013
影响因子:
3.1
通讯作者:
A. Steinborn
A. Steinborn
中科院分区:
医学3区
文献类型:
--
作者:
M. Schaier;N. Seissler;LE Becker;SM Schaefer;E. Schmitt;S. Meuer;F. Hug;C. Sommerer;R. Waldherr;M. Zeier;A. Steinborn

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调节性T细胞(Tregs)参与了移植后急性排斥的发生。总调节性T细胞池的抑制活性取决于其高度抑制的HLA-DR+-Treg细胞的百分比。因此,我们对非移植志愿者、终末期肾功能衰竭(ESRF)患者、因Bord-R或急性肾功能衰竭(ARF)而怀疑有排斥反应的健康肾移植患者以及临床相关的临界排斥反应(Bord-R和ARF)患者的总Treg池抑制活性和人类白细胞抗原-DR+-Tregs(MFI)-DR表达程度(MFI-DR)进行了评估。与仅有Bord-R或仅有ARF的患者相比,在临床相关的Bord-R患者中,总Treg细胞池的抑制活性完全降低。同时,这些患者DR+-Treg亚群的HLA-DR MFI显著降低,这是因为DRHigh+-Tregs的比例显著降低,而DRHigh+-Tregs被证明在总Treg池中具有最高的抑制能力。我们的研究结果清楚地表明,通过测定人类白细胞抗原DR+-Treg亚群中的人类白细胞抗原-DR MFI,可以对临床相关的Bord-R患者(Bord和ARF)和亚临床排斥或其他原因导致的移植失败患者进行高度敏感、特异和非侵入性的区分。
Regulatory T cells (Tregs) were shown to be involved into the pathogenesis of acute rejection after transplantation. The suppressive activity of the total regulatory T cell pool depends on its percentage of highly suppressive HLA‐DR+‐Treg cells. Therefore, both the suppressive activity of the total Treg pool and the extent of HLA‐DR expression of HLA‐DR+‐Tregs (MFI HLA‐DR) were estimated in non transplanted volunteers, patients with end‐stage renal failure (ESRF), healthy renal transplant patients with suspicion on rejection, due to sole histological Bord‐R or sole acute renal failure (ARF), and patients with clinically relevant borderline rejection (Bord‐R and ARF). Compared to patients with only Bord‐R or only ARF, the suppressive activity of the total Treg cell pool was exclusively reduced in patients with clinically relevant Bord‐R. In parallel, the HLA‐DR MFI of the DR+‐Treg subset was significantly decreased in these patients, due to a significantly lower proportion of DRhigh+‐Tregs, which were shown to have the highest suppressive capacity within the total Treg pool. Our findings clearly demonstrate that the determination of the HLA‐DR MFI of the HLA‐DR+‐Treg subset allows a highly sensitive, specific and non‐invasive discrimination between patients with clinically relevant Bord‐R (Bord and ARF) and patients with subclinical rejection or other causes of transplant failure.
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