Interleukin- 17agene Polymorphism, Serum Level and Its Tissue Expression in Iraqi Patients Gastric Lesions.

BACKGROUND: T-helper 17 plays a novel role in inflammation in gastritis by producing IL-17A, IL-17A gene polymorphisms that might be responsible for disease susceptibility and development of different gastric lesions. OBJECTIVE: The aims of study was to determine the association of IL-17A (G197A) genotype and allele frequency with disease phenotype and risk with different gastric lesions. METHODS: Case controlled study involved 30 gastroduodenal ulcer, 30 chronic gastritis and 30 subjects as a control group with negative endoscopic findings. After genomic DNA extraction, IL-17A (G197A)ARMS-PCR genotyping were done for all cases. Serum IL-17A was measured using ELISA method and tissue expression was visualized using immunohistochemistry staining method. RESULTS: The results showed that allele A was significantly frequent in gastroduodenal ulcer more than that in healthy control odd ratio= 4 (1.42-10.46), and none significantly with chronic gastritis p=0.071. Serum IL-17A was significantly higher in gastroduodenal ulcer (116.45±48.09 pg/ml), chronic gastritis (78.02±30.17pg/ml) and healthy control 19.36±9.28 pg/ml).However, the serum IL-17A level is not related to the allele pattern of each group. The tissue expression was expressed as dense granular cytoplasmic and membranous of inflammatory cells. Interestingly, the percentage of IL-17A protein expression was significantly higher in gastroduodenal ulcer (38.2±16.55%), chronic gastritis (30.89±14.02%) and normal mucosa (2.8±3.02%). Furthermore, patients with strong intensity of IL-17A stained mucosa were frequently carrier for mutant allele (68%). CONCLUSION: IL-17A might predispose for aggressive inflammation of advanced lesions in stomach like ulcer.

Development of an in-house capture ELISA: An attempt to detect CagA antigen in sera of Helicobacter pylori infected patients.

The CagA protein one of the key virulence factors of Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer diseases. Unfortunately the cagA gene status can only be determined by PCR while serology is an alternative approach to detect antigens or antibodies. Our aim is to detect the CagA antigen in sera of infected subjects by the development of an in-house capture ELISA test. Gastric antral biopsies and serum samples were collected from 63 patients. PCR was used to determine the cagA status. Our previously developed recombinant CagA protein and monoclonal antibody were used for setting up the capture ELISA test. H. pylori positive [(38 gastritis, 14 duodenal ulcers (DU), 11 gastric ulcer (GU)] patients were determined by PCR. The cagA gene was detected in 21 (55%) of gastritis, 11 (78%) of DU and 7 (60%) of GU patients. The reagents used in setting up the capture ELISA test following optimization displayed high performance. This study showed that our developed in-house capture ELISA has the potential to detect the CagA antigen at very low concentrations even though not detected in our H. pylori infected patients sera but we are also intended to use it in saliva and stool samples.

Pediatric gastritis and its impact on hematologic parameters.

Non-invasive biomarkers, such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, may predict inflammation in various disorders, including gastritis, according to recent data. Nevertheless, various studies reported an association between Helicobacter pylori (H pylori) and immune thrombocytopenia in both adults and pediatric patients. The objective of our study was to evaluate the impact of pediatric gastritis, caused or not by H pylori infection on erythrocytes, their parameters, thrombocytes, mean platelet volume, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).We performed a prospective, case-control study on 151 patients aged between 1 and 17 years who presented with chronic dyspeptic symptoms. An upper digestive endoscopy with gastric biopsies and a complete blood count was performed in each case.Control group consisted of 67 patients with normal histological findings, while the two study groups were divided into group 1-H pylori-induced gastritis (31 patients) and group 2-non-H pylori-induced gastritis (53 patients). Children from the rural area were more likely to develop both types of gastritis (P < .01). No significant difference was found between either of the study groups and control group in terms of platelets, mean platelet volume, NLR and PLR (P > .05). However, significantly higher values of lymphocytes were associated with non-H pylori-induced gastritis (P < .01). Comparison of the two study groups did not reflect any significant differences in terms of hematological parameters. When assessing these constants in relation to gastritis severity, severe gastritis led to a compelling decrease in hemoglobin (Hb) and hematocrit (Htc) levels. The comparison of parameters between severe, moderate, and mild gastritis did not reveal any significant results.Childhood and adolescent gastritis does not produce a significant effect upon platelet counts, their mean volume, PLR or NLR, according to our study. An important increase in lymphocyte count might predict non-H pylori pediatric gastritis. Moreover, severe gastritis might result in an important decrease in Hb and Htc levels.

Collagenous Gastritis in Children: Incidence, Disease Course, and Associations With Autoimmunity and Inflammatory Markers.

