Children's Mercy Kansas City, Kansas, MO, United States.
Nemours Children's Health, Jacksonville, FL, United States.
Front Immunol. 2024 Aug 13;15:1420208. doi: 10.3389/fimmu.2024.1420208. eCollection 2024.
Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis.
This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn's disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts.
We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types.
There were common patterns among GI disorders, such as the widespread upregulation of across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation of across cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.
胃肠道组织的慢性炎症是胃肠道炎症性疾病的基础，导致组织损伤和一系列疼痛和虚弱的症状。这些疾病包括炎症性肠病（克罗恩病和溃疡性结肠炎）和嗜酸性疾病（嗜酸性食管炎和嗜酸性十二指肠炎）。胃肠道炎症性疾病常表现出重叠的症状，需要进行侵入性程序以做出准确的诊断。
本研究使用来自克罗恩病、溃疡性结肠炎、嗜酸性食管炎和嗜酸性十二指肠炎患者的外周血单核细胞，以更好地了解这些疾病患者的转录组变化，并确定外周血中潜在的活跃炎症标志物，这些标志物可能有助于诊断。对儿科患者的血液样本中的外周血单核细胞进行单细胞 RNA 测序，这些患者被诊断为胃肠道疾病，包括克罗恩病、溃疡性结肠炎、嗜酸性食管炎、嗜酸性十二指肠炎和胃肠道组织学健康的对照。
我们在 8 种免疫细胞类型中鉴定出 730 个（FDR < 0.05）胃肠道疾病患者与对照之间差异表达的基因。
胃肠道疾病之间存在共同的模式，例如细胞类型广泛上调 ，与对照相比，许多差异表达的基因在不同的胃肠道疾病中表现出不同的失调模式，包括溃疡性结肠炎患者的细胞类型上调 以及嗜酸性疾病中 Th2 相关基因的上调。这些发现表明与对照相比，胃肠道疾病患者的转录组存在重叠和独特的改变，这为哪些基因可能作为患者外周血中疾病的标志物提供了深入了解。
