Ikuse Tamaki, Ohtsuka Yoshikazu, Obayashi Naho, Jimbo Keisuke, Aoyagi Yo, Kudo Takahiro, Asaoka Daisuke, Hojo Mariko, Nagahara Akihito, Watanabe Sumio, Blanchard Thomas G, Czinn Steven J, Shimizu Toshiaki
Department of Pediatric and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Pediatr Int. 2018 May;60(5):446-454. doi: 10.1111/ped.13527. Epub 2018 May 8.
Chronic Helicobacter pylori infection in children induces lymphoid hyperplasia called nodular gastritis (NG) at the antral gastric mucosa. The aim of this study was to evaluate genes in gastric biopsy on microarray analysis, to identify molecules associated with NG on comparison with NG-negative pediatric corpus tissue and with H. pylori-infected adult tissue with atrophic gastritis (AG).
Eight pediatric and six adult H. pylori-infected patients, as well as six pediatric and six adult uninfected patients were evaluated. All infected adults had AG. NG was observed in the antrum of all eight pediatric patients and in the corpus of three patients. Adult and uninfected patients were free of NG; that is, only pediatric H. pylori-infected patients had NG. Total RNA was purified from gastric biopsy, and microarray analysis was performed to compare gene expression between groups. The three infected children with NG in both the antrum and corpus were excluded from analysis of corpus samples.
The number of genes significantly up- or downregulated (fold change >3, P < 0.01) compared with uninfected controls varied widely: 72 in pediatric antrum, 45 in pediatric corpus, 103 in adult antrum and 71 in adult corpus. Nineteen genes had significantly altered expression in the antrum of NG tissue compared with NG-negative pediatric corpus tissue and adult AG tissue. The CD20 B-cell specific differentiation antigen had the most pronounced increase. Previously described regulators of NG development were not predominantly upregulated in the NG mucosa.
CD20 overexpression may play an important role in lymphoid follicle enlargement and NG.
儿童慢性幽门螺杆菌感染会在胃窦部黏膜诱发称为结节性胃炎(NG)的淋巴样增生。本研究的目的是通过微阵列分析评估胃活检组织中的基因,通过与NG阴性的儿童胃体组织以及幽门螺杆菌感染的萎缩性胃炎(AG)成人组织进行比较,来鉴定与NG相关的分子。
评估了8名感染幽门螺杆菌的儿童患者、6名感染幽门螺杆菌的成人患者,以及6名未感染的儿童患者和6名未感染的成人患者。所有感染的成人都患有AG。在所有8名儿童患者的胃窦部以及3名患者的胃体部观察到了NG。成人和未感染患者没有NG;也就是说,只有感染幽门螺杆菌的儿童患者有NG。从胃活检组织中纯化总RNA,并进行微阵列分析以比较各组之间的基因表达。在胃体样本分析中排除了3名胃窦部和胃体部均有NG的感染儿童。
与未感染对照组相比,显著上调或下调(倍数变化>3,P<0.01)的基因数量差异很大:儿童胃窦部有72个,儿童胃体部有45个,成人胃窦部有103个,成人胃体部有71个。与NG阴性的儿童胃体组织和成人AG组织相比,19个基因在NG组织的胃窦部表达有显著改变。CD20 B细胞特异性分化抗原的增加最为明显。先前描述的NG发育调节因子在NG黏膜中并未主要上调。
CD20的过表达可能在淋巴滤泡增大和NG中起重要作用。