JP6942030B2 - Anti-allergic agent susceptibility determination marker - Google Patents

Description

The present invention relates to a method for determining the susceptibility of a subject to an antiallergic agent containing lactic acid bacteria as an active ingredient. The present invention also relates to a susceptibility determination marker and a susceptibility determination kit used in the method.

In developed countries, the number of patients with allergic diseases such as pollinosis, perennial allergic rhinitis, and atopic dermatitis is increasing. In Japan as well, about one-third of people have had some allergic symptoms, and about 23.4% are said to have perennial allergic rhinitis. In patients with allergic diseases, in addition to allergic symptoms, symptoms such as headache, discomfort, insomnia, dissatisfaction, and anxiety may appear. These symptoms lower the patient's QOL and hinder work and study, which has become a major social problem (Non-Patent Documents 1 and 2). Anti-allergic drugs are taken to alleviate allergic symptoms, but anti-allergic drugs generally include antihistamines, steroids, immunosuppressants, etc., and there is concern about their side effects when taken for a long period of time.

Therefore, in recent years, there has been increasing interest in foods having an anti-allergic effect. It has been reported that some lactic acid bacteria and fruit juices have the effect of alleviating allergic symptoms. For example, fermented fruit juices produced by lactic acid bacteria such as Lactobacillus plantarum cause aggravation of symptoms and QOL disorders associated with the scattering of cedar pollen. It has been confirmed that it is alleviated (Non-Patent Documents 3 and 4 and Patent Document 1).

However, such anti-allergic agents may or may not have a palliative effect on allergic symptoms depending on the individual patient, and even if the effect is obtained, the degree of the effect varies. Foods that have an anti-allergic effect are effective when taken continuously on a daily basis. Therefore, if it is possible to distinguish between patients who can expect the effect (responder) and patients who cannot expect the effect (non-responder), It can reduce the burden on the patient and is useful in selecting a treatment method. Therefore, it is desired to develop a marker that can predict whether the effect of the antiallergic agent can be expected for each patient and a method for determining the marker.

Murota, H., Kitaba, S., Tani, M., Wataya-Kaneda, M., Azukizawa, H., Tanemura, A., Umegaki, N., Terao, M., Kotobuki, Y. and Katayama, I ., 2010. Impact of sedative and non-sedative antihistamines on the impaired productivity and quality of life in patients with pruritic skin diseases. Allergology International 59: 345-354. Neukirch, C., Liard, R., Bousquet, J. and Neukirch, F., 2000. Quality of life in allergic rhinitis and asthma. A population-based study of young adults. American Journal of Respiratory and Critical Care Medicine 162: 1391-1396. Harima-Mizusawa, N., Iino, T., Onodera-Masuoka, N., Kato-Nagaoka, N., Kiyoshima-Shibata, J., Gomi, A., Shibahara-Sone, H., Kano, M., Shida, K., Sakai, M., Miyazaki, K. and Ishikawa, F., 2014. Beneficial effects of citrus juice fermented with Lactobacillus plantarum YIT 0132 on Japanese Cedar Pollinosis. Bioscience of Microbiota, Food and Health 33: 147-155 .. Harima-Mizusawa, N., Kamachi, K., Kano, M., Nozaki, D., Uetake, T., Yokomizo, Y., Nagino, T., Tanaka, A., Miyazaki, K. and Nakamura, S ., 2016. Beneficial effects of citrus juice fermented with Lactobacillusplantarum YIT 0132 on atopic dermatitis: results of daily intake by adult patients in two open trials. Bioscience of Microbiota, Food and Health 35: 29-39.

International Publication No. 2011/115114

An object of the present invention is to provide an individual patient with a marker for predicting whether or not an effect of an antiallergic agent can be expected and a method for determining susceptibility to the antiallergic agent.

The present inventors have found a correlation between specific cells and their production substances and the degree of improvement in allergic symptoms in subjects who have ingested an antiallergic agent containing lactic acid bacteria, and by using this as a marker. We have found that the susceptibility to the antiallergic agent can be determined, and have completed the present invention.

