Departament de Nefrologia, Hospital Universitari de Bellvitge. IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Am J Pathol. 2010 Apr;176(4):1696-704. doi: 10.2353/ajpath.2010.090411. Epub 2010 Feb 11.
Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of T(H)1 (interleukin IL-2, IL-3, gamma-interferon, tumor necrosis factor-alpha, lymphotoxin-alpha, lymphotoxin-beta, granulocyte-macrophage colony-stimulating factor) and T(H)2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR.
伴有间质纤维化和肾小管萎缩(SCR+IF/TA)的移植肾伴有亚临床排斥反应的患者存活率较无 IF/TA 的 SCR 患者差。为了检测 SCR+IF/TA 和 SCR 之间的差异,我们对炎症浸润(CD45、CD3、CD20、CD68)进行免疫表型分析,并使用低密度阵列确定 T(H)1(白细胞介素 IL-2、IL-3、γ干扰素、肿瘤坏死因子-α、淋巴毒素-α、淋巴毒素-β、粒细胞巨噬细胞集落刺激因子)和 T(H)2(IL-4、IL-5、IL-6、IL-10 和 IL-13)转录本的水平,以及 IL-2R(作为 T 细胞活化的标志物)在 31 例肾移植患者的方案活检标本中。在这里,我们发现,基于 IL-10 基因表达的激活以及 B 淋巴细胞在细胞环境中的浸润增加,可以区分伴有早期 IF/TA 和 SCR 的移植肾与仅伴有 SCR 的移植肾,在这两组活检中,T 细胞活化的程度相似,这一点可以通过 IL-2R mRNA 的等效水平来证明。这些结果表明,IL-10 基因表达的上调以及炎症浸润中 B 淋巴细胞比例的增加可能是 SCR 移植肾早期慢性病变的有用标志物。