JP5437062B2 - A method for determining gastric mucosal status by quantitative measurement of fecal Helicobacter pylori antigen - Google Patents

Description

  The present invention relates to a method for judging the state of gastric mucosa using a quantitative measurement value of Helicobacter pylori antigen present in feces as an index, and a method for quantifying the amount of Helicobacter pylori present in the stomach.

  Helicobacter pylori (hereinafter referred to as “Helicobacter pylori”, “Hp” or “H. pylori”) is a helical gram-negative bacterium present in the human gastric mucosa. The rate of human infection with Helicobacter pylori tends to increase with age, and is said to be as high as 70-80% in middle-aged and elderly people.

  In recent years, when Helicobacter pylori infects a healthy stomach, it first presents histological inflammation in the gastric mucosa and gradually becomes more severe (active gastritis), and eventually gastric mucosal atrophy (atrophic gastritis) ), And when gastric mucosal atrophy is advanced, intestinal metaplasia is thought to occur. There is also a lot of discussion about the relationship between the process of gastritis based on Helicobacter pylori infection and gastric cancer, and as the degree of gastric mucosal atrophy is milder, the degree of gastric cancer development increases. The risk rate is higher, and it is reported that the risk of developing gastric cancer is higher when intestinal metaplasia is observed than when no intestinal metaplasia is observed, and this tendency is particularly pronounced for differentiated gastric cancer. It has also been suggested (see Non-Patent Documents 1 and 2). Therefore, infection with Helicobacter pylori is considered not only a direct cause of gastritis, but also a risk factor for the development of gastric cancer. Currently, sterilization of Helicobacter pylori within health insurance is implemented when it is diagnosed as stomach ulcer and duodenal ulcer, and diagnosis of infection against Helicobacter pylori as a premise or result determination of this sterilization treatment Has been done. There are currently no sterilization treatments in health insurance for the prevention of diseases such as gastric ulcer, duodenal ulcer and gastric cancer, which are suggested to be related to Helicobacter pylori, and treatment of gastric cancer patients. Necessity is also discussed at academic societies.

  Methods for diagnosing Helicobacter pylori infection include invasive examinations that require endoscopy and tissue biopsy, and non-invasive methods that do not require them. The former includes rapid urease. Test (RUT), microscopy, and culture methods are used, and the latter uses urea breath test (UBT), anti-Helicobacter pylori antibody measurement, and fecal Helicobacter pylori antigen measurement.

  In addition to the fact that the burden on the subject is heavy in the invasive examination method, Helicobacter pylori is unevenly distributed in the stomach, and Helicobacter pylori cannot live in the gastric mucosa that has led to intestinal metaplasia Therefore, there is a problem that false negatives are likely to occur. On the other hand, although non-invasive testing can be performed relatively easily, UBT has high sensitivity and specificity, but it is false when a drug having an action of inhibiting urease activity is administered. There is a problem that negative is likely to occur, and in anti-Helicobacter pylori antibody measurement, it becomes negative in the early stages of infection, and conversely, it becomes positive immediately after sterilization, so accurate diagnosis cannot be performed depending on the test time There is a problem. In contrast, stool Helicobacter pylori antigen measurement detects Helicobacter pylori antigen present in feces excreted from the stomach via the digestive tract. This is excellent in that it is possible to directly evaluate the infection status (see Non-Patent Document 3). However, all of the above-mentioned test methods are used for the purpose of diagnosing the presence or absence of infection on the premise of sterilization therapy as described above or for judging the result of sterilization, Since there was no need to quantitate the amount of Helicobacter pylori, a method for quantifying the amount of bacteria present in the stomach has not been studied.

  On the other hand, endoscopy and pepsinogen method have been conventionally used as a method for diagnosing gastritis. Although endoscopy can make an accurate diagnosis for both the degree of inflammation and the type of gastritis, it is difficult for healthy subjects such as health checkups because it places a heavy physical burden on the subject and a large burden in terms of cost. It is unsuitable for use in the diagnosis of gastritis in a large population, and the pepsinogen method only measures the concentration of pepsinogen in the blood. In other words, there is a problem that active inflammation (active gastritis) that has not led to gastric mucosal atrophy cannot be evaluated.

Furthermore, a method for diagnosing atrophic gastritis by assaying for pepsinogen I, gastrin, and Helicobacter pylori infection markers has been proposed (see Patent Document 1), but Helicobacter pylori antigen is used as a Helicobacter pylori infection marker. In the case of use, a specific example is not described, and the cut-off value for diagnosis is not studied at all. Furthermore, a method for diagnosing the degree of atrophic gastritis and the degree of inflammation in gastritis without atrophy has not been studied.
Therefore, development of a method for diagnosing gastritis has been demanded, which can be easily performed with less burden on the subject and can be diagnosed by subdividing the degree of gastritis in detail.

  In addition, X-ray examination, pepsinogen method, and endoscopy are used in actual clinical practice as diagnostic methods for gastric cancer, risk factors for gastric cancer, or risk factors for future gastric cancer. Yes. X-ray examination is used for the detection of early gastric cancer, but there are many overlooked cases and there is a problem that it cannot be used for diagnosis of the risk of developing gastric cancer in the future. Other diagnostic methods such as pepsinogen method It is necessary to make a more accurate diagnosis in combination. The pepsinogen method is simple, but there are a certain percentage of cases that are missed, and there are cases of gastric cancer that cannot be detected when used in combination with X-ray examinations. Therefore, it is impossible to subdivide the degree of the risk factor to be determined, and it is impossible to determine the type of cancer (such as undifferentiated cancer or differentiated cancer). Furthermore, endoscopy can accurately diagnose not only gastric cancer but also gastric mucosa, which has a high risk of suffering from gastric cancer, but the burden on the subject is high and the cost is high. There is a drawback that it is unsuitable for primary screening for the population involved (see Non-Patent Document 4).

Further, in the method for diagnosing atrophic gastritis by assaying the above-mentioned pepsinogen I, gastrin, and Helicobacter pylori infection markers, there is also referred to diagnosis of cancer risk (see Patent Document 1). No specific examples of using Helicobacter pylori antigen as a H. pylori infection marker are described, and no judgment has been made on the determination of the type of cancer (undifferentiated cancer or differentiated cancer, etc.) .
Therefore, as a primary screening method for gastric cancer, it can be carried out easily with less burden on the subject, the rate of missed cases can be made as low as possible, and the risk of suffering from gastric cancer or the risk of suffering in the future As a method for diagnosing the rate, there has been a demand for the development of a method capable of diagnosing in detail the degree of risk rate and the type of gastric cancer having a high risk rate.