That is, the present invention is an anti-lactic acid bacterium containing lactic acid bacteria as an active ingredient, which comprises one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic proteins (ECP). It is a susceptibility determination marker for allergens.

Further, the present invention is a method for determining the susceptibility of a subject to an antiallergic agent.
It includes a measurement step of measuring a biological substance in a biological sample of a subject, and a determination step of determining the susceptibility of the subject to an antiallergic agent based on the results obtained in the measurement step.
The anti-allergic agent contains lactic acid bacteria as an active ingredient,
The biological substance is one or more selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic proteins (ECP).
This is a method for determining the sensitivity of an antiallergic agent.

Furthermore, the present invention comprises a reagent for measuring one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic proteins (ECPs). It is a sensitivity determination kit for antiallergic agents contained as an active ingredient.

The present invention also makes effective lactic acid bacteria using parameters based on one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic proteins (ECP) as indicators. This is a method for screening an antiallergic agent containing an antiallergic agent as an ingredient.

According to the present invention, it is possible to determine the susceptibility of an individual patient to an antiallergic agent before administration, thereby reducing the burden on the patient and improving the therapeutic effect.

In the correlation analysis, it is a graph which plotted the sneezing symptom Δ value (questionnaire) with respect to the number of eosinophils of a test beverage group. In the correlation analysis, it is a graph which plotted the Symptom Score Δ value (questionnaire) with respect to the Th1 / Th2 ratio of the test beverage group. In the stratified analysis, the high and low Th2 cell ratio groups were stratified with a median of 0.80, and the sneezing symptom Δ value (questionnaire) and Symptom Scroe Δ value (questionnaire) were tested and placed in the test beverage (fermented juice) group and the placebo beverage group. It is a graph which made a comparison between groups with and. In the stratification analysis, the high and low Th1 / Th2 ratio groups were stratified with a median of 20.01, and the sneezing symptom Δ value (doctor interview) was compared between the test beverage (fermented juice) group and the placebo beverage group. It is a graph obtained by performing. In the stratified analysis, the high and low Th1 / Th2 ratio groups were stratified with a median value of 20.01, and the sneezing symptom Δ value (questionnaire) and Symptom Scroe Δ value (questionnaire) were tested and placed in the test beverage (fermented juice) group and the placebo beverage. It is the graph which performed the comparison between the group and the group. In the stratified analysis, the high and low eosinophil count groups were stratified with a median of 190, and the sneezing symptom Δ value (questionnaire) was compared between the test beverage (fermented juice) group and the placebo beverage group. It is a graph that was done. In the stratified analysis, the high and low ECP concentration groups were stratified with a median value of 5.7, and the test beverage (fermented juice) group and placebo beverage group were used for the squeezing symptom Δ value (questionnaire) and the total itching Δ value (questionnaire). It is a graph which made a comparison between groups with and.

The susceptibility determination marker for the antiallergic agent of the present invention is one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP).

Treg cells (regulatory T cells) are a subset of T cells that play a role in suppressing the immune response, maintaining immune tolerance and the homeostasis of the immune system, and suppress the excessive immune response in order to suppress the allergic reaction. Stimulates the induction of cytokines.

CD4-positive T cells are divided into Th1 cells and Th2 cells according to the cytokine production pattern. Th1 cells produce IL-2, IFN-γ, TGF-β, etc. and are involved in the response of cell-mediated immunity, and Th2 cells are IL-4, IL-5, IL-6, IL-10, IL-13. And are involved in the induction of humoral immunity.

Eosinophils are a type of granulocytes and have large, acidophilic granules. Production increases due to tissue inflammation and immune response caused by parasitic infections and allergic diseases. Eosinophil Cationic Protein (ECP) is one of the eosinophil granule proteins and is released from activated eosinophils.

