gastrin-17 and Autoimmune-Diseases

Autoimmune diseases, characterized by an alteration of the immune system which results in a loss of tolerance to self antigens often coexist in the same patient. Autoimmune atrophic gastritis, characterized by the development of antibodies agains parietal cells and against intrinsic factor, leads to mucosal destruction that affects primarily the corpus and fundus of the stomach. Autoimmune atrophic gastritis is frequently found in association with thyroid disease, including Hashimoto's thyroiditis, and with type 1 diabetes mellitus, Other autoimmune conditions that have been described in association with autoimmune atrophic gastritis are Addison's disease, chronic spontaneous urticaria, myasthenia gravis, vitiligo, and perioral cutaneous autoimmune conditions, especially erosive oral lichen planus. Interestingly, however, celiac disease, another frequent autoimmune condition, seems to play a protective role for autoimmune atrophic gastritis. The elevated prevalence of autoimmune disease clustering should prompt the clinicial to exclude concomitant autoimmune conditions upon diagnosis of any autoimmune disease.

Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Biomarkers; Comorbidity; Disease Susceptibility; Gastrins; Gastritis, Atrophic; Humans; Intrinsic Factor; Parietal Cells, Gastric; Pepsinogens; Prevalence; Sensitivity and Specificity

Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG.. Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared.. Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit.. Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

Topics: Aged; Antibodies, Bacterial; Autoimmune Diseases; Biomarkers; Endoscopy, Digestive System; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter pylori; Humans; Italy; Male; Middle Aged; Pepsinogens; Prospective Studies; Proton Pump Inhibitors

Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis.. We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017.. A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET.. This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Biomarkers; Diagnosis, Differential; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pepsinogen A; Pepsinogen C; Prevalence; Retrospective Studies; ROC Curve; Stomach Neoplasms; Young Adult

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterised by destruction of gastric oxyntic mucosa AIM: To explore gastric histopathological evolution in a cohort of AAG patients over a prolonged follow-up METHODS: Single centre prospective study enrolling consecutive patients with histologically confirmed AAG between 2000 and 2018. All AAG patients undergoing endoscopic follow-up every 1-3 years were classified as having stages 1, 2 or 3 according to atrophy severity (mild, moderate and severe). AAG patients with either glandular or neuroendocrine dysplasia/neoplasia were classified as having stage 4. Disease stage progression, and changes in serum anti-parietal cell antibody (PCA), chromogranin A and gastrin-17 were assessed.. In total, 282 AAG patients (mean age 60.3 years; F:M ratio 2.4:1; median follow-up 3 years, interquartile range 1-7) were enrolled. All patients with stages 1 or 2 progressed to stage 2 or 3 over time with a steady trend (P = .243) and regression from a severe to a milder stage was never noticed. Disease progression of patients with stages 1 or 2 occurred within the first 3 years. PCA positivity rate did not change over time. Stage 3 patients had higher gastrin-17 levels compared to patients with stages 1 and 2 (median 606 vs 295 pg/mL; P < .001). In stage 3, the hazard ratio for the risk of developing stage 4 was 6.6 (95% CI 1.5-29; P = .001).. AAG is a steadily progressive disease, in which stages 1 and 2 always progress to stage 3. The risk of developing a complicated disease stage is greater in patients with more severe gastric lesions.

Topics: Adult; Aged; Autoimmune Diseases; Disease Progression; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Neuroendocrine Tumors; Prospective Studies; Severity of Illness Index; Stomach Neoplasms

To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection.. Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology.. Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively).. H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrophy; Autoimmune Diseases; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Humans; Male; Middle Aged; Pepsinogen A; Prospective Studies; Young Adult