Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias (UIMEIP), Hospital de Pediatría, CMN Siglo-XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
PLoS One. 2013 Apr 24;8(4):e62850. doi: 10.1371/journal.pone.0062850. Print 2013.
H. pylori infection is acquired during childhood and causes a chronic inflammatory response in the gastric mucosa, which is considered the main risk factor to acquire gastric cancer (GC) later in life. More recently, infection by Epstein-Barr virus (EBV) have also been associated with GC. The role of EBV in early inflammatory responses and its relationship with H. pylori infection remains poorly studied. Here, we assessed whether EBV infection in children correlated with the stage of gastritis and whether co-infection with H. pylori affected the severity of inflammation.
METHODOLOGY/PRINCIPAL FINDINGS: 333 pediatric patients with chronic abdominal pain were studied. From them, gastric biopsies were taken and inflammation graded according to the Sydney system; peripheral blood was drawn and antibodies against EBV (IgG and IgM anti-VCA) and H. pylori (IgG anti-whole bacteria and anti-CagA) were measured in sera. We found that children infected only by EBV presented mild mononuclear (MN) and none polymorphonuclear (PMN) cell infiltration, while those infected by H. pylori presented moderate MN and mild PMN. In contrast, patients co-infected with both pathogens were significantly associated with severe gastritis. Importantly, co-infection of H. pylori CagA+/EBV+ had a stronger association with severe MN (PR 3.0) and PMN (PR 7.2) cells than cases with single H. pylori CagA+ infection.
CONCLUSIONS/SIGNIFICANCE: Co-infection with EBV and H. pylori in pediatric patients is associated with severe gastritis. Even single infections with H. pylori CagA+ strains are associated with mild to moderate infiltration arguing for a cooperative effect of H. pylori and EBV in the gastric mucosa and revealing a critical role for EBV previously un-appreciated. This study points out the need to study both pathogens to understand the mechanism behind severe damage of the gastric mucosa, which could identified children with increased risk to present more serious lesions later in life.
幽门螺杆菌感染发生在儿童时期，导致胃黏膜发生慢性炎症反应，这被认为是日后发生胃癌的主要危险因素。最近，人们还发现 Epstein-Barr 病毒（EBV）感染也与胃癌有关。EBV 在早期炎症反应中的作用及其与幽门螺杆菌感染的关系仍研究甚少。在这里，我们评估了儿童期 EBV 感染是否与胃炎的分期有关，以及与幽门螺杆菌的合并感染是否会影响炎症的严重程度。
方法/主要发现：研究了 333 例患有慢性腹痛的儿科患者。从他们身上采集胃活检组织，并根据悉尼系统对炎症进行分级；抽取外周血，并在血清中测量针对 EBV（IgG 和 IgM 抗-VCA）和幽门螺杆菌（IgG 抗全菌和抗-CagA）的抗体。我们发现，仅感染 EBV 的儿童表现为轻度单核细胞（MN）和无多形核（PMN）细胞浸润，而感染幽门螺杆菌的儿童则表现为中度 MN 和轻度 PMN。相比之下，同时感染两种病原体的患者与严重胃炎显著相关。重要的是，与单一幽门螺杆菌 CagA+感染相比，幽门螺杆菌 CagA+/EBV+的合并感染与严重 MN（PR3.0）和 PMN（PR7.2）细胞的相关性更强。
结论/意义：在儿科患者中，EBV 和幽门螺杆菌的合并感染与严重胃炎有关。即使是单一的幽门螺杆菌 CagA+菌株感染也与轻度至中度浸润有关，这表明幽门螺杆菌和 EBV 在胃黏膜中有协同作用，并揭示了 EBV 以前未被认识到的关键作用。这项研究指出需要同时研究这两种病原体，以了解导致胃黏膜严重损伤的机制，从而确定儿童中存在更高风险的人群，这些儿童日后可能会出现更严重的病变。