In the present invention, the antiallergic agent to be determined for susceptibility contains lactic acid bacteria as an active ingredient. The lactic acid bacterium is not particularly limited as long as it has anti-allergic activity, and lactic acid bacteria such as Lactobacillus, Streptococcus, Lactococcus, Leuconostoc, Enterococcus, Pediococcus, and Bifidobacterium can be used. Can be used. Specifically, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus casei, Lactobacillus del Brucchii, Lactobacillus fermentum, Lactobacillus herveticas, Lactobacillus kefia, Lactobacillus paracasei, Lactobacillus Lactobacillus ramnosus, Lactobacillus salivalius, Lactobacillus pentosas, Lactobacillus salmon, Streptococcus thermophilus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus raffinolactis, Leukonostock Lactis, Leukonostock Mecenteroides, Bifidobacterium Breve, Bifidobacterium Longum, Bifidobacterium Bifidum, Bifidobacterium Animalis, Bifidobacterium Zuis, Bifidobacterium Infan Tiss, Bifidobacterium addressntis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenuratum, Bifidobacterium lactis, Bifidobacterium globosam, etc., and one of them or Two or more types can be used. Among these, lactic acid bacteria belonging to the genus Lactobacillus are preferable, and Lactobacillus plantarum is particularly preferable, specifically, Lactobacillus plantarum YIT 0132 (FERM BP-11349) and Lactobacillus plantarum YIT 0148 (FERM). BP-11350) and the like. The antiallergic agent in the present invention may contain cells of these lactic acid bacteria, and the cells may be dead cells or live bacteria. The form may be any form that can be ingested orally, and includes pharmaceuticals, foods and drinks, and the like. The content of lactic acid bacteria contained in the antiallergic agent is also not particularly limited, but in the case of beverages, for example, the cell concentration of lactic acid bacteria ^{may be about 1 × 10 4} to 1 × 10 ⁸ CFU / 100 ml.

Allergic diseases to be treated / prevented by antiallergic agents include, for example, atopic dermatitis, food allergies, allergic asthma, perennial allergic rhinitis, seasonal allergic rhinitis such as pollinosis, and allergic conjunctivitis. Examples include urticaria, and among these, it is preferably used for patients with perennial allergic rhinitis, seasonal allergic rhinitis, and the like. Allergic symptoms based on these diseases include asthma, sneezing, runny nose, nasal congestion, itching of nose, eyes, skin, eczema, skin abnormalities, bronchial abnormalities, etc. Among these, sneezing, runny nose, etc. It is suitably used for determining nasal symptoms such as nasal congestion and improvement of symptoms such as sneezing.

The method for determining susceptibility to an antiallergic agent of the present invention uses parameters based on biological substances such as Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP), which are the susceptibility determination markers. First, in the measurement step, these biological substances contained in the biological sample of the subject are analyzed and measured. Examples of biological samples include blood, serum, plasma, lymph, nasal lavage fluid, and skin tissue samples.

The analysis / measurement of the biological substance can be carried out according to a conventional method. For example, among biological substances, cells such as Treg cells, Th1 cells, Th2 cells, and eosinophils can be analyzed by flow cytometry and identified using antibodies against a subset characteristic of each cell. Th1 cells and Th2 cells can be detected and quantified by a flow cytometer by stimulating lymphocytes in a state of suppressing extracellular secretion to promote cytokine production and reacting with anti-cytokine antibody. The parameters based on these biological substances are not particularly limited, and include the number, concentration, ratio, etc. of each biological substance. Specifically, Th1 cell ratio, Th2 cell ratio, Th1 / Th2 ratio, Treg cell ratio, etc. , The number of eosinophils and the like are exemplified. The Th1 cell ratio is the ratio (%) of the number of Th1 cells (IFN-γ positive, IL-4 negative) to the number of helper T cells (CD4 positive T cells), and the Th2 cell ratio is the helper T cells (CD4 positive T cells). It is calculated as the ratio (%) of the number of Th2 cells (IFN-γ negative, IL-4 positive) to the number. The Th1 / Th2 ratio is calculated as the number of Th1 cells / the number of Th2 cells (%). The Treg cell ratio is determined as the ratio of the number of Treg cells (CD4 positive, CD25 positive, Foxp3 positive) to the number of helper T cells (CD4 positive T cells). The serum concentration (μg / L) of eosinophil basic protein (ECP) can be measured by an enzyme-linked immunosorbent assay (ELISA) method, a radioimmunoassay (RIA) method, an immunochromatography method, a fluorescent bead microarray method, or the like.