Kimihiko Yanagioka et al., Gastrointestinal Endoscopy, 2006, 18: 463-468 Kentaro Kanno and Nobuhiro Tsuji, “Evidence for Carcinogenesis of H. pylori”, Medical School, November 1, 2004, p6-13 and p20-29 Tomoko Kato et al., Helicobacter Research, 2006, 10: 404-410 Kazumasa Miki, “Pepsinogen Method Handbook”, Medical Review, March 2001, p10-27 and p50-52 JP-T-2004-517322

  Therefore, the problem of the present invention is that the burden on the subject can be easily implemented, and the proportion of missed cases is extremely small, the state of gastric mucosa with the disease state and its degree, the risk of suffering from gastric cancer or The object is to provide a method for determining the state of the gastric mucosa, which can be further subdivided in detail for the risk of suffering in the future. Another object of the present invention is to provide a method for quantifying the amount of Helicobacter pylori present in the stomach in relation to the determination of each disease state.

  In the course of diligent studies to solve the above-mentioned problems, the present inventors performed UBT (urea breath test), fecal Helicobacter pylori antigen measurement, and serum pepsinogen measurement for a large number of subjects. And its correlation, the amount of Helicobacter pylori present in the stomach of the subject can be quantitatively evaluated using as an index the quantitative measurement of Helicobacter pylori antigen present in the feces of the subject. As a result of further research based on this finding, we can easily and accurately determine the state of the gastric mucosa using the quantitative measurement of Helicobacter pylori antigen present in the stool of the subject as an index. The present invention has been completed.

That is, the present invention is a method for determining the state of the gastric mucosa of a subject using the quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject as an index , wherein the quantitative measurement value is an OD value. And an index of being 1.5 or more or less than 1.5 .
The present invention also relates to the method, wherein only the quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject is used as an index to determine the state of the subject's gastric mucosa.
The present invention further relates to the method, wherein the ratio of the concentration of pepsinogen I to the concentration of pepsinogen II in the blood of the subject is used as an indicator.
The present invention also relates to the method, wherein the ratio of the concentration of pepsinogen I to the concentration of pepsinogen II in the blood of the subject is 3 or less or exceeds 3.

Furthermore, the present invention relates to the method, wherein the gastric mucosa condition is at least one selected from mild, moderate or severe inflammation.
The present invention also relates to the above method, wherein the state of the gastric mucosa is at least one selected from mild, moderate or high atrophy.

The present invention further relates to the method as described above, wherein the state of the gastric mucosa is currently in a high risk state of suffering from gastric cancer.
The present invention also relates to the method, wherein the gastric cancer is undifferentiated gastric cancer or differentiated gastric cancer.
Furthermore, the present invention relates to the aforementioned method, wherein the state of the gastric mucosa is in a state with a high risk of suffering from stomach cancer in the future.
The present invention also relates to the method, wherein the gastric cancer is undifferentiated gastric cancer or differentiated gastric cancer.
Furthermore, the present invention relates to the above method, wherein the quantitative measurement value of Helicobacter pylori antigen is measured by an enzyme immunoassay using an antibody against Helicobacter pylori antigen.
The present invention also relates to the method, wherein the antibody against Helicobacter pylori antigen is a monoclonal antibody.

The present invention is a method for quantifying the amount of Helicobacter pylori bacteria present in the stomach of a subject using, as an index, a quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject , the quantitative measurement It is related with the said method including making a parameter | index that a value is 1.5 or more or less than 1.5 in OD value .
The present invention further relates to the above method, wherein the amount of Helicobacter pylori present in the stomach of the subject is quantified using only the quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject as an index.
The present invention also relates to the above method, wherein the quantitative measurement value of Helicobacter pylori antigen is measured by an enzyme immunoassay using an antibody against Helicobacter pylori antigen.
The present invention also relates to the above method, wherein the antibody against Helicobacter pylori antigen is a monoclonal antibody.
The method of the present invention uses the measured value of Helicobacter pylori antigen present in stool as an index, thereby monitoring the state of gastric mucosa that changes due to Helicobacter pylori infection and proliferation without time difference. This makes it possible to easily and accurately determine the state of the gastric mucosa.

According to the present invention, the total amount of Helicobacter pylori present in the stomach of a subject can be quantitatively evaluated only by quantitatively measuring the Helicobacter pylori antigen present in the stool of the subject.
In addition, according to the present invention, the state of the gastric mucosa of the subject can be determined with the quantitative measurement of fecal Helicobacter pylori antigen quantitatively reflecting the total amount of Helicobacter pylori in the subject's stomach as an index. It can be judged accurately. For example, gastric mucosal inflammation can be categorized in detail, from very minor inflammation immediately after onset to advanced inflammation, and a detailed decision is made from the perspective of gastric mucosal atrophy and inflammation. be able to. For the primary screening of gastric cancer, the false negative rate and the oversight rate are extremely low, so it is possible to make a highly reliable judgment, and the risk rate of suffering from gastric cancer, The degree and type of cancer can also be determined.

  Therefore, according to the present invention, a subject having gastric mucosal abnormalities such as inflammation, atrophy and gastric cancer can be found at an early stage, and only by measuring H. pylori antigen in the feces of the subject, Since it is not always necessary to perform endoscopy or blood collection, the burden on the subject can be greatly reduced compared to the conventional method. It is particularly excellent as a primary screening method for a large population.

  In addition, according to the present invention, it is possible to accurately determine the degree of inflammation and the degree of progression that could not be found by the conventional pepsinogen method even for a subject without atrophy. It is also possible to determine the risk of suffering from undifferentiated gastric cancer originating from gastritis or the risk of suffering in the future.

  And in the present invention, not only the quantitative measurement value of H. pylori antigen present in the stool of the subject, but also when using the ratio of the concentration of pepsinogen I to the concentration of pepsinogen II in the blood of the subject as an index, Since it is possible to determine the degree of atrophy in atrophic gastritis by subdividing it, gastric mucosa aging correlated with atrophy of the gastric mucosa that progresses with the natural course of chronic gastritis caused by Helicobacter pylori infection However, it is possible to judge by classifying the degree in detail. Therefore, it is possible to subdivide and determine the risk rate of suffering from gastric cancer, which is considered to increase with the degree of atrophic gastritis, and the state of high risk of suffering in the future. For those who have a high risk of disease, further endoscopy is performed to confirm the diagnosis of gastric cancer. It can be used to examine measures such as a typical management checkup.

  Further, according to the method of the present invention, the state of the gastric mucosa can be analyzed in a very short time without cost and without taking complicated procedures. For example, when the program according to the method of the present invention is prepared and used, the computer or the like only has a quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject, or further the concentration of pepsinogen II in the blood of the subject. The state of the gastric mucosa to be analyzed can be automatically output on a display such as a computer simply by inputting the ratio of the concentration of pepsinogen I to.

  Furthermore, according to the present invention, the state of the target gastric mucosa can be displayed as a point or the like on a straight line or a plane divided into the gastric mucosal state categories, so that From the condition of the compartment, the current state and future risks can be visually confirmed. In addition, in a subject whose gastric mucosa condition has been determined by the method of the present invention over time, the change over time of the point can also be indicated by a vector, so the degree of improvement or progress from the past, the future risk, etc. Can be easily grasped.

