Nome e qualifica del proponente del progetto: 
sb_p_1996284
Anno: 
2020
Abstract: 

Autoimmune atrophic gastritis(AAG) is characterized by reduced gastric acid secretion and increased gastric cancer(GC) risk. Parietal cell(PCA) and intrinsic factor autoantibodies(IFA) are considered markers for AAG; the role of pepsinogens, gastrin, and Helicobacter pylori(Hp) antibodies in the noninvasive AAG assessment is not established. The diagnostic performance of Narrowband imaging(NBI) and blue light imaging(BLI) electronic chromoendoscopy(EC) for gastric metaplasia may be improvable by artificial intelligence(AI) algorithms. Hp infection may be found in AAG, challenging differential diagnosis with Hp-AG. Distinctive inflammatory-metaplastic patterns between AAG and Hp-AG are not clear. Gastric dysbiosis may have a role in the multifactorial gastric carcinogenesis. AAG might be a model to investigate hypochlorhydria consequences on colonic microbiota composition.
This project is composed of 5 parts:
1. To investigate AAG prevalence and usefulness/feasibility of a proactive case-finding strategy for AAG by assessing in healthy blood donors serological markers of AAG (PCA) and gastric atrophy (pepsinogen I) and Hp.
2. To investigate in AAG patients the role of autoantibodies towards IFA by LIPS.
3. To investigate in AAG patients the applicability of AI-assisted-EC as a computer-aided diagnostic system to assess gastric metaplasia (intestinal and pseudopyloric) compared to biopsy-based histopathological markers.
4. To investigate in AAG patients the role of Hp infection by assessing seroreactivity against Hp-specific antigens and the immunophenotype of the gastric mucosal inflammatory response and metaplastic changes.
5. To investigate in AAG patients the role of gastric-colonic microbiota composition as possible cofactors associated with different clinical outcomes like micronutrient deficiencies, gastrointestinal symptoms, and gastric neoplastic complications.

ERC: 
LS4_8
LS6_2
LS6_3
Componenti gruppo di ricerca: 
sb_cp_is_2518341
sb_cp_is_2519433
sb_cp_is_2520171
sb_cp_is_2520562
sb_cp_is_2520425
sb_cp_es_361166
sb_cp_es_361167
sb_cp_es_361168
sb_cp_es_361169
sb_cp_es_361170
sb_cp_es_361165
Innovatività: 

The research group is composed of gastroenterologists, endoscopists, pathologists, and biochemists with specific clinical and laboratory expertise in the field of gastric pre- and neoplastic lesions and autoimmunity, and it is part of national and international research networks on this research topics. The participants form a robust research group with a valid scientific background in the field of AAG, PA, and gastric pre- and neoplastic lesions, whose projects have been granted by Sapienza University in the last 15 years. During the last 25 years, the patient-facing clinical activity combined with the research activity has led to a substantial cultural growth of the research staff, and our gastroenterology outpatient clinic has grown up to a known referral center for anemia and malabsorption of micronutrients, gastric autoimmunity, and gastric preneoplastic conditions.
The realization of this project may contribute to the advance of knowledge in specific topics of AAG:
1. To investigate the prevalence of AAG and the usefulness and feasibility of a proactive case-finding strategy for AAG by assessing in healthy blood donors the presence of serological markers of AAG (antibodies towards parietals cells) and gastric atrophy (pepsinogen I) as well as Hp infection.
EXPECTED RESULTS: To assess the prevalence of AAG in apparently healthy subjects and the feasibility of a pro-active non-invasive case-finding strategy for AAG by using an innovative panel of serological markers for AAG providing insights into the occurrence of misdiagnosed patients with AAG in the general population, and the need of a serological pre-endoscopic screening for this condition at GC risk.
2. To investigate in patients with AAG the role of IFA, a classical serological marker of PA, by LIPS, an innovative liquid phase immunoassay, reported as an ideal platform for autoantibodies assessment in a wide range of autoimmune diseases including atrophic gastritis.
EXPECTED RESULTS: To understand the role of IFA as a serological biomarker for AAG and its reliability for diagnostic use of manifest or latent PA. Cobalamin deficiency, potentially leading to hematological and neurological complications, may not be present at AAG diagnosis, but develop during the disease course. A reliable serological marker for latent or manifest PA in AAG may be useful to complete AAG assessment at diagnosis and follow-up.
3. To investigate in patients with AAG the applicability of AI-assisted electronic chromoendoscopy as a computer-aided diagnostic system to assess gastric metaplasia compared to biopsy-based histopathological markers to provide an innovative diagnostic approach and prognostic tool to AAG patients in terms of clinical outcome and gastric neoplastic risk.
The obtained results should be the basis for the development of specific software for an AI-assisted diagnosis of gastric preneoplastic lesions during gastroscopy in white-light or HR-NBI/BLE-EC. AI-assisted endoscopic diagnosis is expected to improve the detection rate of gastric preneoplastic lesions, thus reducing misdiagnosis, and improving the efficiency/quality of gastroscopy by waiving or targeting biopsies to areas with a high positive predictive value of preneoplastic changes.
4. To investigate in AAG patients the role of Hp infection by assessing the seroreactivity against Hp-specific antigens and the immunophenotype of the gastric mucosal inflammatory response and metaplastic changes to provide insights into a possible (causal or casual) association of this bacterium with AAG.
EXPECTED RESULTS: The role of Hp in AAG is not yet clarified, as AAG may occur as a long-term consequence of chronic Hp infection and active Hp infection may be associated with AAG as ¿innocent bystander¿. This section of the project should help to understand whether the presence or the previous exposure to Hp may lead to changes of the immunophenotype of gastric inflammation and metaplastic adaption at a histopathological level potentially useful in establishing a role of Hp in AAG, and eventually explaining different clinical outcomes as neoplastic complications of AAG patients not linked to high-risk OLGA/OLGIM stages.
5. To investigate in patients with AAG the role of the gastric and colonic microbiota composition as possible cofactor associated to different clinical outcomes to provide new insights into the complex multifaceted clinical pictures related to this disorder and to possibly pave the way for innovative potential treatment strategies
EXPECTED RESULTS: Insights in this field may shed light on the role of hypochlorhydria in gastric and colonic dysbiosis and clinical consequences of AAG and may open new perspectives for potential prevention measures of neoplastic and other clinical complications of AAG as the modulation of the gastrointestinal microbiota.

Codice Bando: 
1996284

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