CN113155996A - Use of 15(S) -hydroxyeicosatetraenoic acid for evaluating allergen specific immunotherapy efficacy - Google Patents
Use of 15(S) -hydroxyeicosatetraenoic acid for evaluating allergen specific immunotherapy efficacy Download PDFInfo
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Abstract
The present invention provides the use of 15(S) -hydroxyeicosatetraenoic acid in the assessment of the efficacy of allergen specific immunotherapy. The 15(S) -hydroxyeicosatetraenoic acid can be used as a serological marker in the construction of a kit or an evaluation method. According to the invention, non-target metabonomics analysis and target metabonomics analysis are carried out on different serum samples including serum samples of allergic asthma patients, healthy human bodies and allergic asthma patients receiving allergen specific immunotherapy, so that the content of 15(S) -hydroxyeicosatetraenoic acid in the allergic asthma patients and the healthy human bodies is remarkably different, and the 15(S) -hydroxyeicosatetraenoic acid is an objective, specific and highly sensitive serological marker capable of reflecting the treatment effect of the allergen specific immunotherapy.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a serological marker for evaluating allergen specific immunotherapy effect.
Background
Metabolomics (metabolomics) is an important subject for qualitative and quantitative analysis of metabolites. Biological information in an organism is transferred to protein through transcription of genes and finally embodied as small molecule metabolites, wherein the small molecule metabolites not only are the material basis of life activities and biochemical metabolism of the organism, but also embody the change of certain external factors to the metabolism environment in the organism, so that the difference of the concentration of certain unique metabolites among different individuals actually reflects the internal manifestation and external cause of diseases.
In recent years, metabonomics provides a novel technical method for screening and early diagnosis of complex chronic diseases, and is widely used for searching biomarkers of complex chronic diseases, researching pathogenic pathways of diseases and the like. Metabonomics qualitatively and quantitatively detect all small molecule metabolites with the molecular weight lower than 1000Da in a sample, such as fatty acid, amino acid, nucleoside, steroid and the like, so as to monitor metabolic response in an organism and judge whether the small molecule metabolites are interfered by disease or dangerous factor accumulation and the like according to the content of the small molecule metabolites. Unlike the intra-organism differences reflected by genomics and proteomics, the field of metabolomics research extends to the interplay and interaction between the organism and the environment.
In metabonomic analysis, qualitative and quantitative analysis is mainly performed on metabolites, and the detection means mainly comprises the mainstream technologies in the chemical analysis field, such as Nuclear Magnetic Resonance (NMR), Mass Spectrum (MS), High Performance Liquid Chromatography (HPLC), Ultra High Performance Liquid Chromatography (UHPLC) and the like. The mass spectrometry detection technology has higher detection sensitivity, and can perform chromatographic separation and mass spectrometry detection on metabolites in a complex sample after being combined with the chromatographic technology, so that the interference of a matrix is reduced, and the detection of trace metabolites is facilitated.
Allergic asthma (Allergic asthma) is a common Allergic disease characterized by airway inflammation (Allergic diseases). Allergic asthma is often recurrent, requiring long-term administration of steroids and antihistamines to control symptoms; however, these drugs are liable to cause various side effects such as skin atrophy, osteoporosis, fatty liver disease and type II diabetes syndrome, and growth inhibition in children, and thus the range of use of the drugs is limited.
Allergen specific immunotherapy (AIT) is a treatment that can alter the course of allergic diseases. Although the European Association of Allergy and Clinical Immunology (EAACI) currently proposes various immunological criteria (e.g., allergen-specific IgG4 concentration, specific IgE to total IgE concentration ratio, etc.) to assess the efficacy of AIT. However, there is still a lack of objective, highly sensitive and specific biomarkers for assessing or monitoring the efficacy of clinical patients after receiving AIT.
Therefore, the selection of a suitable biomarker to evaluate the effect of allergen-specific immunotherapy is of great significance for expanding the application range of allergen-specific immunotherapy.
Disclosure of Invention
In view of the problems of the prior art, the present invention aims to provide the use of 15(S) -hydroxyeicosatetraenoic acid for evaluating the effect of allergen-specific immunotherapy. Metabonomic analysis of serum from allergic asthma patients, healthy persons and patients with allergic asthma who received AIT confirmed that 15(S) -hydroxyeicosatetraenoic acid was able to objectively, specifically and highly sensitively reflect the therapeutic effects of AIT.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides the use of 15(S) -hydroxyeicosatetraenoic acid (15(S) -hydroxyeicosanoic acid, 15(S) -HETE) as a serological marker in the preparation of a kit for evaluating the effect of allergen-specific immunotherapy or in the construction of a method for evaluating the effect of allergen-specific immunotherapy.