  That is, the present invention can determine the state of the gastric mucosa of the subject very accurately without imposing economic, time, and physical burden on the subject, and the degree of inflammation or atrophy of the subject, or suffering from stomach cancer. The method of judging the state of the gastric mucosa having such an effect was first realized by the present invention. Is.

The population of healthy Helicobacter pylori positive healthy individuals is divided into a group with a PGI / PGII of 3 or less and a group with a PGI / PGII of more than 3 in the scatter diagram with the fecal H. pylori antigen OD and UBT values as axes. FIG. In a scatter diagram with Helicobacter pylori-positive healthy individuals as axes of fecal H. pylori antigen OD and UBT values, there is a correlation between the two and a non-correlation group It is a figure divided and shown. It is a scatter diagram centering on the fecal H. pylori antigen OD value and PGI / PGII about the population of Helicobacter pylori positive healthy persons. In a scatter plot of Helicobacter pylori positive healthy individuals with the stool H. pylori antigen OD value and PGI / PGII as axes, there is a correlation between the stool H. pylori antigen OD value and the UBT value ( It is a figure divided and shown into the group (new population) with no correlation between a fecal H. pylori antigen OD value and UBT value. It is a scatter diagram centering on the fecal H. pylori antigen OD value and PGI about the population of Helicobacter pylori positive healthy individuals. It is a scatter diagram centering on the fecal H. pylori antigen OD value and PGII about the population of Helicobacter pylori positive healthy individuals. It is a scatter diagram centering on UBT value and PGI about a population of Helicobacter pylori positive healthy persons. It is a scatter diagram centering on UBT value and PGII about a population of Helicobacter pylori positive healthy persons. It is a scatter diagram centering on UBT value and PGI / PGII about a population of Helicobacter pylori positive healthy persons. In a scatter plot of Helicobacter pylori positive healthy individuals with stool H. pylori antigen OD values and PGI / PGII as axes, categories I to IV and fecal H. pylori antigen OD value 0.1 It is a figure which divides and shows less than PGI / PGII on the basis of 3. The population of healthy Helicobacter pylori positive healthy individuals is divided into 4 groups of categories I to IV regarding gastric mucosal state in the scatter diagram with the fecal H. pylori antigen OD value and PGI / PGII as axes. It is a figure which shows the type of the risk rate and the risk rate which will be affected in the future, or the future disease. The population of healthy Helicobacter pylori positive individuals is divided into 4 groups of categories I to IV regarding gastric mucosal state in the scatter diagram with the fecal H. pylori antigen OD value and PGI / PGII as axes. It is a figure which shows the example of a preventive / therapeutic measure based on the risk rate to suffer from stomach cancer in the future. It is a figure which shows the relationship between the category I-IV and PGI value which classify | categorized using the fecal H. pylori antigen OD value and PGI / PGII as a parameter | index. It is a figure which shows the relationship between the category I-IV and PGII value which classified using the fecal H. pylori antigen OD value and PGI / PGII as a parameter | index. It is a figure which shows the typical example of transition of the Helicobacter pylori infectious gastritis.

  According to the present invention, using the quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject as an indicator, the method for quantifying the amount of Helicobacter pylori present in the stomach of the subject and the gastric mucosa of the subject A method for determining a state is provided.

  In the present invention, “subject” means any living individual, preferably a vertebrate, more preferably a mammal, and even more preferably a human individual. In the present invention, the subject may be healthy or may have some kind of disease.

  The quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject used as an index in the method of the present invention is a continuous numerical value according to the amount of Helicobacter pylori antigen present in the stool of the subject. As long as it is obtained by the obtained measurement method, it may be obtained using any measurement method, for example, an enzyme immunoassay (EIA) using an antibody against Helicobacter pylori antigen, Measured values obtained by known methods such as radioimmunoassay (RIA) or fluorescence immunoassay can be used. Among these, enzyme immunity is used from the viewpoint of ease of operation. A measurement value measured by using a measurement method is particularly preferable.

  As an antibody against Helicobacter pylori antigen (hereinafter also referred to as “anti-Helicobacter pylori antigen antibody”) used in the method of the present invention, a polyclonal antibody or a monoclonal antibody may be used. Monoclonal antibodies are preferably used from the viewpoints of specificity for and reproducibility of results. An antibody against Helicobacter pylori antigen is, for example, in feces in a state where Helicobacter pylori urease, heat shock protein or catalase, live Helicobacter pylori, dead Helicobacter pylori or fragments thereof can be antigens. Since they exist, these can be used as antigens by known antibody production methods.

An enzyme immunoassay using an antibody against Helicobacter pylori antigen can be performed, for example, as follows;
First, an anti-Helicobacter pylori antigen antibody is bound in advance to a solid phase such as a well of a microplate or a plastic tube, a sample (diluted solution of the target stool) is added thereto, and the Helicobacter pylori antigen in the sample is added. Is bound to the solid phase by an antigen-antibody reaction. Next, after washing away impurities, an enzyme-labeled second antibody (anti-Helicobacter pylori antigen antibody) was added and the “anti-solid antibody / Helicobacter pylori antigen / enzyme-labeled antibody” sandwich was performed again by antigen-antibody reaction. Let the structure build. Here, the free enzyme-labeled antibody is washed away, and a chromogenic substrate is added to cause a chromogenic reaction proportional to the amount of sandwich structure (ie, the amount of Helicobacter pylori antigen in the sample). Thereafter, the amount of the color developing substance produced is read with an absorptiometer or the like, and the obtained absorbance or the like is used as a measurement value.

  As an enzyme used for labeling the above-mentioned anti-Helicobacter pylori antigen antibody, for example, peroxidase, alkaline phosphatase, β-galactosidase, glucose oxidase and the like can be used. The enzyme labeling of the antibody can be appropriately performed by a known method such as a maleimide method. Further, when peroxidase is used as the chromogenic substrate as the above enzyme, 3,3′-5,5′-tetramethylbenzidine, 2,2′-azino-bis (3-ethylbenzothiazoline)- When alkaline phosphatase is used as the above enzyme such as 6-sulfonic acid (ABTS), luminol, or o-phenylenediamine, p-nitrophenyl phosphate, methylumbelliferyl phosphate, or 3- (2′-spiro) When β-galactosidase is used as the above enzyme, such as adamantane) -4-methoxy-4- (3 ″ -phosphoryloxy) phenyl-1,2-dioxetane, p-nitrophenyl-β-D-galactoside, Alternatively, methylumbelliferyl-β-D-galactoside can be used. .

