Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, OH, USA.
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Nephrol Dial Transplant. 2019 Jul 1;34(7):1197-1206. doi: 10.1093/ndt/gfy125.
Up to 50% of lupus nephritis (LN) patients experience renal flares after their initial episode of LN. These flares contribute to poor renal outcomes. We postulated that intrarenal immune gene expression is different in flares compared with de novo LN, and conducted these studies to test this hypothesis.
Glomerular and tubulointerstitial immune gene expression was evaluated in 14 patients who had a kidney biopsy to diagnose LN and another biopsy at their first LN flare. Ten healthy living kidney donors were included as controls. RNA was extracted from laser microdissected formalin-fixed paraffin-embedded kidney biopsies. Gene expression was analyzed using the Nanostring nCounter® platform and validated by quantitative real-time polymerase chain reaction. Differentially expressed genes were analyzed by the Ingenuity Pathway Analysis and Panther Gene Ontology tools.
Over 110 genes were differentially expressed between LN and healthy control kidney biopsies. Although there was considerable molecular heterogeneity between LN biopsies at diagnosis and flare, for about half the LN patients gene expression from the first LN biopsy clustered with the repeated LN biopsy. However, in all patients, a set of eight interferon alpha-controlled genes had a significantly higher expression in the diagnostic biopsy compared with the flare biopsy. In contrast, nine tumor necrosis factor alpha-controlled genes had higher expression in flare biopsies.
There is significant heterogeneity in immune-gene expression of kidney tissue from LN patients. There are limited but important differences in gene expression between LN flares, which may influence treatment decisions.
多达 50%的狼疮肾炎 (LN) 患者在首次 LN 发作后会出现肾脏复发。这些复发会导致肾脏预后不良。我们推测，与初发 LN 相比，复发时肾内免疫基因表达不同，并进行了这些研究来验证这一假设。
对 14 名患者的肾小球和肾小管间质免疫基因表达进行了评估，这些患者因 LN 行肾活检，首次 LN 复发时又进行了另一次活检。纳入 10 名健康的活体供肾者作为对照。从激光微切割福尔马林固定石蜡包埋的肾活检组织中提取 RNA。使用 Nanostring nCounter®平台分析基因表达，并通过定量实时聚合酶链反应进行验证。使用 IPA 和 Panther Gene Ontology 工具分析差异表达基因。
LN 与健康对照肾活检之间有超过 110 个基因表达差异。尽管在诊断时和复发时的 LN 活检之间存在相当大的分子异质性，但对于大约一半的 LN 患者，其首次 LN 活检的基因表达与重复的 LN 活检聚类。然而，在所有患者中，一组 8 个干扰素α调控基因在诊断性活检中的表达明显高于复发性活检。相比之下，9 个肿瘤坏死因子α调控基因在复发性活检中的表达更高。
LN 患者的肾脏组织免疫基因表达存在显著异质性。LN 复发之间的基因表达存在有限但重要的差异，这可能会影响治疗决策。
