J Clin Med. 2023 Sep 23;12(19):6152. doi: 10.3390/jcm12196152.
* Strongest known risk factor for GC development is infection with the bacterium Helicobacter pylori (H. pylori)
* Endoscopic surveillance of gastric precancerous lesions (GPL) such as atrophic gastritis (AG) or intestinal metaplasia (IM) decreases the risk of developing invasive GC.
* Another cause of chronic gastritis is autoimmune gastritis (AIG), an immune-mediated disorder characterized with the destruction of gastric parietal cells.
* We investigated the prevalence of AIG in a prospectively followed cohort of patients with GPL.
* Clinical characteristics of AIG-associated IM and attempted to determine the diagnostic efficiency of gastric function biomarkers to optimize the detection of AIG in patients with GPL.
<Study populations>
* Prospective, multicenter study
* AIG-associated pathological features were re-evaluated in APCA-positive patients to confirm the diagnosis of AIG.
<Results>
1. Prevalence of AIG Is Increased in Patients with Gastric Premalignant Lesions
* APCA positivity was seen for 51 individuals, 36 of whom were women.
* A significantly higher prevalence of APCA positivity was seen in the GPL group as compared to the control cohort (18% vs. 7%, p = 0.033).
* The multivariable logistic regression analysis showed that APCA positivity (adjusted OR = 3.76, 95% CI = −1.31 to 10.79; p = 0.013), age (adjusted OR = 1.07, 95% CI = −1.04 to 1.09; p < 0.001) and male gender (adjusted OR = 0.47, 95% CI = −0.26 to 0.86; p = 0.015) were independently associated with IM.
Table 1. Baseline characteristics of study population and association between age, gender, APCA positivity, H. pylori infection history and GPL.
* Only three of the APCA-positive GPL cases were previously identified with AIG. (AIG may go underdiagnosed in patients with GPL)
* More than half of patients presented with low vitamin B12 levels (54.3%).
* Concomitant autoimmune disease was observed in 23.7% of cases (ATD: 19.5%).
* 19 presented with limited AG/IM lesions (44.2%, under surveillance according to the MAPSII guidelines )
2. AIG in GPL Patients Is Associated with Gastric Location, but Not Severity of GPL
* 51.2% (24/43) of APCA-positive patients have extended GPL, which is significantly more than in APCA-negative patients.
* Corpus involvement was more frequently identified in APCA-positive patients
* Antrum involvement was more frequently identified in APCA-negative subjects
Table 2. Distribution of precancerous lesion in the gastric mucosa of patients with or without anti-parietal-cell antibodies.
* OLGIM score was not affected by either APCA status (p = 0.16) or concentration of APCA (r = −0.06; p = 0.62; Figure 1A, C).
* OLGA score was lower in patients without APCA (p < 0.001).
* APCA levels did not correlate to severity of atrophy (r = 0.14; p = 0.31; Figure 1B,D).
Figure 1. Association between anti-parietal cell antibodies and severity of intestinal metaplasia and gastric atrophy. (A) No differences in Operative Link for Gastric Intestinal Metaplasia Assessment (OLGIM) stage were seen for cases with GPL positivity for anti-parietal cell antibodies (APCA) and those negative for APCA (p = 0.16). (B) Operative Link of Gastritis Assessment (OLGA) score of zero was more often seen for GPL cases without APCA (p < 0.001). (C) Serum concentration of APCA did not correlate with OLGIM score (r = −0.06; p = 0.62). (D) Serum concentration of APCA did not correlate with OLGA score (r = 0.14; p = 0.31).
* APCA was also compared to the worst OLGIM and OLGA score seen at any time during follow up, with similar results
Supplementary Figure S1. Serum concentration of APCA did not correlate with the worst OLGIM score detected during longitudinal follow-up (A, r=-0.1; p=0.39) or the worst OLGA stage (B, r=0.01; p=0.96).
3. AIG in the Context of Precancerous Gastric Lesions Is Associated with Serum Markers Indicative of Parietal Cell Loss
* In APCA-positive GPL cases, respectively of which PGI and the PGI/II ratio were significantly lower as compared to APCA-negative subjects.
* In APCA-positive GPL cases, the median G17 levels were significantly higher than in APCA-negative cases .
Table 3. Results of GastroPanel testing in patients with or without anti-parietal-cell antibodies.
* Divided the GPL patients into four groups, based on their history of H. pylori infection and APCA status (Figure 2A).
* G17, PGI and PGII levels are dependent on APCA positivity rather than the history of H. pylori infection.
* Investigated the diagnostic accuracy of GastroPanel in predicting AIG with an ROC analysis (Figure 2B & C)
* Diagnostic ability of PGII and H. pylori IgG was low, but PGI, the PG I/II ratio and G17 showed good diagnostic accuracy.