  Kits for measuring Helicobacter pylori antigens present in feces by enzyme immunoassay include “Testmate Pylori Antigen EIA” (Wakamoto Pharmaceutical Co., Ltd./Kyowa Medex Co., Ltd.), “Meridian HpSA ELISA” (Meridian Bioscience) Inc./TEF) are commercially available and can be used for quantitative measurement of Helicobacter pylori antigen in the present invention. "Testmate H. pylori antigen EIA" is a monoclonal antibody as an anti-Helicobacter pylori antigen antibody. Is used particularly preferably in the present invention.

  In the present invention, “determining the state of the gastric mucosa of the subject” means that the state of the gastric mucosa of the subject is normal, exhibits inflammation, or chronic gastritis (active gastritis, atrophic gastritis), This means that the risk of suffering from gastric cancer or a high risk of suffering in the future is judged, and if there is inflammation, the degree of inflammation is further reduced to mild or moderate. It is possible to judge by classifying highly, whether the type of chronic gastritis is active gastritis or atrophic gastritis, and if it is classified as active gastritis or atrophic gastritis, inflammation and atrophy The degree (progression level) can be divided into light, moderate, and highly subdivided. For gastric cancer, the risk of suffering from undifferentiated or differentiated gastric cancer is high, and if not, it is possible to determine the risk of suffering from each cancer in the future. is there. Furthermore, it is also possible to set classifications that are further subdivided and make a judgment according to the classification.

In the present invention, inflammation of gastric mucosa refers to inflammation observed in all cases of gastric mucosa infected with Helicobacter pylori and having neutrophil infiltration.
Further, in the present invention, chronic gastritis refers to chronic gastritis with a high onset frequency according to aging, which was conventionally considered an aging phenomenon, but has recently been found to be caused by Helicobacter pylori. It is classified into active gastritis and atrophic gastritis.

Furthermore, active gastritis means chronic gastritis with increased inflammation due to persistent infection with Helicobacter pylori, and atrophic gastritis refers to chronic gastric mucosal atrophy caused by persistent infection with Helicobacter pylori. Means gastritis. Here, gastric mucosal atrophy refers to a state in which the gastric gland that secretes gastric acid is reduced, and atrophy occurs through inflammation of the gastric mucosa by Helicobacter pylori, and it is known that atrophy progresses over time. It has been.
Intestinal metaplasia refers to a tissue structure peculiar to the gastric mucosa, that is, a mucosa that has changed to a state similar to the intestinal mucosa due to loss of the gastric intrinsic glands that secrete gastric acid.

  Further, in the present invention, differentiated gastric cancer is a gastric cancer having a structure close to the original gastric mucosa, and is characterized by the fact that when the symptoms progress, it grows like a lump and easily metastasizes to the liver. . It is a cancer often found in the elderly, with atrophic gastritis as the origin, and is said to have good prognosis. Undifferentiated gastric cancer is a gastric cancer that has a structure that is far from the original gastric mucosa, has no distinct boundaries, grows in a dispersed state of cancer cells, and has many features of metastasis to lymph nodes Refers to cancer with It is a cancer found in young people and is said to have a poor prognosis due to active gastritis.

  The risk of developing gastric cancer is currently not affected by gastric cancer, but if the subject's current state of gastric mucosa is maintained in the future, It is judged on the basis of whether it is statistically higher or lower than that in the better gastric mucosa state. Therefore, subjects with intestinal metaplasia have a higher risk of developing gastric cancer than subjects without it, and subjects with gastric mucosal atrophy have a higher risk of developing gastric cancer as the degree of atrophy increases. It is known that subjects with high and high levels of inflammation are at a higher risk of developing gastric cancer than subjects without it. Whether or not it is atrophic gastritis, the extent of these gastritis, and whether or not they have intestinal metaplasia The risk factor can be determined.

Specific embodiments of the present invention are described below.
A procedure for performing quantitative measurement of Helicobacter pylori antibody present in the stool of the subject will be briefly described, for example, in the case of using the above-mentioned “Testmate H. pylori antigen EIA”.
From each subject's stool collection container, 1 drop (50 μl) of stool dilution was added to a 96-well microplate on which anti-Helicobacter pylori native catalase mouse monoclonal antibody (21G2) was immobilized, and peroxidase-labeled anti-Helicobacter pylori. native Add 50 μl of catalase mouse monoclonal antibody (21G2) solution and react for 1 hour. Next, each well was washed 5 times with a washing solution to remove unreacted substances. After adding 100 μl of a substrate solution (hydrogen peroxide and tetramethylbenzidine) and reacting for 10 minutes, a reaction stop solution (0.5 mol / ml) was added. l sulfuric acid) is added to stop the reaction, and the absorbance (450 nm / 630 nm) is measured with a microplate reader.

  When judging the state of the gastric mucosa of the subject using only the quantitative measurement value of Helicobacter pylori antigen present in the stool of the subject as an index, the OD value obtained by the measurement using the kit (hereinafter simply referred to as “OD value”). The lower the value, the milder the inflammation, and the higher the OD value, the more severe the inflammation. Although there may be some differences depending on the type of the target population, such as race, age, and sex, for example, when the OD value is 0 or more and less than 0.1, normal gastric mucosa, 0.1 or more, and 1. A case of less than 5 can be judged as mild active gastritis, and a case of 1.5 or more can be judged as moderate to highly active gastritis. In addition, the higher the OD value, the higher the inflammation and the higher the progression of active gastritis.

Regarding gastric cancer, for example, when the OD value is 1.5 or more, it may be determined that the state of the gastric mucosa is in a state of high risk of suffering from gastric cancer or high risk of suffering in the future. it can.
According to the above-mentioned classification of gastritis, considering the relationship between each gastritis state and gastric cancer, for example, the risk rate of suffering from undifferentiated gastric cancer when the OD value is 1.5 or more It can be determined that the unaffected person has a high risk of suffering in the future.

  Furthermore, the quantitative measurement of Helicobacter pylori antigen present in the feces of the subject and the ratio of the concentration of pepsinogen I (PGI) to pepsinogen II (PGII) in the blood of the subject (hereinafter referred to as “PGI / PGII”) The state of the gastric mucosa of the subject can be determined using the notation) as an index. When PGI / PGII is a predetermined value or less, for example, 3 or less, atrophic gastritis is considered. In atrophic gastritis, the higher the OD value, the stronger the inflammation and the lower the PGI / PGII, the extent of atrophic gastritis (progression) The degree of) will also be advanced. Furthermore, it can be determined that the lower the OD value and the lower the PGI / PGII, the weaker the inflammation and the higher the degree of atrophic gastritis (the degree of progression) and the higher the possibility of intestinal epithelialization.

  Further, when PGI / PGII exceeds a predetermined value, for example, 3, since gastric mucosal atrophy does not occur, the higher the OD value, the higher the inflammation and the higher the extent of active gastritis. It can be determined that the lower the OD value, the milder the inflammation and the closer it is to normal.