The structural formula of the 15(S) -hydroxyeicosatetraenoic acid is shown as the formula (I):
in the present invention, the content of the serological marker 15(S) -HETE in allergic asthma patients and healthy persons is significantly different, FC (asthma/normal) is 2.39 and AUC is 0.89(P is 0.0028),
And monitoring the serum content of 15(S) -HETE in patients receiving allergen-specific immunotherapy treatment for three years reveals that the metabolite increases in the first year of allergen-specific immunotherapy treatment and then decreases from the first year to the third year, significantly below the baseline level after three years of treatment, and therefore, the use of 15(S) -HETE can be used to assess the therapeutic efficacy of allergen-specific immunotherapy.
As a preferred embodiment of the present invention, the kit for evaluating the effect of allergen-specific immunotherapy comprises: a reagent for detecting the content of 15(S) -hydroxyeicosatetraenoic acid.
Preferably, the kit for evaluating the effect of allergen-specific immunotherapy further comprises other reagents for detecting the content of serological markers, for example, for detecting 5(S) -hydroxyeicosatetraenoic acid (5(S) -HETE), 8(S) -hydroxyeicosatetraenoic acid (8(S) -HETE), 11(S) -hydroxyeicosatetraenoic acid (11(S) -HETE), 12(S) -hydroxyeicosatetraenoic acid (12(S) -HETE), 5(S) -hydroxyeicosatetraenoic acid (5(S) -hydroxyeicosatetraenoic acid, 5(S) -HPETE), 12(S) -hydroxyeicosatetraenoic acid (12(S) -HPETE), 15(S) -hydroxyeicosatetraenoic acid (15(S) -HPETE) or Arachidonic acid (Arachidonic acid), AA) or at least two serological marker levels.
In the invention, by analyzing eicosanoid metabolites of serum samples, a plurality of different metabolites including 15(S) -HETE are found, and the metabolites can reflect the health level of patients and the treatment effect of treatment modes. If 15(S) -HETE is combined with other metabolites and the content of each substance in the combination is detected, the health condition in the sample can be more accurately evaluated and judged.
As a preferred embodiment of the present invention, the kit for evaluating the effect of allergen-specific immunotherapy comprises: reagents for measuring the content of 15(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid and 12(S) -hydroxyeicosatetraenoic acid.
In the invention, the 15(S) -HETE is a product obtained by 15(S) -HPETE under the action of Glutathione peroxidase (GPx). Therefore, the 15(S) -HPETE, the 15(S) -HETE and the 12(S) -HETE are simultaneously used as detection targets, so that the accuracy of the evaluation result can be further improved.
In the present invention, the 15(S) -HETE capable of being used as a serological marker for evaluating the allergen-specific immunotherapy effect is obtained by screening according to the following method, and the specific steps are shown in fig. 1, and include:
s1, collecting serum samples of healthy children and asthmatic children and preprocessing the serum samples
(1) Collecting a serum sample, adding ethyl acetate into the serum sample, wherein the volume ratio of the serum sample to the ethyl acetate is 1 (2-5), centrifuging, collecting a supernatant, and drying under a nitrogen flow;
(2) and then mixing the pretreated serum sample, HOBt (1-hydroxybenzotriazole), HATU (2- (7-azabenzotriazole) -N, N, N ', N' -tetramethyluronium hexafluorophosphate) and (2-aminoethyl) trimethylammonium chloride hydrochloride, and reacting to obtain a derivative sample.
Wherein the derivatization can be represented by formula (II):
wherein R represents an arbitrary hydrocarbon group and TEA represents a reaction buffer, and the reaction can be carried out at room temperature.
The derivatization method and the method of the combination of chromatographic mass spectrometry described in the present invention are described in Bian X, Sun B, Zheng P, et al, differentiation enhanced separation and sensitivity of a long chain-free defect acid, Application to assay target and non-target liquid chromatography-mass spectrometry approach [ J ]. analytical Chimica Acta,2017:59.
S2, derivatization UHPLC-Q-TOF/MS analysis: analyzing the obtained normal serum sample and the serum sample of the allergic diseases by adopting derivatization-UHPLC-Q-TOF/MS (Ultra-high performance liquid chromatography-quadruple-time of flight/MS);
s3, non-targeted metabolomics analysis: combining the analysis result of derivatization-UHPLC-Q-TOF/MS with non-target metabonomics analysis and target metabonomics analysis;
s4, potential biomarker: screening candidate potential biomarkers;
s5, collecting serum samples of children receiving specific immunotherapy and preprocessing: collecting serum samples of children receiving specific immunotherapy by the same method, including serum samples at 0 year, 0.5 year, 1 year, 2 years and 3 years of treatment;
s6, derivatization UHPLC-QQQ-MS analysis: the serum sample receiving allergen specific immunotherapy is analyzed by derivatization-UHPLC-QQQ-MS;
s7, eicosanoid-target metabolome analysis: performing eicosanoid-target metabonomics analysis on the obtained analysis result;
s8, metabolite differences: combining the candidate potential biomarkers to obtain serological markers for predicting allergen-specific immunotherapy effect;
s9, GPx-HETEs: metabolic pathways of eicosanoids were analyzed.
