Estudo da resposta imunológica à infecção pelo Helicobacter pylori: comparação entre crianças e adultos

Abstract

Helicobacter pylori infection is acquired in childhood and may persist lifelong and causes severe diseases such as peptic ulcer and distal gastric carcinoma in adulthood. The immune events that occur in childhood may be crucial to determine the susceptibility to the infection and the outcome to the severe H. pylori-associated diseases in adults. Therefore, we evaluated the histology, the mean levels of cytokines, assayed by ELISA, and the number of Foxp3 cells by immunohistochemistry in the gastric mucosa of 245 children (142 H. pylori-negative and 103 H. pylori-positive) and 140 adults (40 H. pylori-negative and 100 H. pylori-positive). The degree of mononuclear and polymorphonuclear cells was significantly higher in the gastric mucosa of infected children and adults than in that of the H. pylori-negative groups, respectively. Also, the gastric mean levels of all cytokines evaluated were significantly higher in the H. pylori-positive children and adults than in the non-infected groups, respectively. Otherwise, significant differences in the gastric levels of the cytokines were observed between H. pylori-positive the children and the adults. The gastric levels of cytokine of the innate immune response (IL-1, IL-6 and TNF-) as well as of those linked to Treg (IL-10 and TGF-) and Th2 (IL-4) cell commitments were significantly higher in children than in adults. The proportion of gastric Foxp3 cells was also significantly higher in the children than in the adults. Otherwise, the gastric concentration of cytokines linked to Th1 (IL-2, IL-12p70 e IFN-) and Th17 (IL-1, IL17A, and IL-23) cells was higher in adults than in children. When the H. pylori-positive group was stratified according to the age, the gastric levels of IL-2, IFN- and IL17A increased with increasing age in children, whereas in adults the levels of IL-2, IL-12-p70, and IFN- decreased with increasing age. The decrease of the IFN- levels was more pronounced in patients over 55 years of age. Because IL-2 participates in the differentiation of Th1 and Treg cells and it has been demonstrated that IL2-330 T/G polymorphism might be functional, we also evaluated the associations between the presence of the polymorphism and risk of H. pylori infection in a group of 150 blood donors, and showed an inverse association between the two variables. In order to investigate the effect of the polymorphism on the serum concentration of IL-2 as well as of cytokines related to Th1 and Treg cells, 100 children were also evaluated. The serum levels of IL-2 were significantly higher in carriers of the TG or GG genotypes than in those harboring the wild genotype (TT). The serum levels of IL-10 and TGF-1 were higher in H. pylori-positive children but not in adults carrying the polymorphic genotypes than in the carriers of the wild genotype. However, in the infected adults, the polymorphic genotypes associated with increased levels of IFN-, finding not observed in the children. In conclusion, the results of the present study demonstrated that the immune response to the H. pylori infection varies according to the age, which may explain, at least in part, differences such as an increased susceptibility to the infection in childhood, and a more pronounced gastric lesions and an augmented prevalence of the severe diseases associated to the infection, peptic ulcer and gastric carcinoma, in adulthood.