Atrophic gastritis by Helicobacter pylori and antiparietal antibodies

Transcription

1 Rawal Medical Journal An official publication of Pakistan Medical Association Rawalpindi Islamabad branch Established 1975 Volume 36 Number 2 March- June 2011 Original Article Atrophic gastritis by Helicobacter pylori and antiparietal antibodies Batool Mutar Mahdi, Riyadh Mohamad Hassan, Basma Maki, Nahla Ghanim, Leen Ghalog Al Kindi College of Medicine, Baghdad, Iraq ABSTRACT Objective To determine if atrophic gastritis is caused by H pylori and anti parietal antibodies. Patients and Methods A total of 60 atrophic gastritis patients had their blood analyzed for CagA antibodies IgG and parietal cell antibodies using an indirect immunofluorescence technique. C-reactive protein (CRP) was also measured. Results Mean age of patients was 45.67±15.54 years. In 37 (61.6%) patients, H pylori Cag A antibody IgG was positive and in 23 (38.3 %) anti parietal cell antibody was positive (p=0.011, OR and relative risk 1). In 39 (65%) patients, atrophic gastritis was seen only in the antrum; 74.3% of them had H pylori Cag A antibody IgG positive, while 25.6 % had anti parietal cell antibody positive (p=0.000). All atrophic gastritis patients showed positive CRP. Conclusions H. pylori infection can exist with autoimmune gastritis leading to cross reactive gastric T cells activation via molecular mimicry. (Rawal Med J 2011;36:74-78). 1

2 Keywords Antiparietal antibody, atrophy, autoimmune, gastritis, Helicobacter pylori. INTRODUCTION Atrophic gastritis was first recognized in 1870 in postmortem samples of a patient with pernicious anemia. 1 Corpus atrophy due to autoimmune gastritis associated with pernicious anemia has become well known. 2 The recognition and culture of Helicobacter pylori (H pylori) has largely changed the etiology of gastritis 3 and mucosal immune responses are designed to provide local protection against infection, serve as a barrier to exclude pathogens, and initiate host responses to infection. When H pylori infects gastric epithelial cells it induces neutrophils infiltration within hours, 4 local T-cells (CD4 Th1+) activation and increase in the level of local IgG antibodies, which may damage the epithelium. 5 It had been found that gastric autoantibodies were present in H pylori positive atrophic gastritis. 6 Atrophic changes can be determined by serum markers (pepsinogen and gastrin) and parietal cell and intrinsic factor antibodies. 7 Autoimmune chronic atrophic gastritis is characterised by hypochloridria and later, pernicious anaemia. This results from lymphocytes infiltration in the gastric mucosa and destruction of parietal cells by autoreactive T cells and autoantibodies directed against gastric H + K + adenosine triphosphatase (ATPase), the proton pump, localized in the parietal cell canaliculi and H -, K - ATPase. 8 There are five potential etiologic and pathophysiologic processes fundamental to autoimmune disease: inflammation, infection, apoptosis, environmental exposure and genetics. 9 In autoimmune atrophic gastritis, H. pylori infected patients who develop gastric corpus atrophy, an increased incidence of positive parietal cell antibodies has been reported, which significantly decreases after H. pylori eradication. 10 This is due to induction of autoantibodies by H pylori next to gastric proton pump H +, K + -ATPase leading to apoptosis in the corpus mucosa and atrophy. 10 Therefore, in some individuals, genetically 2

3 predisposed to organ-specific autoimmunity due to their MHC class II haplotype, H. pylori infection plays a role in induction or exacerbation of gastric autoimmunity. 11 The objective of the study was to determine if atrophic gastritis was caused by H pylori infection or anti parietal antibodies. PATIENTS AND METHODS The study consists of 60 atrophic gastritis patients seen at Al-Kindi Teaching Hospital in Baghdad from September 2008 to May Thewere classified as atrophic gastritis by endoscopy and histopathological examination in accordance with Sydney system. 8 Patients who previously had prior helicobacter eradication therapy, drug-associated or other known gastric irritants, infective (excluding H. pylori) aetiology or pathogenic associations of bacterial, viral, parasitic, fungal and eosinophilic gastritis, lymphocytic gastritis, granulomatous gastritis (Crohn s associated, sarcoid and reactive gastritis) and radiationassociated phlegmonous gastritis were excluded from the study. In addition, subjects with history of major systemic diseases including diabetes mellitus, adrenal insufficiency, iron deficiency anemia, thyrotoxicosis, myxedema, and Hashimoto's thyroiditis were excluded. CagA antibodies Immunoglobulin G (IgG) were determined using an immmunochromatography test (Acon-USA) on serum. Parietal cell antibodies were studied using an indirect immunofluorescence technique (Euroimmune-Germany). C-reactive protein (CRP) was done qualitatively by the latex agglutination method (Plasmatic, UK). The Ethical Committee of Al-Kindi College of Medicine, Baghdad University and Al- Kindi Teaching Hospital approved the study and all samples were obtained with informed consent. Data was analyzed statistically using descriptive statistics and for inferential statistics Fisher s exact test and Chi-square tests were used. P values <0.05 were considered statistically significant. Calculations were performed using MiniTab statistical software program

