Gastric Mucosal Immune Profiling and Dysregulation in Idiopathic Gastroparesis.
Gastric Mucosal Immune Profiling and Dysregulation in Idiopathic Gastroparesis.
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DOI：
10.14309/ctg.0000000000000349
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发表时间：
2021-05-12
影响因子：
3.6
通讯作者：
Habtezion A
中科院分区：
文献类型：
--
作者：
Gottfried-Blackmore A;Namkoong H;Adler E;Martin B;Gubatan J;Fernandez-Becker N;Clarke JO;Idoyaga J;Nguyen L;Habtezion A
目前尚不清楚免疫扰动如何影响特发性胃轻瘫的发病机制，特发性胃轻瘫是一种普遍存在的胃功能性疾病，缺乏动物模型。一些研究已经注意到与胃轻瘫相关的胃深部肌肉层的免疫特征改变，但缺乏可通过内窥镜观察到的粘膜层的数据。我们假设特发性胃轻瘫的胃十二指肠粘膜存在免疫失调，并且特定的免疫特征与胃轻瘫的临床参数相关。在这项横断面前瞻性病例对照研究中，采用常规内窥镜活检，通过流式细胞术、多细胞因子阵列以及胃和十二指肠球部 3 个节段的基因表达进行综合免疫分析。还探讨了免疫终点与胃轻瘫临床参数的关联。胃粘膜显示出不同免疫特征的巨大区域差异。此外，胃轻瘫患者的先天性和适应性免疫细胞增加了数倍。各种免疫细胞类型与疾病持续时间、质子泵抑制剂剂量和胃排空延迟呈正相关。这项初步观察性研究表明，特发性胃轻瘫患者的胃粘膜存在免疫区室化，白细胞浸润水平存在显着的免疫失调，并延伸至十二指肠。选择的免疫细胞，例如巨噬细胞，可能与胃轻瘫的临床病理特征相关。这项工作支持进一步的粘膜研究，以增进我们对胃轻瘫病理生理学的理解。
It is unclear how immune perturbations may influence the pathogenesis of idiopathic gastroparesis, a prevalent functional disorder of the stomach which lacks animal models. Several studies have noted altered immune characteristics in the deep gastric muscle layer associated with gastroparesis, but data are lacking for the mucosal layer, which is endoscopically accessible. We hypothesized that immune dysregulation is present in the gastroduodenal mucosa in idiopathic gastroparesis and that specific immune profiles are associated with gastroparesis clinical parameters. In this cross-sectional prospective case-control study, routine endoscopic biopsies were used for comprehensive immune profiling by flow cytometry, multicytokine array, and gene expression in 3 segments of the stomach and the duodenal bulb. Associations of immune endpoints with clinical parameters of gastroparesis were also explored. The gastric mucosa displayed large regional variation of distinct immune profiles. Furthermore, several-fold increases in innate and adaptive immune cells were found in gastroparesis. Various immune cell types showed positive correlations with duration of disease, proton pump inhibitor dosing, and delayed gastric emptying. This initial observational study showed immune compartmentalization of the human stomach mucosa and significant immune dysregulation at the level of leukocyte infiltration in idiopathic gastroparesis patients that extends to the duodenum. Select immune cells, such as macrophages, may correlate with clinicopathological traits of gastroparesis. This work supports further mucosal studies to advance our understanding of gastroparesis pathophysiology.