Autoimmune atrophic gastritis in systemic sclerosis

Systemic sclerosis (SSc) is a rare connective tissue disorder with a complex pathogenesis involving vascular dysfunction, small vessel proliferation as well as alterations of innate and adaptive immunity. Gastrointestinal (GI) involvement in SSc is almost universal and affects nearly 90% of the patients. Of all the GI manifestations, 30%–75% are oesophageal abnormalities, including gastro-oesophageal reflux disease, reflux oesophagitis and Barret’s oesophagus. The incidence of gastric manifestations is about 22% with a common presentation of gastric antral vascular ectasia (GAVE). However, autoimmune atrophic gastritis (AIG) is not a known manifestation of SSc. Our case has a unique presentation of the coexistence of GAVE and AIG. We have conducted a thorough literature review to study a possible association of AIG and SSc and understand the pathology of SSc.

Serum TSH Levels Normalisation in Patients Affected by Autoimmune Atrophic Gastritis, After the Switch From Oral L-T4 in Tablet Form to L-T4 in Liquid Formulation

Patients affected by autoimmune atrophic gastritis could have some issues in L-thyroxine (L-T4) absorption, due to drug malabsorption, induced by the increased gastric pH. Different factors influence L-T4 absorption, such as dietary habits, interference with other drugs, absorption kinetics, age of the patient, adherence to therapy, and others. We enrolled 36 patients affected by autoimmune atrophic gastritis with high serum thyrotropin (TSH) levels under therapy with L-T4 in the tablet formulation. L-T4 tablets were changed to an oral liquid L-T4 preparation, maintaining the same dose. The switch from L-T4 in tablet formulation to the liquid one, at the same L-T4 dosage, led to the normalisation/reduction of circulating TSH levels. Then 14 patients, who were switched back again to receive L-T4 in tablets (with the same dose), had a worsening of TSH values, falling in the hypothyroid range. In conclusion, our findings led to hypothesize that the pH alteration issue caused by autoimmune atrophic gastritis could be overcome by the oral L-T4 liquid formulation administration.

The Level of Serum Pepsinogen in Diagnosing and Evaluating the Severity of Subacute Combined Degeneration Due to Vitamin B12 Deficiency

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio <3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P < 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P < 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.

Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer

Background Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC. Methods Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC–MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients. Results 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC–MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was “tricarboxylic acid cycle”. Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC). Conclusion This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.

Serum pepsinogen levels and OLGA/OLGIM staging in the assessment of atrophic gastritis types

BackgroundWe assessed the validity of using serum pepsinogen tests (sPGTs) to differentiate autoimmune atrophic gastritis (AAG) from environmental atrophic gastritis (EAG). We also investigated the correlation and prognostic value between disease stage, according to Operative Link for Gastritis Assessment (OLGA)/Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM), and sPGT results in patients with gastric atrophy.MethodsWe enroled 115 patients in this prospective study: 95 with atrophic gastritis (16 with AAG and 79 with EAG) and 20 non-atrophic gastritis. These patients, along with 32 control patients, underwent esophagogastroduodenoscopy. Atrophy and intestinal metaplasia of the gastric biopsy specimens were staged according to the OLGA/OLGIM staging systems.ResultsThe median (IQR) age of the patients (83 females (56.5%)) was 58 (46–67) years. Patients in the AAG group represented histologically advanced stages. The AAG group had lower pepsinogen (PG) I and II levels, as well as a lower PGI/PGII ratio, compared with the EAG group (p<0.01, p<0.05 and p<0.01, respectively). The optimal PGI/PGII ratio for predicting AAG was ≤1.9 (100% sensitivity and 100% specificity), and that for predicting EAG was ≤9.2 (47.5% sensitivity and 90.6% specificity). The OLGA/OLGIM stage was negatively correlated with the PGI level and PGI/PGII ratio. In the AAG group, four of five patients with low-grade dysplasia had OLGA/OLGIM stage III–IV disease.ConclusionssPGT may provide valuable information for differentiating advanced-stage AAG from EAG, and in patients with atrophic gastritis, use of sPGTs and OLGA/OLGIM staging together may predict gastric cancer risk.