Autoimmune gastritis (AIG) is characterized by an immunologically-driven destruction of gastric glands with atrophy of the oxyntic mucosa with reduced gastric acid secretion. Late stage AIG is often associated with pernicious anaemia (PA). AIG, in particular when associated with intestinal metaplasia (IM), is considered a risk factor for gastric cancer, according to the described multistep progression. Corpus-restricted AIG and PA is not considered part of the precancerous cascade. A systematic review showed in AIG patients with PA a pooled GC incidence-rate of 0.3% person-year and an estimated 7-fold RR of GC. In AIG, gastric cancer risk may be increased due to intra-gastric changes as increased pH and oxidative stress as a consequence of Hp leading to overgrowth of other bacteria than Hp. The altered composition of gastric microbiota may have a role in gastric carcinogenesis, but data are conflicting. Pathological evaluation of gastric biopsies is the gold-standard for AIG diagnosis, non-invasive serological tests include fasting gastrinaemia, pepsinogen I levels and parietal cells autoantibodies (PCA) and complete blood count and serum cobalamin levels. PCA are often used to screen patients with other autoimmune disorders for AIG albeit data on their reliability are lacking. Autoantibodies against ATP4A and ATP4B antigens have been reported to be virtually always present in patients which known diagnosis of AIG by an innovative luminescent immunoprecipation system. Reliable serological markers for the presence of AIG, a condition at increased risk for gastric neoplasias, may be useful as it could be easily used in large settings and positive patients should undergo gastroscopy in order to optimize the use of endoscopic resources to rule out possible neoplasms associated with AIG.
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 AIG and PA recording clinical data and collecting serological and histological specimens.
2. The research group is composed of gastroenterologists and endoscopists with specific clinical and laboratory expertise in the field of gastric pre- and neoplastic lesions as well as autoimmunity, and this group participates in national and international research programmes on these topics.
3. The participants form together a solid research group with a specific scientific background in the field of AIG, PA, and gastric pre- and neoplastic lesions, whose projects have been granted by the Sapienza University in the last 15 years.
The realization of the single parts of this research programme may contribute to advance of knowledge in the specific field of AIG and PA as the following results may be expected:
1. To investigate in patients with AIG the possible link between the gastric microbiota composition and the risk of gastric neoplasia in order to provide new insights into the increased neoplastic risk of these patients and to possibly open the way for new developable strategies to prevent this long-term malignant complication.
EXPECTED RESULTS: to understand the role of the gastric microbiota composition in the risk of developing gastric neoplasias in patients with AIG or PA, eventually opening new perspectives of prevention by treatments able to change the gastric microbiota.
2. To investigate the occurrence of gastric autoantibodies against parietal cells and against intrinsic factor by a novel serological assay in patients with high clinical suspicion of AIG to assess their reliability as serological markers of AIG for a potential application in a case-finding strategy in possible high-risk group.
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 neoplasias, may be useful as it could be easily used in large settings and positive patients should undergo gastroscopy in order to rule out possible neoplasias associated with AG and AIG.
3. To investigate in a cohort of AIG patients stratified according to risk groups (as presence of pernicious or iron-deficiency anemia, family history of gastric cancer) the occurrence of gastric malignant complications when monitored by gastroscopy/histology at 3 year-intervals according to European guidelines (MAPS), and to assess in the same cohort the associated risk of extra-gastric malignant complications
EXPECTED RESULTS: to quantity the risk of patients with AIG of developing gastric neoplasias and 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.