  Further, when the OD value is 0 or more and less than 0.1 and PGI / PGII exceeds 3, it is judged as normal gastric mucosa, and the OD value is 0.1 or more and less than 1.5 and PGI / PGII is 3 If the OD value exceeds 1.5, the OD value is 1.5 or more and the PGI / PGII exceeds 3 can be determined as moderate to high inflammation. For the group of PGI / PGII ≦ 3 with atrophy, if the OD value is 1.5 or more and the PGI / PGII is 3 or less, atrophic gastritis accompanied by severe inflammation, and the OD value is less than 1.5 and PGI / If PGII is 3 or less, it can be judged as atrophic gastritis with mild to moderate inflammation. When the OD value is less than 1.5 and PGI / PGII is 3 or less, the lower the OD value and PGI / PGII, the higher the possibility of having intestinal metaplasia.

  In addition, when the gastric mucosa is cancer, according to the classification of gastritis described above, considering the relationship between each gastritis and cancer, for example, the OD value is less than 1.5 and PGI / If the PGII exceeds 3, the risk of suffering from stomach cancer or the risk of suffering from the future is very low, while if the OD value is 1.5 or more or the PGI / PGII is 3 or less, the person is suffering from stomach cancer. It can be determined that the risk factor is high and the risk factor of suffering in the future is high even if the patient is not suffering from stomach cancer. Further, when the OD value is 1.5 or more and PGI / PGII exceeds 3, when the OD value is 1.5 or more and PGI / PGII is 3 or less, the OD value is less than 1.5 and PGI / PGII. The risk of suffering from gastric cancer or the risk of suffering in the future increases in the order of 3 or less, especially when the OD value is less than 1.5 and PGI / PGII is 3 or less, it can be judged as high risk . In addition, when the OD value is 1.5 or more, the type of gastric cancer at that time can be determined to be in a state where the risk of suffering from undifferentiated gastric cancer or the risk of suffering from the future is high. When the OD value is less than 1.5 and PGI / PGII is 3 or less, it can be determined that the risk of suffering from differentiated gastric cancer or the risk of suffering from the future is high.

In the present invention, as described above, typically, the state of the gastric mucosa of the subject is determined by “using 3 as the reference value for PGI / PGII” and “using 1.5 as the reference value for the OD value”. As described above, depending on the type of the target population such as race, age, and sex, or the purpose of determining the gastric mucosal state such as screening of missed cases by the PG method, PGI / PGII 2 A predetermined value of ˜3 can be used as a reference value, and a predetermined value of 1.5 to 2.0 can be used as a reference for the OD value. A specific example will be described in detail in Example 2 described later.
In addition to PGI / PGII, age and other test values (PGI concentration in blood, PGII concentration in blood, anti-CagA antibody concentration in blood), subjective symptoms (upper abdominal pain, stomach upset, heartburn, The presence or absence of nausea / nausea, abdominal bloating, etc.) may be added as an index, and these indices can be used to classify in more detail.

  In addition, although the example of said OD value is an example when all use "test mate H. pylori antigen EIA", also when performing the quantitative measurement of Helicobacter pylori using "Meridian HpSA ELISA", It is possible to make judgments in the same numerical range. In addition, when the Helicobacter pylori antigen is quantitatively measured without using the above two kits, for example, when the absorbance is used as a measurement value by an enzyme immunoassay, it can be quantitatively detected. By performing numerical correction to correspond the range of the lower limit value to the upper limit value to the range of the lower limit value to the upper limit value of the absorbance when using the above-mentioned “Testmate H. pylori antigen EIA”, the same numerical range as above In addition, when radioimmunoassay or fluorescence immunoassay is used, the range of the lower limit measurement value to the upper limit measurement value that can be quantitatively detected should correspond to the above numerical range. Thus, it is possible to set a numerical range similar to the above.

  Further, according to the method of the present invention, the amount of Helicobacter pylori present in the stomach of the subject is quantitatively evaluated from the quantitative measurement value of the Helicobacter pylori antigen present in the stool of the subject. For example, when the above-described kit “Testmate Pylori Antigen EIA” is used, it can be evaluated that the amount of Helicobacter pylori in the stomach increases as the measured absorbance increases. According to the OD value when the kit is used, for example, if the OD value is 0 or more and less than 0.1, it is judged that there is no Helicobacter pylori in the stomach, and if it is 0.1 or more and less than 1.5. It can be determined that the amount of Helicobacter pylori in the stomach is small, and if the amount is 1.5 or more, the amount of Helicobacter pylori in the stomach is large. It is also possible to make a judgment by further subdividing such classification. According to the method of the present invention, it is possible to directly monitor the variation in the amount of bacteria in a subject when a preventive measure or treatment is performed.

The present invention will be described more specifically with reference to the following examples, but the scope of the present invention is not limited to these examples.
<Example 1>
UBT (urea breath test), fecal Helicobacter pylori antigen measurement, blood pepsinogen (PGI and PGII) concentration, blood anti-antibiosis for 104 healthy subjects (36 men, 68 women) who are positive for Helicobacter pylori The CagA antibody concentration was measured.
UBT (urea breath test) was performed using Ubit tablets (Otsuka Pharmaceutical Co., Ltd.), and fecal Helicobacter pylori antigen measurement was performed using “Testmate Pylori antigen EIA”. An OD value of 0.1 or more was determined to be positive by measuring fecal Helicobacter pylori antigen.

The table below shows the number of 104 people targeted by age group.

(1) Examination of the relationship between the quantitative measurement value of the fecal Helicobacter pylori antigen and the UBT value First, the quantitative measurement value obtained by the fecal Helicobacter pylori antigen measurement (hereinafter, “ In order to examine the relationship between the stool H. pylori antigen OD value) and the UBT value, a group of PGI / PGII> 3 in which gastric mucosal atrophy is absent and PGI in which gastric mucosal atrophy is present / PGII ≦ 3 and a scatter diagram is prepared (FIG. 1), and the correlation coefficient between the fecal H. pylori antigen OD value and UBT value is calculated using the above PGI / PGII> 3 population. And PGI / PGII ≦ 3. The results are shown in Table 2.

  From Table 2, a significant correlation is observed between the stool H. pylori antigen OD value and UBT value in the PGI / PGII> 3 group, but no correlation is observed in the PGI / PGII ≦ 3 group. It was shown that.

  Conventionally, it has been considered that the amount of Helicobacter pylori in the stomach is reduced by gastric mucosal atrophy, and in fact, in FIG. 1, the UBT value tends to be low in the group of PGI / PGII ≦ 3 having gastric mucosal atrophy. On the other hand, in the population with PGI / PGII ≦ 3, it was found that there is a population with a high fecal H. pylori antigen OD value even though the UBT value is low. This population is a population in which there is no correlation between the fecal H. pylori antigen OD value and the UBT value, and it can be said that this population was discovered for the first time by the present invention, and PGI / PGII ≦ 3. The population could be classified on the basis of having a fecal H. pylori antigen OD value of 1.5 or more.