When the Treg cell ratio, Th2 cell ratio, eosinophil count or eosinophil basic protein (ECP) concentration are used as parameters based on the biological substance in the method of the present invention, these values are measured in the measuring step. However, when the value is higher than a predetermined threshold value, it can be determined that the subject is in the hypersensitive group to the antiallergic agent in the determination step. On the other hand, when these values are lower than the threshold value, it can be determined that the subject is in the hyposensitive group to the antiallergic agent in the determination step.

When the Th1 cell ratio or Th1 / Th2 ratio is used as a parameter based on a biological substance, when these values measured in the measurement step are lower than a predetermined threshold, the subject is higher than the antiallergic agent in the determination step. It can be determined that it is a sensitive group. On the other hand, when these values are higher than a predetermined threshold value, it can be determined that the subject is in the hyposensitive group to the antiallergic agent in the determination step. A predetermined threshold value as a reference is not particularly limited, and can be set empirically by accumulating data on various biological samples. As the threshold value, as shown in the examples below, the median value of the initial values of the blood parameters of a plurality of subjects can be used, the threshold value of the Th2 cell ratio is 0.80, the threshold value of the Th1 / Th2 ratio is 20.01, and the number of eosinophils. 190 can be exemplified as the threshold value of, and 5.7 as the threshold value of ECP concentration, but the present invention is not limited thereto.

In the present invention, from the viewpoint of improving the determination accuracy, Treg cell ratio, Th2 cell ratio, eosinophil basic protein (ECP) concentration, Th1 / Th2 ratio, and eosinophil count can be used as parameters based on the biological substance. preferable. Furthermore, since the determination accuracy is further improved, it is preferable to use two or more types of parameters based on biological substances in combination, and since the determination accuracy is significantly improved, the Treg cell ratio and the number of eosinophils are one of the combined parameters. Alternatively, it is preferable to use the ECP concentration, and the eosinophil count or the ECP concentration particularly improves the accuracy for improving the nasal discharge symptom, and the Treg cell ratio particularly improves the accuracy for improving the nasal congestion symptom. Among such combinations, the combination of the Treg cell ratio and the eosinophil count improves the accuracy for improving nasal discharge symptoms, and the combination of the Treg cell ratio and the ECP concentration improves the judgment accuracy for a wide range of symptoms. Here, the improvement of the determination accuracy means that the p value becomes smaller in the result of the significant difference test (Wilcoxon rank sum test) between the high-sensitivity group and the low-sensitivity group. ..

As described above, before ingestion of the antiallergic agent, the value of the parameter based on the biological substance can be measured in advance from the biological sample of the subject, and the sensitivity of the subject to the antiallergic agent can be determined. Therefore, it is possible to reduce the burden on patients who require continuous intake for a long period of time and optimize the therapeutic effect.

The present invention includes a kit for performing the above-mentioned susceptibility determination method. The kit contains reagents for detecting and quantifying biological substances that are susceptibility determination markers, such as a subset of T cells to be measured, an antibody against cytokines or ECPs, and the like.

Further, in the present invention, a lactic acid bacterium is used as an index based on a parameter based on one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP). A method for screening an antiallergic agent-enhancing agent contained as an active ingredient is included. As parameters based on biological substances, substances that increase the Treg cell ratio, Th2 cell ratio, eosinophil count, and eosinophil basic protein (ECP) concentration are substances that enhance sensitivity. On the other hand, substances that lower the Th1 cell ratio and Th1 / Th2 ratio are substances that increase sensitivity. Using these parameters as indicators, substances that can increase the sensitivity to antiallergic agents can be screened.

