Autoimmune gastritis (AIG) is a condition with many unclarified issues. Circulating autoantibodies targeting the H+/K+-ATPase proton pump of parietal cells are considered markers of AIG, which are used to screen patients with other autoimmune disorders for AIG. However, their diagnostic accuracy in AIG remains unknown.
Active Helicobacter pylori (Hp) infection is detectable in about 25% of AIG patients whose treatment is indicated to reduce inflammation, disease progression and gastric cancer risk. In hypochlorhydric AIG patients bismuth-based eradication regimens without anti-secretory agents may represent an alternative treatment, but, studies on efficacy/ safety of these regimens are lacking.
AIG patients are at increased risk for gastric neoplasms, adenocarcinoma and type 1 carcinoids. In these patients also an increased risk for extra-gastric neoplasms throughout the body has been described, which are poorly investigated.
In AIG, the altered composition of the gastric microbiota due to reduced gastric acid secretion may have a role in gastric carcinogenesis, but data are lacking.
This project is composed of 4 parts to investigate some, not yet clarified issues concerning AIG:
1. To investigate the diagnostic performance of autoantibodies against parietal cells H+, K+-ATPase by an innovative serological assay in a prospective consecutive cohort of naive patients with clinical suspicion of AIG to find out whether these autoantibodies may be considered reliable serological markers of AIG.
2. To investigate the role of bismuth¿based eradication treatment regimens without anti-secretory agents in patients with AIG and active Hp infection by assessing their efficacy and safety.
3. To investigate the risk of extra-gastric neoplasms in patients with AIG and to understand whether surveillance may be needed in this specific clinical setting.
4. To investigate the relationship between the gastric microbiota in patients with AIG and the risk of gastric neoplasms.
The value and feasibility of the research programme are based on the following issues:
1. During the last 25 years, the research group has built a cohort of patients with AG, AIG, and PA whose demographical, clinical, serological and histological data are registered in a database.
2. The research group is composed of gastroenterologists, endoscopists and biochemists with specific clinical and laboratory expertise in the field of gastric pre- and neoplastic lesions as well as autoimmunity, and it is part of national and international research networks on this research topics.
3. The participants form together a solid research group with a specific scientific background in the field of AG, AIG, PA and gastric pre- and neoplastic lesions, whose projects have been granted by University Sapienza in the last 15 years.
The realization of the single parts of this project may contribute to advance of knowledge in the specific topic of AIG as the following results may be expected:
1.To investigate the diagnostic performance of autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase by using an innovative serological assay (luminescent immunoprecipitation system, LIPS) in a prospective consecutive cohort of naive patients with clinical suspicion of AIG in order to find out whether these autoantibodies may be considered reliable serological markers of AIG.
EXPECTED RESULTS: to understand the role of serological autoantibodies against the proton pump of parietal cell as screening tool for AG and/or AIG and its reliability for diagnostic use. A reliable serological marker for the presence of gastric body atrophy, a condition at increased risk for gastric neoplasms, may be useful as it could be easily used in large settings and positive patients should undergo gastroscopy in order to rule out possible neoplasms associated with AG and AIG.
2.To investigate the role of bismuth¿based eradication treatment regimens without any use of anti-secretory agents in patients with AIG and/or PA and active Hp infection by assessing the efficacy and the safety of the treatment, and to assess histological changes of gastric mucosa in cured AIG patients compared to baseline (before eradication).
EXPECTED RESULTS: to find out the utility, efficacy and safety of eradication treatment based on bismuth salts without anti-secretory agents in patients with AIG and to understand whether the eradication of active Hp infection might be able to change or reverse the gastric precancerous lesions. This would be important as specific treatment indications for the subset of patients with AIG are lacking.
3. To investigate the risk of extra-gastric neoplasms in patients with AIG and to understand whether surveillance may be needed in this specific clinical setting.
EXPECTED RESULTS: to quantify the risk of patients with AIG of developing malignancies in other parts of the body and to find out eventual risk factors for developing these extra-gastric malignancies; this would be important as the confirmed risk of extra-gastric malignancies in AIG patients might justify a surveillance of some specific organ or body district, at least in high-risk subgroups.
4. To investigate the relationship between the gastric microbiota in patients with AIG or PA and the risk of gastric neoplasms, i.e. the phenotype of intra-gastric distribution of gastric atrophy and intestinal metaplasia.
EXPECTED RESULTS: to understand the role of the gastric microbiota composition in the risk of developing gastric neoplasms in patients with AIG or PA, eventually opening new perspectives of prevention by treatments able to change the gastric microbiota.