Analysis of clinical characteristics of 2243 with positive anti‐gastric parietal cell antibody

Abstract Background To facilitate the early detection of chronic diseases, we analyzed the clinical characteristics of anti‐gastric parietal cell antibody (PCA)‐positive population, revealed the early characteristics of the population. Methods According to the retrospective analysis, current situation investigation and comparative analysis of the clinical characteristics and medical history of the subjects, the comparison between the groups was performed. Result (a) The positive rate of PCA detection in department of gastroenterology in our hospital was 35.80%. Among the individuals who underwent PCA, esophagogastroduodenoscopy (EGD) and pathological examination at the same time, 33.59% of the patients with PCA positive were diagnosed as atrophic gastritis by gastroscopy, which was much higher than 9.09% of the patients with PCA negative. (b) The incidence of gastroesophageal reflux, hypertension, ischemic heart disease (IHD) and cerebral ischemia in PCA‐positive population were 65.45%, 81.63%, 15.43%, and 31.61%, respectively, which were significantly higher than those in the control group. (c) The incidence rates of decreased red blood cells (RBC) and increased homocysteine (HCY) in laboratory‐related tests were 38.30% and 69.15%, respectively, which were much higher than those in control group. Conclusion PCA has predictive value for a variety of chronic diseases and timely detection is of great significance.

Parietal cell antibody (PCA) is an important member of autoantibody family. PCA is an immunoglobulin secreted by plasma cells against H + /K + -ATP enzyme and gastrin receptor on the surface of gastric parietal cells. 2 Once the PCA antibody is produced, it reacts with its target antigen, causing progressive damage to gastric parietal cells and their functions. Finally, autoimmune atrophic gastritis (AAG) is formed, which affects its secretion of H + and internal factors, and the absorption of vitamin B 12 and folic acid.
Vitamin B 12 is a methyltransferase cofactor and an important material basis for the methylation of many substances and the redox reaction in vivo. It is involved in the metabolism of many important substances. The decrease in gastric acid secretion prevents the reduction of Fe3 + to Fe2 + in food. Hemoglobin synthesis disorder leads to iron deficiency anemia. Lack of vitamin B 12 and endocrine factors lead to obstruction of nucleic acid synthesis and cell mitosis, which eventually lead to pernicious anemia. When vitamin B 12 is deficient, the methionine circulation is blocked, and HCY cannot be converted into methionine and excreted out of the body, which results in the increase of plasma HCY level and eventually leads to H-type hypertension. Vitamin B 12 deficiency can also affect the metabolism of choline, epinephrine, norepinephrine, and other non-nutrients, and secondary to a variety of diseases. Therefore, PCA is the initiator of many chronic diseases and exists in the serum of patients before symptoms appear. Early detection is of great significance for the prevention and treatment of many chronic diseases.

| Subjects
PCA-positive group: In the past 5 years, PCA was detected in 6269 patients in the department of gastroenterology, with an average age of 57 ± 14 (age range 29-82), including 2780 males and 3489 females, male: female = 1:1.26. The standard for admission was the occurrence of one or more digestive system symptoms such as nausea, vomiting, anorexia, acid reflux, belching, abdominal pain, and abdominal distention and one or more digestive system diseases. PCA-negative group: According to the age and sex composition of the above group objects, 400 PCA-negative patients were stratified sampling, with an average age was 56 ± 12 (age range 27-81), including 180 males and 220 females, male: female = 1:1.22. The standard for admission was the occurrence of one or more digestive system symptoms such as nausea, vomiting, anorexia, acid reflux, belching, abdominal pain, and abdominal distention and one or more digestive system diseases.
Physical examination group: According to the age and sex composition of the above group objects, 400 cases of physical examination population were stratified sampling to detect PCA, with an average age was 55 ± 11 (age range 29-80), including 195 males and 205 females, male:female = 1:1.05.
There was no significant difference in the baseline characteristics of age and sex among the three groups.

| Research methods
The medical records of patients with PCA results were collected and analyzed from January 2015 to June 2019, and the clinical characteristics and medical history of PCA-positive patients were retrospectively analyzed and investigated, which compared with the control group.

| Detection methods
Parietal cell antibody was detected in venous serum by indirect immunofluorescence assay and operated strictly in accordance with the standard operating procedures. We took double-blind reading.
The titer of PCA > 100 was positive. Cerebral ischemia: A syndrome in which the blood supply of the brain is insufficient to meet the metabolic needs of the brain, resulting in a series of symptoms. Ischemic heart disease (IHD): The disease is caused by plaque building up along the inner walls of the arteries of the heart, which narrows the lumen of arteries and reduces blood flow to the heart.

