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病例报告:ATP4A突变驱动的胃神经内分泌肿瘤中提示巨细胞病毒感染及与肠道/克罗恩病相符的相同机制起源的肠道炎症。

Case Report: CMV Infection and Same Mechanism-Originated Intestinal Inflammation Compatible With Bowel/Crohn's Disease Is Suggested in ATP4A Mutated-Driven Gastric Neuroendocrine Tumors.

作者信息

Calvete Oriol, Reyes José, Benítez Javier

机构信息

Human Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.

Network of Research on Rare Diseases (CIBERER), Madrid, Spain.

出版信息

Front Med (Lausanne). 2021 Apr 6;8:553110. doi: 10.3389/fmed.2021.553110. eCollection 2021.

Abstract

Mutations in the ATP4A proton pump prevent gastric acidification and explain the chronic autoimmune gastritis scenario that conducts the gastric neuroendocrine tumor (gNET) formation. Here, we wanted to investigate the co-occurrence cytomegalovirus (CMV) infection and intestinal inflammation that presented all members of a family affected with gNET and carrying an mutation. Intestinal inflammation persisted after CMV eradication and anemia treatment. The inflammation was compatible with a ileitis/Crohn's disease and was originated by the same autoimmune mechanism described in the tumorigenesis of gNETS. The same secondary disease but no the CMV infection was observed in all members affected with gNET and carrying the ATP4A mutation. Our results suggest that the malfunction not only explained gNETs but also the co-occurring disease and opportunistic infections, which allowed to link autoimmune pathologies and gNETs in a unique mechanism. Our results open a new window to better understand not only gastric neoplasms formation but the co-occurring autoimmune disorders and the inflammatory mechanism that compose a premalignant scenario for other tumor formation. Our findings are important since contribute to describe the genetic landscape of the Inflammatory Bowel/Crohn's disease and alert clinicians to monitor patients with gastric neoplasms mediated by achlorhydria mechanisms for concomitant secondary pathologies.

摘要

ATP4A质子泵的突变会阻止胃酸分泌,并解释了导致胃神经内分泌肿瘤(gNET)形成的慢性自身免疫性胃炎情况。在此,我们想要研究一个受gNET影响且携带一种突变的家族所有成员中出现的巨细胞病毒(CMV)感染与肠道炎症的共现情况。在根除CMV和治疗贫血后,肠道炎症依然存在。这种炎症与回肠炎/克罗恩病相符,并且是由gNET肿瘤发生过程中所描述的相同自身免疫机制引发的。在所有受gNET影响且携带ATP4A突变的成员中都观察到了相同的继发性疾病,但未观察到CMV感染。我们的结果表明,该功能异常不仅解释了gNET的发生,还解释了共现疾病和机会性感染,这使得能够通过一种独特机制将自身免疫性疾病与gNET联系起来。我们的结果不仅为更好地理解胃肿瘤的形成,还为理解共现的自身免疫性疾病以及构成其他肿瘤形成癌前情况的炎症机制打开了一扇新窗口。我们的发现很重要,因为它们有助于描述炎症性肠病/克罗恩病的遗传特征,并提醒临床医生监测由胃酸缺乏机制介导的胃肿瘤患者是否伴有继发性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6e4/8055817/3db8e76adc54/fmed-08-553110-g0001.jpg

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