* Combining the PGI/II ratio and G17 : AUC increased to 0.884 (95% CI = 0.838–0.920) / sensitivity of 80.4% (95% CI = 66.1–90.6) and a specificity of 94.2% (95% CI = 90.2–97.0) - valuable supplementary tool in the detection of AIG among patients with GPL (Figure 2C)
Figure 2. Biomarker analysis for detection of autoimmune gastritis. (A) Serum level of PGI, PGII, PGI/II ratio, G17 and H. pylori IgG in patients with only autoimmune gastritis (AIG), patients with AIG and previous or active H. pylori infection, patients with only H. pylori infection and patients with no H. pylori infection or AIG. (B,C) Receiver operating characteristic (ROC) curve analysis of PGI, PGII, PGI/PGII ratio, G17 and H. pylori IgG for discrimination of patients with and without AIG.
<Discussion>
PG1, PGII and G17 measurement might be a reliable tool to help to identify AIG in patients with precancerous gastric lesions.
This study has real strengths. First, by prospectively following our cohort of patients with premalignant lesions, we were able to accurately link the presence of APCA to the course of disease. Secondly, this cohort is one of the largest prospective cohorts of patients with GPL to date and currently has a follow-up time of over 10 years.
Our data show that the prevalence of AIG is increased in patients presenting with GPL and may be subject to underdiagnoses. Awareness for AIG testing should be raised among both pathologists and gastroenterologists in order to optimize surveillance strategies.
<Abstract>
Background: Autoimmune gastritis (AIG), characterized with the presence of anti-parietal cell antibodies (APCA), is a risk factor for gastric cancer. However, AIG may go underdiagnosed, especially in the case of H. pylori infection and the presence of gastric precancerous lesions (GPL), due to the ambiguous pathology and delayed symptom onset.
Aim: Investigate the prevalence and characteristics of AIG in GPL patients.
Methods: Prevalence of AIG was determined with the presence of APCA in patients with GPL (n = 256) and the control group (n = 70). Pathological characteristics and levels of gastrin 17 (G17), pepsinogen (PG) I and II and anti-Helicobacter pylori IgG were assessed in GPL cases, and the severity of intestinal metaplasia and gastric atrophy was scored by expert pathologists.
Results: APCA positivity was observed in 18% of cases vs. 7% of controls (p = 0.033). Only 3/256 patients were previously diagnosed with AIG. The presence of APCA was associated with corpus-limited and extended GPL. A receiver operating curve analysis demonstrated that the G17 and PGI/II ratio could identify APCA-positive patients within GPL cases (AUC: 0.884).
Conclusions: The prevalence of AIG is higher in patients with GPL but goes undiagnosed. Using G17 and PG I/II as diagnostic markers can help to identify patients with AIG and improve surveillance programs for patients with GPL.
Keywords: autoimmune gastritis; gastric precancerous lesions; gastrin 17; pepsinogen
J Clin Med. 2023 Sep 23;12(19):6152. doi: 10.3390/jcm12196152.
* Strongest known risk factor for GC development is infection with the bacterium Helicobacter pylori (H. pylori)
* Endoscopic surveillance of gastric precancerous lesions (GPL) such as atrophic gastritis (AG) or intestinal metaplasia (IM) decreases the risk of developing invasive GC.
* Another cause of chronic gastritis is autoimmune gastritis (AIG), an immune-mediated disorder characterized with the destruction of gastric parietal cells.
* We investigated the prevalence of AIG in a prospectively followed cohort of patients with GPL.
* Clinical characteristics of AIG-associated IM and attempted to determine the diagnostic efficiency of gastric function biomarkers to optimize the detection of AIG in patients with GPL.
<Study populations>
* Prospective, multicenter study
* AIG-associated pathological features were re-evaluated in APCA-positive patients to confirm the diagnosis of AIG.
<Results>
1. Prevalence of AIG Is Increased in Patients with Gastric Premalignant Lesions
* APCA positivity was seen for 51 individuals, 36 of whom were women.
* A significantly higher prevalence of APCA positivity was seen in the GPL group as compared to the control cohort (18% vs. 7%, p = 0.033).
* The multivariable logistic regression analysis showed that APCA positivity (adjusted OR = 3.76, 95% CI = −1.31 to 10.79; p = 0.013), age (adjusted OR = 1.07, 95% CI = −1.04 to 1.09; p < 0.001) and male gender (adjusted OR = 0.47, 95% CI = −0.26 to 0.86; p = 0.015) were independently associated with IM.
Table 1. Baseline characteristics of study population and association between age, gender, APCA positivity, H. pylori infection history and GPL.
* Only three of the APCA-positive GPL cases were previously identified with AIG. (AIG may go underdiagnosed in patients with GPL)
* More than half of patients presented with low vitamin B12 levels (54.3%).
* Concomitant autoimmune disease was observed in 23.7% of cases (ATD: 19.5%).
* 19 presented with limited AG/IM lesions (44.2%, under surveillance according to the MAPSII guidelines )
2. AIG in GPL Patients Is Associated with Gastric Location, but Not Severity of GPL
* 51.2% (24/43) of APCA-positive patients have extended GPL, which is significantly more than in APCA-negative patients.
* Corpus involvement was more frequently identified in APCA-positive patients
* Antrum involvement was more frequently identified in APCA-negative subjects
Table 2. Distribution of precancerous lesion in the gastric mucosa of patients with or without anti-parietal-cell antibodies.