Hereinafter, the present invention will be described in detail by way of examples, but the present invention is not limited to these examples.

Example 1
For patients with perennial allergic rhinitis who are undergoing outpatient treatment, double-blind drinks prepared by the following method using Lactobacillus plantarum YIT 0132 (FERM BP-11349) for 8 consecutive weeks. A placebo-controlled parallel-group comparative study was conducted (16 in the test beverage group and 16 in the placebo beverage group). Each subject was asked to record subjective symptoms every day for one week before drinking and during the drinking period according to the following evaluation method, and a Symptom score (comprehensive evaluation of rhinitis symptoms) was calculated based on the results. In addition, before drinking and 8 weeks after drinking, nasal symptoms were evaluated and blood parameters were measured by interviewing a doctor according to the following method. Correlation analysis was performed between each symptom Δ value (post-drink symptom score-pre-drink symptom score) of the test drinking group and the blood parameter (initial value) before drinking, and the blood parameter correlating with the Δ value of each symptom score was extracted. Next, based on the median of all subjects with the initial values of the extracted blood parameters, they were stratified into a low value group and a high value group, and each symptom score Δ value was compared within the test beverage group and the test beverage group and the placebo beverage. Group-to-group comparisons were made.

(Preparation of test beverage)
Wenshu mandarin juice (manufactured by Nankai Fruit Factory) is inoculated with Lactobacillus plantarum YIT0132 bacterial solution that has been cultivated until it reaches a steady state, and after culturing at 37 ° C for 48 hours, it is sterilized by heating at 90 ° C for 5 minutes to prepare the test beverage. Prepared. The placebo beverage was prepared using unfermented Satsuma mandarin juice so as to be indistinguishable from the test beverage in terms of flavor and appearance. The number of cells of Lactobacillus plantarum YIT0132 in the test beverage was 6 × 10 ¹⁰ cells / 100 ml by the DAPI measurement method.

(Evaluation of symptoms)
[Subjective symptoms (questionnaire)]
According to the guidelines (Okuda, M., 2005. Allergic rhinitis. Iyaku Journal Company Limited, Osaka, Japan. Okuda, M., 2010. Japanese guideline for the diagnosis and treatment of allergic diseases. Kyowa Kikaku Company Limited, Tokyo, Japan. 2010) , Squeezing, nasal juice, and nasal obstruction were scored on a scale of 0 to 4 as a nasal symptom score. In addition, itching of the nose, itching of the eyes, and itching of the skin were also scored in the same manner. Table 1 shows the scoring method for each symptom. The Sympton Score (comprehensive evaluation of rhinitis symptoms) was calculated according to the "Nasal Allergy Practice Guidelines 2009 Edition". The total itchiness was determined by the total score of nasal itchiness, eye itchiness, and skin itchiness. The average value of the pre-drinking period (1 week) was defined as the pre-drinking symptom score, and the average value of 5 to 8 weeks out of the 8-week drinking period was defined as the post-drinking symptom score.

[Doctor interview]
Before and 8 weeks after drinking, the four items of sneezing, runny nose, nasal congestion, and severity were evaluated and scored by a doctor on a scale of 0 to 4, and were used as the pre-drinking symptom score and the post-drinking symptom score, respectively.

