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. 1998 Aug;43(2):168–175. doi: 10.1136/gut.43.2.168

Systemic and local immune responses against Helicobacter pylori urease in patients with chronic gastritis: distinct IgA and IgG productive sites

S Futagami 1, H Takahashi 1, Y Norose 1, M Kobayashi 1
PMCID: PMC1727212  PMID: 10189839

Abstract

Background—Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pylori infected patients. 
Aims—To analyse the relation between systemic and local humoral immune responses to H pylori urease and grades of chronic gastritis. 
Patients—Seventy five patients with chronic gastritis associated with H pylori infection were classified into three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent; or III, atrophic gastritis, active). 
Methods—Anti-H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis. 
Results—In the sera of patients with grade I gastritis, weak IgG but relatively strong IgA responses to H pylori urease were observed; dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy. 
Conclusions—Purified H pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis of H pylori infection. 



Keywords: Helicobacter pylori; urease; chronic gastritis; B lymphocytes; antibody production; local immunity

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Figure 1 .

Figure 1

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H pylori urease specific IgG and IgA responses in sera. Horizontal bars represent median values. Horizontal lines indicate cut off levels used in the assay. 


Figure 2 .

Figure 2

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H pylori urease heavy chain (62 kDa) specific IgG, IgA, and SC responses in the gastric juice of patients. Lanes A-C, grade II gastritis; lanes D-F, grade III gastritis with haemorrhagic erosions found endoscopically; lane G, duodenal ulcer (active stage). Lanes A,D, IgG; lanes B,E, IgA; lanes C,F,G, SC. 


Figure 3 .

Figure 3

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H pylori urease specific IgG, IgA, and SC responses in gastric tissue. Horizontal bars represent median values. Horizontal lines indicate cut off levels used in the assay. 


Figure 4 .

Figure 4

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Immunohistochemical analysis of H pylori urease specific humoral responses. (A) Localisation of H pylori and H pylori urease in the stomach of a patient with grade III gastritis (enzyme immunohistochemistry with monoclonal H pylori urease specific antibody; Meyer's haematoxylin, original magnification ×160); a higher maginification (×800) of the boxed area indicated in the left upper corner is shown in the left lower corner. (B) Distribution of H pylori urease specific antibody producing B lymphocytes (plasma cells) in the same tissue (enzyme immunohistochemistry with purified H pylori urease and monoclonal H pylori urease specific antibody; methyl green, original magnification ×150); LF, lymphoid follicle. (C) Localisation of mononuclear cells in the same tissue (haematoxylin and eosin, original magnification ×150). (D) Localisation of H pylori and H pylori urease indicated by arrows in the stomach of a patient with grade II gastritis (enzyme immunohistochemistry with monoclonal H pylori urease specific antibody; Alcian blue, original magnification ×160); a higher magnification (×640) of the boxed area indicated in the right lower corner is shown in the left upper corner. (E) Distribution of H pylori urease specific B cells in the stomach from the same patient (enzyme immunohistochemistry with purified H pylori urease and monoclonal H pylori urease specific antibody; Meyer's haematoxylin, original magnification ×250). (F) Distribution of H pylori urease specific plasma cells in the stomach of a patient with grade I gastritis (enzyme immunohistochemistry with purified H pylori urease and monoclonal H pylori urease specific antibody; Meyer's haematoxylin, original magnification ×125). (G) Detection of H pylori urease specific B cells in the duodenal bulb from the same patient with grade I gastritis bearing duodenitis (enzyme immunohistochemistry with purified H pylori urease and monoclonal H pylori urease specific antibody; Meyer's haematoxylin, original magnification ×200). (H) Distribution of IgA producing B cells in the stomach of the same patient (enzyme immunohistochemistry with antihuman IgA antibody, original magnification ×132).


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