* OLGIM score was not affected by either APCA status (p = 0.16) or concentration of APCA (r = −0.06; p = 0.62; Figure 1A, C).
* OLGA score was lower in patients without APCA (p < 0.001).
* APCA levels did not correlate to severity of atrophy (r = 0.14; p = 0.31; Figure 1B,D).
Figure 1. Association between anti-parietal cell antibodies and severity of intestinal metaplasia and gastric atrophy. (A) No differences in Operative Link for Gastric Intestinal Metaplasia Assessment (OLGIM) stage were seen for cases with GPL positivity for anti-parietal cell antibodies (APCA) and those negative for APCA (p = 0.16). (B) Operative Link of Gastritis Assessment (OLGA) score of zero was more often seen for GPL cases without APCA (p < 0.001). (C) Serum concentration of APCA did not correlate with OLGIM score (r = −0.06; p = 0.62). (D) Serum concentration of APCA did not correlate with OLGA score (r = 0.14; p = 0.31).
* APCA was also compared to the worst OLGIM and OLGA score seen at any time during follow up, with similar results
Supplementary Figure S1. Serum concentration of APCA did not correlate with the worst OLGIM score detected during longitudinal follow-up (A, r=-0.1; p=0.39) or the worst OLGA stage (B, r=0.01; p=0.96).
3. AIG in the Context of Precancerous Gastric Lesions Is Associated with Serum Markers Indicative of Parietal Cell Loss
* In APCA-positive GPL cases, respectively of which PGI and the PGI/II ratio were significantly lower as compared to APCA-negative subjects.
* In APCA-positive GPL cases, the median G17 levels were significantly higher than in APCA-negative cases .
Table 3. Results of GastroPanel testing in patients with or without anti-parietal-cell antibodies.
* Divided the GPL patients into four groups, based on their history of H. pylori infection and APCA status (Figure 2A).
* G17, PGI and PGII levels are dependent on APCA positivity rather than the history of H. pylori infection.
* Investigated the diagnostic accuracy of GastroPanel in predicting AIG with an ROC analysis (Figure 2B & C)
* Diagnostic ability of PGII and H. pylori IgG was low, but PGI, the PG I/II ratio and G17 showed good diagnostic accuracy.
* Combining the PGI/II ratio and G17 : AUC increased to 0.884 (95% CI = 0.838–0.920) / sensitivity of 80.4% (95% CI = 66.1–90.6) and a specificity of 94.2% (95% CI = 90.2–97.0) - valuable supplementary tool in the detection of AIG among patients with GPL (Figure 2C)
Figure 2. Biomarker analysis for detection of autoimmune gastritis. (A) Serum level of PGI, PGII, PGI/II ratio, G17 and H. pylori IgG in patients with only autoimmune gastritis (AIG), patients with AIG and previous or active H. pylori infection, patients with only H. pylori infection and patients with no H. pylori infection or AIG. (B,C) Receiver operating characteristic (ROC) curve analysis of PGI, PGII, PGI/PGII ratio, G17 and H. pylori IgG for discrimination of patients with and without AIG.
<Discussion>
PG1, PGII and G17 measurement might be a reliable tool to help to identify AIG in patients with precancerous gastric lesions.
This study has real strengths. First, by prospectively following our cohort of patients with premalignant lesions, we were able to accurately link the presence of APCA to the course of disease. Secondly, this cohort is one of the largest prospective cohorts of patients with GPL to date and currently has a follow-up time of over 10 years.
Our data show that the prevalence of AIG is increased in patients presenting with GPL and may be subject to underdiagnoses. Awareness for AIG testing should be raised among both pathologists and gastroenterologists in order to optimize surveillance strategies.
<Abstract>
Background: Autoimmune gastritis (AIG), characterized with the presence of anti-parietal cell antibodies (APCA), is a risk factor for gastric cancer. However, AIG may go underdiagnosed, especially in the case of H. pylori infection and the presence of gastric precancerous lesions (GPL), due to the ambiguous pathology and delayed symptom onset.
Aim: Investigate the prevalence and characteristics of AIG in GPL patients.
Methods: Prevalence of AIG was determined with the presence of APCA in patients with GPL (n = 256) and the control group (n = 70). Pathological characteristics and levels of gastrin 17 (G17), pepsinogen (PG) I and II and anti-Helicobacter pylori IgG were assessed in GPL cases, and the severity of intestinal metaplasia and gastric atrophy was scored by expert pathologists.
Results: APCA positivity was observed in 18% of cases vs. 7% of controls (p = 0.033). Only 3/256 patients were previously diagnosed with AIG. The presence of APCA was associated with corpus-limited and extended GPL. A receiver operating curve analysis demonstrated that the G17 and PGI/II ratio could identify APCA-positive patients within GPL cases (AUC: 0.884).
Conclusions: The prevalence of AIG is higher in patients with GPL but goes undiagnosed. Using G17 and PG I/II as diagnostic markers can help to identify patients with AIG and improve surveillance programs for patients with GPL.
Keywords: autoimmune gastritis; gastric precancerous lesions; gastrin 17; pepsinogen