(Measurement of blood parameters)
Blood samples were taken from the brachial blood vessels of the subject before drinking (initial value) and 8 weeks after drinking. Serum was prepared according to a conventional method. Total serum IgE and eosinophil basic protein (ECP) were measured by fluorescent enzyme immunoassay. The eosinophil count, Th1 cell ratio, Th2 cell ratio, Treg ratio, and Th1 / Th2 ratio were measured by flow cytometry (Sysmex XE-2100, manufactured by Sysmex Corporation). The Th1 cell ratio is the ratio of the number of Th1 cells (IFN-γ positive, IL-4 negative) to the number of helper T cells (CD4 positive T cells), and the Th2 cell ratio is the ratio of Th2 cells (IFN-γ positive, IL-4 negative) to the number of helper T cells (CD4 positive T cells). IFN-γ negative, IL-4 positive) number ratio, Th1 / Th2 ratio is the ratio of Th1 cell number to Th2 cell number, Treg cell ratio is Treg cell (CD4 positive, CD4 positive,) number of helper T cells (CD4 positive T cells) It was calculated as the ratio of the number of CD25 positive and Foxp3 positive).

As a result of correlation analysis, Treg cell ratio, Th2 cell ratio, eosinophil count, and ECP concentration were extracted as blood parameters showing a negative correlation (Spearman's rank correlation coefficient r <-0.4) with the Δ value of each symptom score. Was done. In addition, Th1 / Th2 ratio and Th1 cell ratio were extracted as blood parameters showing a positive correlation (r> 0.4) (see FIGS. 1 and 2). From the relationship between the correlation coefficient (negative and positive) and the Δ value of the symptom score, the blood parameter showing a negative correlation is a high-valued person, and the blood parameter showing a positive correlation is a low-valued person.・ Plantalum YIT1032 Judged as a responder to fermented fruit juice. Those having a p-value of 0.1 or less were extracted as "correlated blood parameters". On the other hand, total serum IgE has been suggested to be involved in the development of perennial allergic rhinitis symptoms, but no correlation was found in susceptibility.

From the results of stratification analysis (comparison within the group), the Treg cell ratio, Th2 cell ratio, eosinophil count, and ECP concentration high initial value group were significant compared to the initial low value group (p <0.05; Wilcoxon ranking). The sum test) showed improvement or improvement tendency (p <0.1). In addition, the low initial value group of Th1 / Th2 ratio and Th1 cell ratio was significantly improved or tended to improve as compared with the high initial value group.

From the results of stratified analysis (comparison between groups), in the group with high initial values of Th2 cell ratio and eosinophil count, squeezing symptoms in the test beverage group (fermented juice group) compared with the placebo beverage group (placebo group). Was significantly improved (p <0.05; Wilcoxon rank sum test). In addition, the Symptom score (comprehensive evaluation of rhinitis symptoms) was improved in the group with the high initial value of Th2 cell ratio, and the total of sneezing and itching was improving (p <0.1) in the group with the high initial value of ECP concentration. On the other hand, in the low initial value group of Th1 / Th2 ratio, the sneezing symptom and the Symptom score were significantly improved in the test beverage group, and the sneezing symptom of the doctor's interview showed an improving tendency (see FIGS. 3 to 7).

The pre-drinking symptom score of each symptom is the same in the initial value low value group and the initial value high value group of each blood parameter of the test beverage group, and the initial value low value group and the initial value of each blood parameter of the placebo beverage group. It was similar in the high price group. That is, it was confirmed that each of these blood parameters is generally suggested to be involved in the onset of allergic symptoms, but is not directly correlated with the severity (initial value) of allergic symptoms of the subject. .. Therefore, the results of this analysis are based on the new finding that susceptibility to antiallergic agents can be determined with high accuracy only by comparing the initial values of each blood parameter with a predetermined threshold value regardless of the severity of allergic symptoms. It is a thing.

Furthermore, it was examined whether the responder detection accuracy could be improved by combining blood parameters. The Willcoxon test was performed on the nasal discharge symptom score Δ in the high eosinophilia group and the other groups (Table 2). On the other hand, the Willcoxon test was performed in the same manner in the group in which both the eosinophil count and the Treg cell ratio were high and in the other groups (Table 3).

From this result, it was shown that the determination accuracy was improved by combining the eosinophil count and the Treg cell ratio rather than the eosinophil count alone.

