Local and systemic immune and inflammatory responses to Helicobacter pylori strains

Abstract

Colonization with Helicobacter pylori eventuates in varied clinical outcomes, which relate to both bacterial and host factors. Here we examine the relationships between cagA status, serum and gastric juice antibody responses, and gastric inflammation in dyspeptic patients. Serum, gastric juice, and gastric biopsy specimens were obtained from 89 patients undergoing endoscopy. H. pylori colonization and cagA status were determined by histology, culture, and PCR methods, and acute inflammation and chronic inflammation in the gastric mucosa were scored by a single pathologist. Serum and gastric juice antibodies to H. pylori whole-cell and CagA antigens were determined by enzyme-linked immunosorbent assay. Relationships between variables were sequentially analyzed using univariate and multivariate statistical methods. Of the 89 subjects, 62 were colonized by H. pylori. By univariate analyses, levels of serum immunoglobulin G (IgG) and IgA and gastric juice IgA antibodies against whole-cell and CagA antigens each were significantly higher in the H. pylori-positive group than in the H. pylori-negative group (P<0.001). H. pylori and CagA sero-positivities were both significantly associated with enhanced inflammation in gastric antrum and body (P<0.02). The presence of gastric juice antibodies to H. pylori antigens was associated with more severe gastric inflammation. However, in multivariate analyses, only the presence of serum antibodies against CagA and, to a lesser extent, whole-cell antigens remained significantly associated with acute and chronic inflammation in antrum and body (P<0.05). Thus, serum antibody response to CagA correlates with severity of gastric inflammation. Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response.

FIG. 1.

Comparative antibody responses to H. pylori and CagA antigens in patients undergoing gastric biopsy. (Panel I) Serum IgG antibody responses to H. pylori whole-cell antigen. (Panel II) Serum IgG responses to CagA antigen. (Panel III) Gastric juice IgA responses to whole-cell antigen. (Panel IV) Gastric juice IgA responses to CagA antigen. Group A represents H. pylori-negative patients (n = 27) and H. pylori-positive patients (n = 62). Group B represents CagA PCR-negative patients (n = 23) and CagA PCR-positive patients (n = 39). Group C represents patients CagA negative by serology (n = 30) and CagA positive by serology (n = 32). Group D represents patients CagA negative by PCR and serology (n = 19) and CagA positive by PCR and serology (n = 28).