INTRODUCTION: Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients. METHODS: Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally. RESULTS: The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient. DISCUSSION: The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).

Comparison of different immunoassays for the detection of antibodies against Intrinsic Factor and Parietal Cells.

OBJECTIVES: In the diagnostic work up of autoimmune gastritis several immunological methods are available for the detection of antibodies against Intrinsic Factor (IF) and Parietal Cells (PC). However, there are no recent reports directly comparing all the available assays and methods. The objective of this study was to compare the performance of several commercially available anti-IF and anti-PC antibody assays from different manufacturers in a multi-center multi-cohort setting. METHODS: Sera were used from 5 different cohorts consisting of samples from 25 healthy elderly, 20 HCV or HIV positive patients and 150 patients positive for anti-IF or anti-PC antibodies or in whom these antibodies were requested. These cohorts were tested for anti-IF antibodies with 6 different assays (IIF, ELISA, DIA and EliA) and for anti-PC antibodies with 7 different assays (IIF, ELISA, DIA and EliA). Performance was evaluated by calculating the concordance and relative sensitivity and specificity. RESULTS: Good concordance was found between the assays for both antibody specificities, ranging from 81 to 100% and 91-100% for anti-IF and anti-PC antibodies, respectively. Highest relative sensitivity was found with the (automated) ELISA based methods. However, all assays had a relative sensitivity between 85 and 100% for anti-IF antibodies and between 95 and 100% for anti-PC antibodies. The relative specificity ranged between 76 and 100% for anti-IF antibodies and between 96 and 100% for anti-PC antibodies. CONCLUSIONS: We conclude that most assays perform well and are concordant to each other, despite the methodological differences and the different sources of antigen used. However, the method used affects the sensitivity and specificity. The (automated) ELISA based assays have the highest relative sensitivity and relative specificity. Care should be taken in the interpretation of positive results by IIF and negative results by the Blue Diver when testing for anti-IF antibodies.

Associations of Helicobacter pylori seropositivity and gastric inflammation with pediatric asthma.

OBJECTIVE: Controversy exists regarding an association between Helicobacter pylori infection and asthma in children. We examined the hypotheses of inverse associations of H. pylori seroprevalence and pepsinogen (PG) levels, as markers of gastric inflammation, with asthma in children. METHODS: A hospital-based case-control study was conducted among children aged 4.8 to 17.3 years in Israel. Confirmed asthma cases (n = 75) were recruited through a pulmonary clinic, and controls (n = 160) without asthma were enrolled. Using enzyme-linked immunosorbent assays we measured the presence of H. pylori immunoglobulin G (IgG) antibodies, IgG antibodies to cytotoxin-associated gene A antigen (CagA) (virulent factor), serum PG levels and exposure to other enteric pathogens (Shigella flexneri). Multivariable logistic regression models were applied. RESULTS: H. pylori IgG seropositivity was 25% and 40% among cases and controls, respectively (P = .03). H. pylori CagA IgG seropositivity was associated with reduced risk of asthma (adjusted odds ratio [OR], 0.33 [95% CI, 0.11-0.95] but not for the CagA negative serology (adjusted OR, 0.70 [95% CI, 0.32-1.54]). Children who were H. pylori seropositive with a PGI:PGII of ≤6.78 (severe gastric inflammation) had a lower likelihood of asthma (adjusted OR, 0.31 [95% CI, 0.10-0.89]) than did seronegative children. Exposure to Shigella flexneri did not differ between cases and controls, nor according to H. pylori seropositivity. Among the asthmatic children, pulmonary function did not differ according to H. pylori seropositivity. CONCLUSIONS: H. pylori infection and its related gastric inflammation may have a protective role in the risk of pediatric asthma and further research into a potential causal pathway is required.

Serology Is More Sensitive Than Urea Breath Test or Stool Antigen for the Initial Diagnosis of Helicobacter pylori Gastritis When Compared With Histopathology.

OBJECTIVES: To assess the concordance and performance characteristics of Helicobacter pylori laboratory tests compared with histopathology and to propose algorithms for the diagnosis of H pylori that minimize diagnostic error. METHODS: H pylori diagnostics were reviewed from a 12-year period within a health system (2,560 cases). Analyses were performed to adjust diagnostic performance based on treatment and consensus histopathologic diagnoses among pathologists. Markers of access to care, including test cancellation frequency and turnaround time, were assessed. Costs and performance of candidate noninvasive testing algorithms were modeled as a function of disease prevalence. RESULTS: Serum H pylori IgG demonstrated a higher sensitivity (0.94) than urea breath and stool antigen tests (0.64 and 0.61, respectively). Evidence of an advantage in access to care for serology included a lower cancellation rate. Interobserver variability was higher (κ = 0.34) among pathologists for cases with a discordant laboratory test than concordant cases (κ = 0.56). A model testing algorithm utilizing serology for first-time diagnoses minimizes diagnostic error. CONCLUSIONS: Although H pylori serology has modestly lower specificity than other noninvasive tests, the superior sensitivity and negative predictive value in our population support its use as a noninvasive test to rule out H pylori infection. Reflexive testing with positive serology followed by either stool antigen or urea breath test may optimize diagnostic accuracy in low-prevalence populations.