4 RESULTS A total of 60 atrophic gastritis patients were included. Their mean age was ±15.54 years (range 19 to 84). Forty were males (66.6%) and the rest were females. As shown in table 1, 37 (61.6%) had H. Pylori Cag A antibody IgG positive and 23 (38.3%) had anti parietal cell antibody positive (p=0.011). The titer was 1:10 of mix isotypes (IgG, IgM and IgA). The highest titer was 1:80 in ten patients (16.6%). Level of vitamin B12 was decreased (Data is not shown). Table1. Atrophic gastritis caused by H Pylori Cag A Antibody IgG and Anti parietal cell antibody (n=60). H pylori Antibody IgG Anti parietal cell antibody Odd ratio and relative risk No. % No. % Atrophic gastritis ,*P< 0.05 *comparison between H pylori and anti parietal cell antibody. An odds ratio of 1 implies that the atrophic gastritis is equally likely in both groups and a relative risk equal to 1 implies that the atrophic gastritis is equally probable in both groups. Table 2. Different sites of gastric atrophy. Site of atrophy H pylori Antibody Anti parietal cell antibody p-value No. % No. % No. % Antrum *0.000 Corpus **>0.05 Both **>0.05 *comparison between H pylori and anti parietal cell antibody using Chi-square test. **comparison between H pylori and anti parietal cell antibody using Fisher s Exact test 4

5 Commonest site of atrophic gastritis was antrum (65%) and significantly more common (P=0.000) in H pylori positive (Table 2). Table 3. CRP in patients with atrophic gastritis. CRP with Atrophic gastritis (n=60) CRP With Antrum Atrophy (n=39) CRP With Corpus Atrophy (n=18) CRP with Both atrophy (n=3) P value No. % No. % No. % No. % *>0.05 *comparison among groups using ANOVA test. CRP was positive in 96.6% of patients with atrophic gastritis whether atrophy affected antrum (97.4%), corpus (94.4%) and both (Table 3). Table 4. Antrum atrophic gastritis according to the grade. Site Antru m atrophy (n=39) Atrophy grade H pylori Antibody Anti parietal cell antibody p-value No % No % No % 0-none mild *> *P=0.00 moderate 0 3-severe *>0.05 *comparison between H pylori and anti parietal cell antibody using Fisher s Exact test There was moderate antrum atrophy in 61.53% and due to H Pylori (83.3%) (p=0.000) while there was no significant difference in corpus and in both corpus and antrum atrophy (Tables 4, 5 and 6). 5

6 Table 5. Corpus atrophic gastritis according to the grade. Site Corpus atrophy No.=18 Atrophy grade H pylori Antibody Anti parietal cell antibody p-value No % No % No. % 0-none mild *> *>0.05 moderate 3-sever *>0.05 *comparison between H pylori and anti parietal cell antibody using Fisher s Exact test Site Antrum Corpus atrophy (n=3) DISCUSSION In agreement with previous studies 12,13 atrophic gastritis is more common in helicobacter positive than negative patients. As an atrophic change in the corpus and antrum considered separately, either H pylori positivity, verified by serology, is strongly associated with atrophic antral gastritis. There are many factors which lead to atrophic gastritis and pernicious anaemia other than H pylori. 6 Oksanen et al found that patients without pernicious anemia (normal vitamin B12 levels) had lower of H pylori antibodies due to the disappearance of H pylori infection. 6 We found no significant difference in the H pylori positive and anti parietal antibody positive patients where the site of atrophy was in the corpus. Thus, H pylori infection may equally affects the corpus same as anti parietal antibody due to molecular mimicry. 14 Table 6. Antrum and corpus atrophic gastritis according to the grade. and Atrophy grade H pylori Antibody Anti parietal cell antibody p-value No. % No. % No % 0-non mild *> *comparison between H pylori and anti parietal cell antibody using Fisher s Exact test 6

7 A relationship between atrophic antral gastritis and CagA seropositivity has been postulated. 6 In the present study, among helicobacter positive patients, CagA positively was not significantly different with atrophic gastritis in the corpus but there was a significant association with atrophic antral gastritis. In case of atrophy, there was only a significant difference with antiparietal antibody in antral atrophy and not in corpus atrophy. There are several mechanisms that explain this. Viral and bacterial super antigens bind to a specific MHC class II molecules and activate many autoreactive T cells that activate antigen presenting cells and enhancing processing and presentation of self antigens, resulting in inflammation and bystander activation of autoreactive T cells by paracrine secretion of T cell growth factor. 8 A molecular mimicry between H pylori antigens and H + K + Adenosine Triphosphatase (ATPase) in human gastric autoimmunity has also been suggested. 8,15 In addition, activation of NF-B and production of nitric oxide induce apoptosis of gastric parietal cells. 16 Other study found that APCA plays an important role in the progression of corpus atrophy after H. pylori infection. 17 It had been found that the cause of unexplained iron deficiency anemia was due to H pylori and autoimmune gastritis. 18,19 CRP was positive in most patients with H pylori infection and anti parietal antibodies. This indicates a progressive disease activity and inflammation because CRP is an acute phase proteins. Its production increases rapidly by hepatocytes during inflammation under the effect of interleukin (IL-6), tumor necrosis factor α (TNF-α), and IL-1β. 20 There is no discrepancies with other studies from our study and it can concluded that there is an association between H pylori infection and autoimmune atrophic gastritis. Correspondence: Batool Mutar Mahdi. batool1966@yahoo.com Received: January 26, 2011 Accepted: March 24,

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