  Furthermore, when a correlation is observed between a stool H. pylori antigen OD value and a UBT value, a group in which a correlation is not recognized and a group in which a correlation is not recognized are separately shown on a scatter diagram (FIG. 2). From the conventional knowledge that the diagnosis of infection with Helicobacter pylori by the measurement of Helicobacter pylori antigens and the diagnosis of infection with Helicobacter pylori by UBT are consistent, a new population (fecal Helicobacter pylori antigen OD value and UBT We were able to find a group with no correlation between the values.

(2) Examination of relationship between fecal H. pylori antigen OD value and PGI / PGII Next, in order to examine the relationship between fecal H. pylori antigen OD value and PGI / PGII, When prepared (FIG. 3), it was found that the population having gastric mucosal atrophy (PGI / PGII ≦ 3) includes a population having a high fecal H. pylori antigen OD value. Therefore, contrary to the conventional finding that gastric mucosal atrophy reduces the amount of Helicobacter pylori in the stomach, it was suggested that even if gastric mucosa atrophy is present, there is a population with a large amount of Helicobacter pylori in the stomach.
Also, in FIG. 3, as in FIG. 2 of (1) above, a group with a correlation and a group with no correlation are shown separately on a scatter diagram (FIG. 4). The new population found in (1) “no correlation between fecal H. pylori antigen OD value and UBT value” is a stool in the population having gastric mucosal atrophy (PGI / PGII ≦ 3). It was revealed that the OD value of H. pylori antigen was particularly prominent in a population having an OD value of 1.5 or more.

(3) Examination of relationship between fecal H. pylori antigen OD value and PGI value or PGII value Further, in order to investigate the relationship between fecal H. pylori antigen OD value and PGI value or PGII value, (FIGS. 5 and 6), and the correlation coefficient between the fecal H. pylori antigen OD value and the PGI value, or the fecal H. pylori antigen OD value and the PGII value was calculated (Tables 3 and 4).

  Pepsinogen (PG) is a precursor of pepsin and is originally secreted into the stomach lumen and converted to pepsin to act as a proteolytic enzyme, but about 1% of PG is found in blood. PG is immunologically divided into PGI and PGII, and the distribution in each stomach is different. PGI is present in the fundus gland region (main cells and accessory cells), and PGII is also widely present in the cardia gland, pyloric gland and Brunner gland. It is known that the concentration in the blood changes due to the difference in the distribution of the two, reflecting the state of the gastric mucosa. In particular, it is suggested that PGI / PGII is low in correlation with the progress of atrophy. However, it is known that the PGI value and the PGII value alone reflect inflammation and atrophy of the gastric mucosa. If the PGI and PGII values are high, such as when the PGI value exceeds 70 and the PGII value exceeds 20, it can be explained that inflammation is high.

  As understood from Table 3, no significant correlation was observed between the fecal H. pylori antigen OD value and the PGI value. On the other hand, as understood from Table 4, it was found that a significant correlation was observed between the fecal H. pylori antigen OD value and the PGII value. Since the PGII value is known to show a positive correlation with the degree of inflammation of the gastric mucosa, the fecal H. pylori antigen OD value is found to be an index representing the degree of inflammation of the gastric mucosa, Furthermore, since it is known that the degree of inflammation of the gastric mucosa increases with an increase in the amount of Helicobacter pylori in the stomach, the fecal H. pylori antigen OD value is an index representing the amount of Helicobacter pylori in the stomach I also discovered that

(4) Examination of relationship between UBT value and PGI value or PGII value In the same manner as in (4) above, in order to examine the relationship between UBT value and PGI value or PGII value, a scatter plot of the above 104 groups of people was used. The correlation coefficient was calculated (Figs. 7 and 8). Unlike the case of stool H. pylori antigen OD value, both UBT value and PGI value, and between UBT value and PGII value were significant. No significant correlation was found.

(5) Examination of relationship between UBT value and PGI / PGII Next, in order to examine the relationship between UBT value and PGI / PGII, a scatter diagram of the above-mentioned group of 104 people was created (FIG. 9). In the population with atrophy (PGI / PGII ≦ 3), it was found that the UBT value decreased as PGI / PGII decreased. This is because the UBT value detects the activity of Helicobacter pylori urease. As the gastric mucosal atrophy progresses and the PGI / PGII value decreases, the gastric acid secretion decreases and the gastric pH decreases. This is thought to be because the urease activity of Helicobacter pylori decreased.
Therefore, it is understood that the UBT value does not serve as an index of the amount of Helicobacter pylori existing in the stomach when gastric mucosal atrophy is exhibited (PGI / PGII ≦ 3).

  From the above results, it is suggested that fecal H. pylori antigen OD value is an index that represents the degree of inflammation of the gastric mucosa, and that it is an index that quantitatively represents the amount of H. pylori present in the stomach, In particular, in the case of gastric mucosal atrophy (PGI / PGII ≦ 3), it can be seen that the indicator that quantitatively represents the amount of H. pylori present in the stomach is not the UBT value but the stool H. pylori antigen OD value. It was issued. Furthermore, conventionally, it was thought that the amount of H. pylori in the stomach decreases with gastric mucosal atrophy, but the fecal H. pylori antigen OD value is high in the population with gastric mucosal atrophy (PGI / PGII ≦ 3) ( The fecal H. pylori antigen OD value ≧ 1.5) The discovery of a new population suggested for the first time that there was a population with a high amount of H. pylori in the stomach even with gastric mucosal atrophy.

(6) Examination of clinical significance of classification based on fecal H. pylori antigen OD value As described above, it was found that the population could be statistically classified on the basis of 1.5 regarding fecal H. pylori antigen OD value. From the above, 104 healthy subjects positive for Helicobacter pylori targeted in this Example were divided into a group of 1.5 or more and a group of less than 1.5 with respect to the fecal H. pylori antigen OD value, and their PGI and PGII values. From the distribution of this range, it was examined how the fecal H. pylori antigen OD value corresponds to a specific gastric mucosal state. The PGI values are classified into four groups: PGI value ≦ 30, 30 <PGI value ≦ 50, 50 <PGI value ≦ 70, and 70 <PGI value. The PGII value is classified as PGII value ≦ 10, 10 <PGII value ≦ It was classified into three, 20, 20 <PGII value. The results are shown in Table 5 below.