As a preferred embodiment of the present invention, the method for evaluating the effect of allergen-specific immunotherapy comprises: the amount of 15(S) -hydroxyeicosatetraenoic acid in the serum sample is measured and the effect of allergen-specific immunotherapy is evaluated on the basis of the amount.
Preferably, the method of assessing the effect of allergen-specific immunotherapy further comprises:
detecting the amount of any one or at least two serological markers of 5(S) -hydroxyeicosatetraenoic acid, 8(S) -hydroxyeicosatetraenoic acid, 11(S) -hydroxyeicosatetraenoic acid, 12(S) -hydroxyeicosatetraenoic acid, 5(S) -hydroxyeicosatetraenoic acid, 12(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid or arachidonic acid in a serum sample, and assessing the effect of allergen-specific immunotherapy based on the amount of each said serological marker.
In the method for evaluating the effect of allergen-specific immunotherapy, the method for detecting the content of the serological marker comprises the following steps: derivatized UHPLC-Q-TOF/MS analysis.
Preferably, the method of assessing the effect of allergen-specific immunotherapy wherein the serum sample is pre-treated comprises: and adding ethyl acetate into the serum sample, wherein the volume ratio of the serum sample to the ethyl acetate is 1 (2-5), centrifuging, collecting the supernatant, and drying under a nitrogen flow.
Preferably, the derivatization method is: and mixing the serum sample obtained after the pretreatment, HOBt, HATU and (2-aminoethyl) trimethyl ammonium chloride hydrochloride for reaction.
In a third aspect, the present invention also provides the use of a combination of 15(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid and 12(S) -hydroxyeicosatetraenoic acid as serological markers for the preparation of a kit for evaluating the effect of an allergen-specific immunotherapy or for the construction of a method for evaluating the effect of an allergen-specific immunotherapy.
Compared with the prior art, the invention has at least the following beneficial effects:
the invention is subjected to derivatization-UHPLC-Q-TOF/MS analysis and metabonomics analysis, carrying out differential analysis on serum metabolites of healthy children and house dust mite allergic asthma children, screening out potential 9 biomarkers, also, attention was paid to the changes in eicosanoid metabolites in allergic asthmatic children during three years of subcutaneous immunotherapy (SCIT), and analyzing by adopting derivatization-UHPLC-QQQ-MS, selecting (2-aminoethyl) trimethyl ammonium chloride hydrochloride as a derivatization reagent, improving the sensitivity and separation efficiency of UHPLC-Q-TOF/MS for analyzing carboxylic acid, and obtaining that 15(S) -hydroxyeicosatetraenoic acid in children in an asthma group is obviously higher than that in children in a health group, FC (asthma/normal) is 2.39, and the obtained product has a good AUC value, and the AUC is 0.89(P is 0.0028); furthermore, this metabolite increases in the first year of SCIT treatment and then decreases from the first year to the third year, significantly below baseline levels after three years of treatment, and therefore 15(S) -hydroxyeicosatetraenoic acid can be used as a serological marker to assess the effect of allergen-specific immunotherapy.
Drawings
FIG. 1 is a schematic flow chart of the screening method of the serological marker of the present invention.
FIG. 2A is a graph showing the results of PCA analysis of the allergic asthma patients and healthy control groups in example 1.
FIG. 2B is a graph of OPLS-DA scores of the allergic asthma patients and healthy controls of example 1.
FIG. 2C is a graph of the stress S-point for the allergic asthma patient of example 1 versus a healthy control.
FIG. 3A is a graph of the distribution of asthma metabolite levels in allergic asthma patients in example 2.
FIG. 3B is a heat map of different eicosane compounds from example 2.
FIG. 3C is a graph comparing the change in eicosane compound levels between healthy individuals and patients with allergic asthma in example 2, in which graphs a to i show the contents of AA, 5(S) -HPETE, 12(S) -HPETE, 15(S) -HPETE, 5(S) -HETE, 8(S) -HETE, 11(S) -HETE, 12(S) -HETE and 15(S) -HETE, respectively.
Fig. 3D is a graph of the pathway enrichment results for the candidate biomarkers in example 2.
Figure 3E is the predicted Variable Importance (VIP) scores for the 8 metabolites in example 2.
FIG. 4A is a graph showing the dynamic changes of 12(S) -HPETEs and 12(S) -HETEs in serum during SCIT in example 3; wherein (I) is 12(S) -HPETEs, and (II) is 12(S) -HETEs.