| Statistical analysis
The qualitative indexes in logistic regression model were age, AIG, gastroesophageal reflux, coronary heart disease, cerebral ischemia, and sex. The quantitative indexes are blood pressure, RBC, and HCY value. According to the abovementioned criteria, the quantitative index is transformed into qualitative index.
A binary logistic regression analysis model is constructed to explore the relationship between AIG and related indicators. We describe the dependent variable as AIG and the independent variable as PCA, age, gastroesophageal reflux, hypertension, coronary heart disease, cerebral ischemia, decreased RBC, increased HCY, and gender.
Statistical analysis was performed using SPSS version 19.0 software (IBM Corp.). The difference was statistically significant with P < .01. The counting data of between groups were compared by chi-square test.

| Comparison of PCA-positive detection rate between the population in the department of gastroenterology and the physical examination population
Among the 6269 patients who were examined for PCA, 2243 were PCA positive. The positive detection rate was 35.80% (2243/6269), of which 1015 were male and 1228 were female, male: female = 1:1.21. PCA-positive rate was 11.25% (45/400) in 400 healthy people, which was much lower than that in the visiting population, χ 2 = 100.53, P < .01, (Table 1).

| Investigation and analysis of clinical symptoms and medical history in PCA-positive population
A retrospective analysis of clinical data of 2243 PCA-positive people revealed that the incidence of gastroesophageal reflux was higher, accounting for 1468/2243 = 65.45%; medical history of cerebrovascular diseases such as hypertension, IHD, and cerebral ischemia accounted for a higher proportion, 1831/2243 = 81.63%, 346/2243 = 15.43%, and 709/2243 = 31.61%, respectively, which was significantly higher than that of negative and physical examination control groups. The proportion of gastroesophageal reflux, hypertension, IHD, and cerebral ischemia in the negative group was significantly higher than that in the physical examination group (Table 3).

| Investigation on related Indexes of laboratory test in PCA-positive population
According to the investigation and analysis of blood routine test, liver function, and kidney function test items in 2243 PCA-positive people, it was found that the decrease in RBC and the increase in  tively, which were significantly higher than those in the negative control and physical examination group (Table 4).

| D ISCUSS I ON
The incidence of chronic gastritis in China is as high as 60%. 3 Chronic gastritis is divided into non-atrophic gastritis and atrophic gastritis according to morphological changes. However, due to the low attention of patients and the limitations of EGD and biopsy, the sensitivity of microscopic diagnosis of atrophic gastritis 4 was reduced, and the diagnosis was greatly delayed. How to make early diagnosis is a difficult problem in this field. Chronic atrophic gastritis can be divided into type A and B according to different etiologies. Type A atrophic gastritis-AAG, is the main type of atrophic gastritis. It is marked by the presence of autoantibodies such as PCA and anti-internal factor antibodies in serum. Early detection is very important for the early discovery of AIG. PCA is the initiator of type A atrophic gastritis. Studies have shown that PCA exists in the serum of patients earlier than the typical symptoms of the disease. 5 Literature studies have shown that PCA is an early marker of gastric mucosal atrophy. 6 In our study, we found that the In our study, the standard for admission was the occurrence of one or more digestive system symptoms in the population, so the current study did not analyze the common digestive system symptoms such as nausea, vomiting, anorexia, acid reflux, belching, abdominal pain, and abdominal distention. However, the incidence of gastroesophageal reflux is as high as 65.45%, which should cause high vigilance. This may be related to the abnormal peristalsis caused by hardening, inflammation, ulcer, and even atrophy of gastric body caused by PCA.
In our study, we found that the proportion of increased HCY in

Omnibus test of model coefficients
Step 1 Step is further affected, and a vicious cycle is formed. 11 Oral drug treatment for pernicious anemia is not effective, so it needs to be treated by intramuscular injection of vitamin B 12 for life. 12 It is reported that iron deficiency anemia occurs earlier than pernicious anemia, and vitamin B 12 has been deficient for many years before the occurrence of pernicious anemia. 13 There are also reports of regular intramuscular injection of vitamin B 12 to reduce the titer of PCA and alleviate related diseases. 14 It is confirmed that the level of vitamin B 12 is strongly correlated with the titer of PCA. In this survey, the percentage of decreased RBC in PCA-positive population is much higher than that in control group, which deserves great attention.
We should attach great importance to gastropathy, and the role of stomach as the first pass of human metabolism is very important. In this study, many kinds of chronic diseases caused by injury of digestive function that PCA induced were discussed and analyzed from the aspects of theoretical basis and clinical practice. We found that PCA is closely related to gastritis, especially type A atrophic gastritis, gastroesophageal reflux, and other digestive system diseases, as well as H-type hypertension, iron deficiency anemia, megaloblastic anemia, pernicious anemia, and other chronic diseases. The relationship between AIG and PCA was discussed by logistic regression analysis, and it was found that PCA was an independent risk factor for AIG. PCA appears in the serum of patients earlier than clinical symptoms, and early detection is of great value for early warning of a variety of chronic diseases. The detection of APC has little trauma and is widely used in clinic.
The limitation of this study is that there is no longitudinal follow-up survey of PCA-positive people. In this study, we found that most of the PCA-positive people could not be diagnosed as AIG by gastroscopy. This part of the population may develop into AIG as the disease progresses, which belongs to the potential population and needs further study.