According to Table 5, the proportion of stool H. pylori antigen OD value of 1.5 or more is high in the proportion of subjects whose PGI value and PGII value are both high, such as 70 <PGI value, 20 <PGII value. It is understood that this is a population with a high degree of inflammation of the gastric mucosa. On the other hand, the population whose fecal H. pylori antigen OD value is less than 1.5 is lower than the population whose fecal H. pylori antigen OD value is 1.5 or more. It is understood that this is a population with a high proportion and a low degree of inflammation of the gastric mucosa.
Further, from Table 6, when the PGI value and the PGII value were compared for the two populations of the population having a fecal H. pylori antigen OD value of less than 1.5 and a population of 1.5 or more, it was statistically significant with respect to the PGII value. The difference was able to be confirmed.
Therefore, it was shown that classification based on the fecal H. pylori antigen OD value of 1.5 is clinically significant.
Table 6 also shows the case where the reference value of the OD value is 2.0, but the same result as in the case of 1.5 was obtained. That is, when the PGI value and the PGII value were compared for two populations, a population having a fecal H. pylori antigen OD value of less than 2.0 and a population of 2.0 or more, a statistically significant difference was confirmed regarding the PGII value. We were able to.

(7) Classification of gastric mucosal state using stool Helicobacter pylori antigen OD value and PGI / PGII as indicators Index of stool H. pylori antigen OD value is 1.5, and whether PGI / PGII is atrophy Based on 3 as an index, 104 healthy subjects with positive Helicobacter pylori targeted in this example were classified as Category I (fecal H. pylori antigen OD value of 0.1 to less than 1.5 and PGI / PGII Greater than 3), category II (fecal H. pylori antigen OD value greater than 1.5 and PGI / PGII greater than 3), category III (fecal H. pylori antigen OD value greater than 1.5 and PGI / PGII greater than 3) 3 or less) and Category IV (fecal H. pylori antigen OD value is 0.1 or more and less than 1.5 and PGI / PGII is 3 or less) (FIG. 10). ).

Category I is a population having a fecal H. pylori antigen OD value of 0.1 or more and less than 1.5 and a PGI / PGII of greater than 3, and is associated with mild gastritis with mild inflammation without gastric mucosal atrophy. Considered a group.
Category II is a group of active gastritis that has moderate to high inflammation with no gastric mucosal atrophy, and is a population with a fecal H. pylori antigen OD value of 1.5 or more and PGI / PGII greater than 3. it is conceivable that. Within Category II, it is considered that the degree of active gastritis progresses (becomes higher) as the fecal H. pylori antigen OD value increases.

  Category III is a group having a fecal H. pylori antigen OD value of 1.5 or more and PGI / PGII of 3 or less, and is considered to be a group of atrophic gastritis combined with highly active inflammation. Within Category III, the higher the OD value, the stronger the inflammation and the lower the PGI / PGII, the more atrophic gastritis is considered to progress (become higher).

Category IV is a population having a fecal H. pylori antigen OD value of less than 1.5 and a PGI / PGII of 3 or less, and is considered to be a population of atrophic gastritis with mild to moderate inflammation. Within Category IV, the lower the fecal Helicobacter pylori antigen OD value and PGI / PGII, the higher the possibility of having intestinal metaplasia and progressing to the most advanced atrophic gastritis (higher) Is considered.
In order to classify the state of the gastric mucosa as healthy, the fecal H. pylori antigen OD value must be less than 0.1 and PGI / PGII must be greater than 3.

When infected with Helicobacter pylori, category I, II, III, IV, OD value is less than 0.1 and PGI / PGII is 3 or less in order of the state of gastric mucosa with the passage of time, That is, it is considered that the aging of the gastric mucosa proceeds.
Furthermore, regarding the categories I to IV, the average values of PGI / PGII, fecal H. pylori antigen OD value, PGI value, and PGII value are shown in Table 7 below.

  Furthermore, the classification of the above categories I to IV and the degree of risk of suffering from stomach cancer and the degree of risk of suffering in the future will be described. According to the above classification, considering the relationship between each gastritis condition and cancer, the population with an OD value <0.1 and PGI / PGII> 3 and category I are the risk factors and future morbidity for gastric cancer. Therefore, it can be determined that the risk factor is extremely low. Categories II, III, IV and populations with OD values <0.1 and PGI / PGII ≦ 3 are at risk of suffering from gastric cancer and are at high risk of suffering in the future even if no gastric cancer has occurred It can be judged that there is. The risk of suffering from gastric cancer or the risk of suffering in the future increases in the order of categories II, III, IV and OD values <0.1 and PGI / PGII ≦ 3, especially category IV and OD values <0.1 And the group of PGI / PGII ≦ 3 can be judged as a high risk. In addition, the types of gastric cancer can be determined to be in a state of high risk of suffering from undifferentiated gastric cancer or high risk of suffering from undifferentiated gastric cancer in category II and III, and IV and OD values <0.1. In addition, it can be determined that the population with PGI / PGII ≦ 3 is at a high risk of suffering from differentiated gastric cancer or a risk of suffering in the future. Therefore, in the primary screening of gastric cancer, it is possible to efficiently lead to early detection of gastric cancer by performing a definitive diagnosis by endoscopy for the risk group shown in FIG. 11, particularly the high risk group. Also, for those who do not suffer from stomach cancer, as shown in FIG. 12, for example, subjects included in categories II and III are instructed to undergo active prevention and regular management screening. For subjects included in Category IV and OD values <0.1 and PGI / PGII ≦ 3, take thorough periodic management checkups and take specific measures such as implementing sterilization treatment. Is possible.

Moreover, regarding each of the above classifications (category I to IV) of the state of gastric mucosa using stool Helicobacter pylori antigen OD value and PGI / PGII as indices, the relationship with PGI value or PGII value was examined (FIG. 13 and FIG. 13). 14).
As shown in Table 8, when comparing Category III and Category IV, in which a group judged to have atrophic gastritis with a PGI / PGII of 3 or less and a fecal H. pylori antigen OD value of 1.5, Category III PGII is It was statistically significantly high, confirming that inflammation was high. In addition, a statistically significant difference was confirmed between Category II and Category III PGII. Thus, the classification from category I to category IV was shown to be clinically significant.

<Example 2>
As shown in FIG. 15, the progression of Helicobacter pylori infectious gastritis typically changes to vestibular dominant gastritis, pangastritis, and body dominant gastritis (Vestibular dominant gastritis is a type that is common in Westerners, Pangastritis and body-dominated gastritis are common among Japanese over 40 years old). 200 adults (94 men, 104 women, average age 55 years (22-84 years)) to elucidate the relationship between each stage of gastritis progression and fecal Helicobacter pylori antigen OD levels In the same manner as in Example 1, fecal Helicobacter pylori antigen measurement, blood pepsinogen (PGI and PGII) concentration, and blood anti-CagA antibody concentration were measured. Furthermore, for endoscopic verification, determination of endoscopic atrophy boundary by upper gastrointestinal tract examination (Kimura / Takemoto classification), intestinal metaplasia, histological gastritis evaluation (assessment by Sydney system; We examined the lower body and the upper body).

