Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Aliment Pharmacol Ther. 2018 Jul;48(2):219-225. doi: 10.1111/apt.14825. Epub 2018 Jun 4.
Although current American guidelines distinguish proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) from eosinophilic oesophagitis (EoE), these entities are broadly similar. While two microarray studies showed that they have similar transcriptomes, more extensive RNA sequencing studies have not been done previously.
To determine whether RNA sequencing identifies genetic markers distinguishing PPI-REE from EoE.
We retrospectively examined 13 PPI-REE and 14 EoE biopsies, matched for tissue eosinophil content, and 14 normal controls. Patients and controls were not PPI-treated at the time of biopsy. We did RNA sequencing on formalin-fixed, paraffin-embedded tissue, with differential expression confirmation by quantitative polymerase chain reaction (PCR). We validated the use of formalin-fixed, paraffin-embedded vs RNAlater-preserved tissue, and compared our formalin-fixed, paraffin-embedded EoE results to a prior EoE study.
By RNA sequencing, no genes were differentially expressed between the EoE and PPI-REE groups at the false discovery rate (FDR) ≤0.01 level. Compared to normal controls, 1996 genes were differentially expressed in the PPI-REE group and 1306 genes in the EoE group. By less stringent criteria, only MAPK8IP2 was differentially expressed between PPI-REE and EoE (FDR = 0.029, 2.2-fold less in EoE than in PPI-REE), with similar results by PCR. KCNJ2, which was differentially expressed in a prior study, was similar in the EoE and PPI-REE groups by both RNA sequencing and real-time PCR.
Eosinophilic oesophagitis and PPI-REE have comparable transcriptomes, confirming that they are part of the same disease continuum.
尽管目前的美国指南区分了质子泵抑制剂反应性食管嗜酸性粒细胞增多症（PPI-REE）和嗜酸性食管炎（EoE），但这两种疾病具有广泛的相似性。虽然两项微阵列研究表明它们具有相似的转录组，但之前尚未进行更广泛的 RNA 测序研究。
确定 RNA 测序是否能识别区分 PPI-REE 与 EoE 的遗传标记。
我们回顾性地检查了 13 例 PPI-REE 和 14 例 EoE 活检组织，这些组织的组织嗜酸性粒细胞含量相匹配，还有 14 例正常对照。在活检时，患者和对照均未接受 PPI 治疗。我们对福尔马林固定、石蜡包埋的组织进行了 RNA 测序，并通过定量聚合酶链反应（PCR）进行了差异表达的确认。我们验证了福尔马林固定、石蜡包埋与 RNAlater 保存组织的使用，并将我们的福尔马林固定、石蜡包埋的 EoE 结果与之前的 EoE 研究进行了比较。
通过 RNA 测序，在错误发现率（FDR）≤0.01 水平，EoE 和 PPI-REE 组之间没有基因存在差异表达。与正常对照组相比，PPI-REE 组有 1996 个基因差异表达，EoE 组有 1306 个基因差异表达。通过较不严格的标准，仅 MAPK8IP2 在 PPI-REE 和 EoE 之间存在差异表达（FDR = 0.029，EoE 中比 PPI-REE 少 2.2 倍），PCR 也得到了类似的结果。在之前的研究中差异表达的 KCNJ2，在 EoE 和 PPI-REE 组中通过 RNA 测序和实时 PCR 均显示相似。
嗜酸性食管炎和 PPI-REE 具有相似的转录组，证实它们是同一疾病连续体的一部分。
