Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA.
Division of Computational Genetics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
Kidney Int. 2016 Jan;89(1):217-25. doi: 10.1038/ki.2015.276. Epub 2016 Jan 4.
The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1-3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell-associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA-selective gene transcripts may be used as molecular markers for AMR, especially in C4d- biopsies.
抗体介导的排斥反应（AMR）的诊断标准在不断发展。在这里，我们研究了移植肾活检中不同 Banff 微血管炎症（MVI）评分的临床和分子意义。根据 MVI 评分将 356 例有临床指征的移植肾活检患者分为三组，分别为 MVI 评分为 0、1、2 或更多的组 1-3。使用代表 93 例患者的阵列评估基因表达谱。供体特异性抗 HLA 抗体的发生率从第 1 组的 25%增加到第 2 组的 36%，再增加到第 3 组的 54%。与第 2 组（3%和 15%）和第 1 组（0%和 5%）相比，第 3 组的急性和慢性 AMR 明显更频繁（15%和 35%）。与第 1 组和第 2 组相比，第 3 组的干扰素-γ和排斥反应诱导的、细胞毒性和调节性 T 细胞、自然杀伤细胞相关和供体特异性抗体（DSA）选择性转录物的基因表达谱明显增加。第 1 组和第 2 组之间的基因表达谱没有明显差异。在 C4d-第 3 组患者的活检中发现移植肾内 DSA 选择性转录物的表达增加。因此，MVI 评分≥2 与急性和慢性抗体介导的排斥反应的组织学诊断显著相关。因此，移植肾内 DSA 选择性基因转录物的增加可能被用作 AMR 的分子标志物，特别是在 C4d-活检中。