(1) Relationship between fecal H. pylori antigen OD value and gastritis distribution The method for determining gastritis distribution was performed according to the following criteria.
[Criteria]
No inflammation: According to Sydney classification, neutrophils of vestibule, vaginal, and vaginal neutrophils are normal Vestibular dominant gastritis: Level of neutrophils is vaccinated according to Sydney classification > Body Captain
pangastritis: The level of neutrophils in the Sydney classification is vestibule vaginalis = body vaginal corporal body gastritis: The level of neutrophils in Sydney classification is vestibule vats <body vault

  As shown in Table 9, when the fecal Helicobacter pylori antigen OD value was 1.5 or more, the average value of neutrophils in the large body of the stomach showed the highest value. In addition, in the distribution of gastritis, 46 out of 56 cases (82.2%) were determined to be pangastritis or body predominant gastritis when the fecal H. pylori antigen OD value was 1.5 or more. In addition, the fecal H. pylori antigen OD value showed significant positive correlation between the activity of large body corporal (neutrophil infiltration) and gastritis, and the fecal H. pylori antigen OD value was 1.5 or more. In this case, it was confirmed that the possibility of severe gastritis could be determined endoscopically. In addition, histologically active gastritis accompanied by neutrophil infiltration in the gastric body vaginalis known to be the least prone to inflammation in the gastric mucosa in populations with OD values> 2 or 1.5 (Pangastritis and body-dominated gastritis) were observed. In particular, there were many cases of pangastritis with advanced active gastritis in both the vestibule and stomach.

(2) Screening of PG method missed cases based on stool H. pylori antigen OD value As we proceeded with the examination of cases, the present inventors have determined that patients who have been judged negative by the PG method (PGI / PGII> 3 or PGI). > 70), there are severe gastritis patients, but even in cases where such PG method is missed, in the method of the present invention, by setting the standard of fecal H. pylori antigen OD value higher than 1.5, It has been found that by setting the standard of OD value to 2.0 typically, the gastritis state can be discriminated without missing.
That is, in the group negative for the PG method, the activity of corporal large bowel (neutrophil infiltration) was all OD <2 when it was mild, and the majority of cases where the OD value> 2 was moderate to high. In the pattern of gastritis, the OD value increased with pangastritis and body gastritis. On the other hand, such a tendency was not recognized in the PG method positive group.
Therefore, it was confirmed that if the OD value> 2, the neutrophil infiltration of the body part is high, and it is possible to determine that there is a high possibility of pangastritis or body part dominant gastritis. This also indicates that when the OD value> 2, it can be determined that this is a risk group for juvenile undifferentiated gastric cancer that is strongly related to the inflammation pattern of pangastritis and body-dominant gastritis.

(3) Examination of combined use of fecal H. pylori antigen OD value and PGI / PGII ratio As the H. pylori infection becomes chronic, the amount of H. pylori decreases. The initial population and the chronic population are mixed. Further, even in a population with an OD value ≧ 1.5, the transition level to gastric mucosa atrophy is mixed. Thus, precise determination may not be easy with only the OD value. In such a case, depending on the purpose to be determined, the PGI / PGII ratio can be used in combination in the method for determining the gastric mucosal state using the fecal H. pylori antigen OD value. In order to make it possible to determine the gastric mucosa state more effectively and precisely, the case where the reference value of the PGI / PGII ratio is set to 3 as in the PG method and the case where the reference value of the PGI / PGII ratio is set to 2 were examined. .

  The results in Table 10 and endoscopic verification of gastritis distribution suggested that populations with OD values <1.5 and PGI / PGII> 3 were H. pylori negative or early in infection. In addition, the population with an OD value <1.5 and PGI / PGII ≦ 2, the majority was body-dominated gastritis, and many cases with the most advanced chronicity were included.

In Table 11, the average value of the atrophy boundary indicates the average value with no atrophy, mild atrophy, moderate atrophy, and high atrophy as scores 1 to 4, respectively. Similarly, for the intestinal metaplasia, the average value of the four-stage scores was calculated.
From the results of Table 11, it was suggested that the population with an OD value <1.5 and PGI / PGII> 3 was H. pylori-negative or an early stage of infection even in the progress of atrophy (atrophy boundary) and intestinal metaplasia. . In addition, the population with an OD value <1.5 and PGI / PGII ≦ 2 had a high average value of intestinal metaplasia, and many cases with the most advanced chronicity were included.

  As shown in Table 12, the serum CagAIgG antibody and PGI / PGII against H. pylori suggested that the population with an OD value <1.5 and PGI / PGII> 3 was H. pylori negative or an early stage of infection. Compared with OD ≧ 1.5, populations with OD value <1.5 and PGI / PGII ≦ 2 have lower levels of antibodies against P. pylori, PGI and PGII, and the most chronic cases Many were included.

  As a diagnostic method for gastric mucosal inflammation, chronic gastritis (active gastritis, atrophic gastritis), risk of suffering from gastric cancer, or risk of suffering from the future, simple and efficient before performing diagnosis by endoscopy It is expected to be applied to software, computers, etc. used to analyze the health condition from test values in health examinations and the like.

Claims (5)

Quantitative measurement value (OD value) measured by enzyme immunoassay using an antibody against Helicobacter pylori antigen present in the stool of the subject,
A method for classifying the state of the gastric mucosa of the subject using as an index the ratio of the concentration of pepsinogen I to the concentration of pepsinogen II in the blood of the subject (PGI / PGII),
If the OD value exceeds 3 1.5 less than and PGI / PGII, risk factor for risk of or suffering from future suffering gastric cancer classified extremely low have state,
When the OD value is 1.5 or more and PGI / PGII exceeds 3,
When the OD value is 1.5 or more and PGI / PGII is 3 or less,
OD values are classified in the order hazard ratio suffering from gastric cancer or risk of suffering future is not high in the condition if less than 1.5 and PGI / PGII is 3 or less, said method. The condition of the subject's gastric mucosa,
If the OD value is less than 0.1 and PGI / PGII is greater than 3 , classify healthy,
When the OD value is 0.1 or more and less than 1.5 and PGI / PGII is greater than 3, the gastric mucosa is not accompanied by atrophy, and is classified into gastritis having mild inflammation,
If the OD value is 1.5 or more and PGI / PGII is greater than 3, it is classified as active gastritis with moderate to high inflammation without gastric mucosal atrophy,
When the OD value is 1.5 or more and PGI / PGII is 3 or less, it is classified as atrophic gastritis combined with highly active inflammation.
When the OD value is 0.1 or more and less than 1.5 and PGI / PGII is 3 or less, it is classified into the most progressive atrophic gastritis with mild to moderate inflammation.
The method of claim 1. The method according to claim 1, wherein when the OD value is 1.5 or more, the classification is made into a state of having a high risk of suffering from undifferentiated gastric cancer or a high risk of suffering from the future. 2. The method according to claim 1, wherein when the OD value is less than 1.5 and PGI / PGII is 3 or less, the method is classified into a state of having a high risk of suffering from differentiated gastric cancer or a high risk of suffering in the future.   The method according to any one of claims 1 to 4, wherein the antibody against Helicobacter pylori antigen is a monoclonal antibody.

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