Enhanced Frequency of CD19+IL-10+B Cells in Human Gastric Mucosa Infected by Helicobacter pylori.

BACKGROUND: CD19+IL-10+B cells are considered as a particular subset of immunosuppressive cells by producing interleukin 10 (IL-10), which plays an important role in infectious and autoimmune diseases. The aim of this study was to determine the number of CD19+IL-10+B cells in Helicobacter pylori (H. pylori) positive patients in comparison with H. pylori negative patients, and to determine the association with different clinical outcomes, such as gastritis and peptic ulcer disease (PUD), in infected patients. METHODS AND MATERIALS: We studied 25 infected patients with gastritis, 25 infected patients with PUD, and 25 patients negative for H. pylori. The number of CD19+IL-10+B cells was determined by immunofluorescence. RESULTS: The number of CD19+IL-10+B cells in patients infected with H. pylori was significantly 2.5-fold higher than uninfected patients (P < 0.0001). Also, the number of CD19+IL-10+B cells in infected patients with gastritis was significantly 1.45-fold elevated compared to infected patients with PUD (P = 0.001). CONCLUSIONS: These results demonstrate that the increased number of CD19+IL-10+B cells in infected patients and its association with other cells may play an important role in the pathogenesis of H. pylori infection.

Chromogranin Serves as Novel Biomarker of Endocrine and Gastric Autoimmunity.

CONTEXT: The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. OBJECTIVE: To investigate CgA utility as a marker of endocrine autoimmunity. METHODS: CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology. RESULTS: Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P < 0.0001) and 3.89 (P = 0.0073) in patients with NET, T1D, AG, and AP, respectively. In AG, CgA and serum gastrin correlated positively (r = 0.55; P < 0.0001). The area under the receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 vs 0.67; P < 0.0001). However, in combination with PCA and intrinsic factor autoantibodies, CgA independently improved prediction of AG (OR 6.5; P = 0.031). An impact of age on CgA positivity and on CgA value was detected (P < 0.0001) while current smoking significantly increased CgA serum levels by 25% (P = 0.0080). CONCLUSION: CgA qualifies as a novel biomarker for T1D, AP, and AG.

Serum pepsinogens as a gastric cancer and gastritis biomarker in South and Southeast Asian populations.

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker.

LncRNAs adjacent to pepsinogen C in gastric diseases and diagnostic efficiencies of joint detection in gastric diseases.

Aims: We aimed to explore diagnostic efficiencies of long noncoding RNAs (lncRNAs) adjacent to PGC combining with sPGC and anti-Helicobacter pylori IgG in identifying GC (gastric cancer) and precancerous disease. Patients & methods: A total of 265 patients with different gastric diseases were collected. ELISA was to detect sPGC and anti-H. pylori IgG. LncRNAs was determined by qRT-PCR. Results: The area under receiver operating characteristic curve of lncRNAs in discriminating GC+AG (atrophic gastritis) and superficial gastritis (SG) were 79.0, 68.1 and 75.9%. The diagnostic performance of lncRNAs with sPGC had increasing trends in distinguishing GC from non-GC, SG from GC+AG comparing with lncRNAs, with no statistic difference. Diagnosis efficacies of lncRNAs with anti-H. pylori IgG improved dramatically. Conclusions: Serum lncRNAs could distinguish GC, AG and SG. Diagnosis efficiencies of lncRNAs with sPGC and anti-H. pylori-IgG could be improved.

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research.

OBJECTIVES: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. METHODS: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. RESULTS: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p = 0.001). CONCLUSIONS: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

Eosinophil counts in colonic tissue eosinophilia: Investigating specificity and sensitivity of cutoff points and comparing two counting methods.