The Willcoxon test was performed for the nasal discharge symptom score Δ in the high ECP concentration group and the other groups (Table 4). On the other hand, the Willcoxon test was performed in the same manner in the group in which both the Treg cell ratio and the ECP concentration were high and in the other groups (Table 5).

From this result, it was shown that the judgment accuracy was improved by combining the Treg cell ratio and the ECP concentration rather than the ECP concentration alone.

The Willcoxon test was performed for the nasal congestion symptom score Δ in the high Treg cell ratio group and the other groups (Table 6). On the other hand, the Willcoxon test was performed in the same manner in the group in which both the Treg cell ratio and the ECP concentration were high and in the other groups (Table 7).

From this result, it was shown that the judgment accuracy was improved by combining the Treg cell ratio and the ECP concentration rather than the Treg cell ratio alone.

INDUSTRIAL APPLICABILITY The present invention can be used as a method for determining whether or not an antiallergic agent containing lactic acid bacteria as an active ingredient can be expected to have an allergic symptom-relieving effect before ingestion.

Claims (10)

About anti-allergic agents containing lactic acid bacteria as an active ingredient
Measure one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP) in the blood of the subject collected before ingestion of anti-allergy. However, when the Treg cell ratio, Th2 cell ratio, eosinophil count or eosinophil basic protein (ECP) concentration is higher than a predetermined threshold, or the Th1 cell ratio or the ratio of Th1 cell number to Th2 cell number (Th1). / Th2) is lower than a predetermined threshold, and the purpose is to determine the susceptibility to antiallergic agents by determining that the subject is in the hypersensitive group to antiallergic agents, before ingestion of antiallergic agents. A method for measuring one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP) from the blood of a subject collected in. Lactic acid bacteria, a method for measuring biological material according to claim 1 wherein the lactic acid bacteria of the genus Lactobacillus. Lactic acid bacteria, a method for measuring biological material according to claim 1 wherein the Lactobacillus plantarum. The method for measuring a biological substance according to any one of claims 1 to 3 , wherein the biological sample is blood. Subject ingests antiallergic agent, containing a reagent for measuring one or more biological substances selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP). It is a susceptibility determination kit for antiallergic agents containing lactic acid bacteria as an active ingredient, which measures the amount of biological substances from blood collected before the preparation, and the biological substances are Treg cells, Th2 cells, eosinophils or eosinophil basics. In the case of protein (ECP), if the measured amount of biomaterial is higher than a predetermined threshold, it is judged to be highly sensitive to antiallergic agents, and if the biomaterial is Th1 cells, the measured biomaterial. A susceptibility determination kit for an antiallergic agent containing lactic acid bacteria as an active ingredient, which is determined to be highly sensitive to an antiallergic agent when the amount of The susceptibility determination kit according to claim 5 , wherein the lactic acid bacterium is a lactic acid bacterium belonging to the genus Lactobacillus. The susceptibility determination kit according to claim 5 , wherein the lactic acid bacterium is Lactobacillus plantarum. One or more biological material selected from the group consisting of Treg cells, Th1 cells, Th2 cells, eosinophils and eosinophil basic protein (ECP) measured from blood collected before the subject ingested the antiallergic agent. The biomaterial-based parameters are Treg cell ratio, Th1 cell ratio, Th2 cell ratio, Th1 / Th2 ratio, eosinophil count or eosinophil basic protein (ECP) concentration. If the substance-based parameters are Treg cell ratio, Th2 cell ratio, eosinophil count or eosinophil basic protein (ECP) concentration, select a substance that increases the biomaterial-based parameter, and the biomaterial-based parameter is A method for screening an antiallergic agent containing lactic acid bacteria as an active ingredient, which selects a substance that lowers a parameter based on a biological substance in the case of a Th1 cell ratio or a Th1 / Th2 ratio. The screening method according to claim 8 , wherein the lactic acid bacterium is a lactic acid bacterium belonging to the genus Lactobacillus. The screening method according to claim 8 , wherein the lactic acid bacterium is Lactobacillus plantarum.

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