BACKGROUND/AIMS: The aim of this study was to investigate the specificity and sensitivity of eosinophil cutoff points defining the colonic tissue eosinophilia (TE) and compare the yield of reporting the highest count versus the mean of five high-power fields (HPFs). MATERIALS AND METHODS: One hundred and seventy-one cases of colonic TE, including 22 primary eosinophilic colitis (PEC) cases, were compared to one hundred and twenty-one normal controls in the University of Jordan. The highest eosinophil count (EC) and the mean of five HPFs were recorded. The receiver operating characteristic curve (ROC) analysis was used to find the cutoff point with the best sensitivity and specificity. RESULTS: There was no significant advantage of counting five fields over counting the most densely populated HPF. Using 30 eosinophils per HPF achieved 80% sensitivity and 65% specificity. This point is close to the mean in normal controls plus one standard deviation (SD) (29 per HPF). However, there was overlap between normal counts and TE, using 30 as a cutoff point resulted in 35% false-positive rate. There was no reliable cutoff point to differentiate PEC from secondary TE. CONCLUSION: We recommend reporting the highest EC in colonic biopsies and using 30 as a cutoff point, bearing in mind the overlap with normal and correlating with the clinical team to not treat asymptomatic patients. Clinicopathological correlation is essential to separate PEC from secondary TE.

Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease.

OBJECTIVE: Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening. METHODS: We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam. RESULTS: PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed. CONCLUSION: In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.

Accuracies of Endoscopic Diagnosis of Helicobacter pylori-Gastritis: Multicenter Prospective Study Using White Light Imaging and Linked Color Imaging.

INTRODUCTION: The diagnosis of Helicobacter pylori infection status with white light imaging (WLI) is difficult. We evaluated the accuracies of using WLI and linked color imaging (LCI) for diagnosing H. pylori-active gastritis in a multicenter prospective study setting. METHODS: Patients who underwent esophagogastroduodenoscopy were prospectively included. The image collection process was randomized and anonymous, and the image set included 4 images with WLI or 4 images with LCI in the corpus that 5 reviewers separately evaluated. Active gastritis was defined as positive when there was diffuse redness in WLI and crimson coloring in LCI. The H. pylori infection status was determined by the urea breath test and the serum antibody test. Cases in which both test results were negative but atrophy or intestinal metaplasia was histologically confirmed were defined as past infections. The primary endpoint was the diagnostic accuracies of WLI and LCI, and the secondary endpoint was inter-observer agreement. RESULTS: Data for 127 patients were analyzed. The endoscopic diagnostic accuracy for active gastritis was 79.5 (sensitivity of 84.4 and specificity of 74.6) with WLI and 86.6 (sensitivity of 84.4 and specificity of 88.9) with LCI (p = 0.029). LCI significantly improved the accuracy in patients with past infections over WLI (36.8 in WLI and 78.9 in LCI, p < 0.01). The κ values were 0.59 in WLI and 0.70 in LCI. CONCLUSIONS: LCI is useful for endoscopic diagnosis of H. pylori-active or inactive gastritis, and it is advantageous for patients with past infections of inactive gastritis.

Thiol/disulfide homeostasis and ischemia modified albumin levels in autoimmune gastritis and their relations with gastric emptying

Background/aim: Autoimmune gastritis is an autoimmune and inflammatory disorder. The aim of this study is to examine dynamic thiol/disulfide homeostasis and ischemia modified albumin levels, and to analyze the association between thiol/disulfide homeostasis and gastric emptying time in autoimmune gastritis. Materials and methods: Thiol/disulfide homeostasis tests and ischemia modified albumin levels were determined in 50 autoimmune gastritis patients and 53 healthy subjects. Patients with delayed and normal gastric emptying were compared by thiol/disulfide homeostasis tests. Results: The results showed that native thiol (µmol/L), total thiol (µmol/L), and native thiol/total thiol ratio (%) of the patients with autoimmune gastritis decreased compared to the control group (177.7 ± 34.18 vs. 245.25 ± 33.83, P = 0.001, 227.25 ± 36.78 vs. 284.20 ± 27.19, P = 0.03, and 8.84 ± 1.1 vs. 7.74% ± 1.3%, P = 0.001). In addition, native thiol (µmol/L), total thiol (µmol/L), and native thiol/ total thiol ratio (%) were found to be lower in patients with delayed gastric emptying (198.65 ± 24.27 vs. 167.12 ± 20.51, 241.81 ± 27.14 vs. 213.92 ± 26.35, 8.34 ± 1.29 vs. 7.20 ± 1.83, P = 0.001). Disulfide level, disulfide/native thiol, disulfide/total thiol (P = 0.001) ratios, and ischemia modified albumin levels (ABSU, 0.71 ± 0.08 vs. 0.83 ± 0.07) were found to be higher in autoimmune gastritis patients with delayed gastric emptying (P = 0.001). Conclusion: The results showed that thiol/disulfide homeostasis in patients with autoimmune gastritis caused an increase in ischemia modified albumin and disulfide whereas a decrease in thiols. An altered thiol/disulfide balance was also observed in patients with delayed gastric emptying. These results suggest that the oxidative process is involved in patients with autoimmune gastritis.

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.

BACKGROUND: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. OBJECTIVE: We aimed to develop tissue- and blood-based diagnostic platforms for EG. METHODS: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. RESULTS: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). CONCLUSION: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.