FIG. 4B is a graph showing the dynamic changes of 15(S) -HPETEs and 15(S) -HETEs in serum during SCIT in example 3; wherein (I) is 15(S) -HPETEs, and (II) is 15(S) -HETEs.
FIG. 4C is a graph showing the dynamic changes of 5(S) -HPETEs and 5(S) -HETEs in serum during SCIT in example 3; wherein (I) is 5(S) -HPETEs, and (II) is 5(S) -HETEs.
FIG. 4D is a graph showing the dynamic changes of 8(S) -HETES and 11(S) -HETES in serum during SCIT in example 3; wherein (I) is 8(S) -HETEs, and (II) is 11(S) -HETEs.
FIG. 5A is a graph showing the absolute concentration of 12(S) -HETES in serum samples obtained during SCID of the allergic asthma patient in example 3.
FIG. 5B is a schematic representation of the metabolic pathway of the eicosanoid compound of example 3.
Detailed Description
The technical solutions of the present invention are further described in the following embodiments with reference to the drawings, but the following examples are only simple examples of the present invention and do not represent or limit the scope of the present invention, which is defined by the claims.
In the following examples, unless otherwise specified, reagents and consumables were purchased from conventional reagent manufacturers in the field; unless otherwise indicated, all experimental methods and technical means used are those conventional in the art.
All experiments in this invention were approved by the ethical committee of the first subsidiary hospital of Guangzhou medical university.
Example 1
The present example is used for screening the serological markers of allergic asthma, and specifically includes the following steps:
study subjects: baseline demographic data and related information including gender, age, BMI, clinical symptoms, skin prick tests, initial diagnosis, familiar disease, household characteristics, treatment methods, etc. were collected for study participants at the time of sample collection.
In this example, 50 children were used as subjects, and 35 patients with allergic asthma passed the inclusion and exclusion criteria, including 20 patients receiving house dust mite (Dermatophagoides pteronyssinus, Derp) SCIT (Alutard ALK-Abello,
denmark) 0, 0.5, 1, 2, 3 years of treatment (where SCIT is one of AIT), 15 asthmatic children who did not receive SCIT treatment and 15 healthy children were control groups.
(1) Collecting and pretreating a sample: serum samples from the subjects were collected, centrifuged at 3000rpm for 10 minutes, and the supernatants were collected and stored at-80 ℃ until use.
(2-aminoethyl) trimethyl ammonium chloride hydrochloride (cholamine) is selected as a derivatization reagent to improve the sensitivity and separation efficiency of UHPLC-Q-TOF/MS (ultra high performance liquid chromatography-quadrupole-time of flight/mass spectrometry) for analyzing carboxylic acid;
(2) metabonomic analysis: the serum sample is measured by adopting a multi-platform analysis method, UHPLC-Q-TOF/MS is used for analyzing carboxylic acid, and UHPLC-QQQ-MS is used for quantitatively targeting eicosane compounds;
acquisition and processing of raw LC-MS data using agilent MassHunter qualitative analysis b.06.00 software (agilent technologies, usa). Among them, metabolites with standards were confirmed by comparison with related standards, and other metabolites without standards were confirmed by LC-MS/MS experiments using fragmentation at 30 eV.
(3) Non-targeted metabonomics analysis of potential systemic biomarkers of allergic asthma is carried out by adopting a cholestyramine derived UHPLC-Q-TOF/MS to analyze serum samples of asthmatic patients and healthy people, and adopting SIMCA-P software to carry out multi-factor analysis to determine important differential metabolites between the two groups.
PCA (principal component analysis) results (shown in fig. 2A) confirmed that the healthy group was well separated from the asthmatic group;
in an OPLS-DA (Orthogonal PLS-DA) scoring graph (as shown in fig. 2B), R2Y is 0.893, Q2 is 0.602, and the groups of samples are closely grouped together, indicating that the results of the study in this example are reliable;
in the S-pot plot (as shown in FIG. 2C), a significant increase in 15(S) -HETE in the asthmatic group was determined by comparison of MS and MS/MS results with the standards.
In this example, a difference in the expression level of 125 metabolites, including 15(S) -HETE, was observed and identified from the characteristic MS/MS fragmentation patterns by analyzing the serum non-target metabolomics of asthmatic patients and non-asthmatic controls and comparing the MS data with the data in the lipid map and METLIN database.
Example 2
In this example, the candidate biomarkers were subjected to validation analysis, i.e., the results obtained in example 1 were validated using the t-test, volcano plots, and ROC curves.
(1) Metabolite analysis with significant metabolic differences
FIG. 3A shows the expression variation of different metabolites in asthmatic patients, showing that 42 metabolites are significantly different, showing that asthmatic patients are dysregulated in metabolism, HETEs are up-regulated in asthma
(2) SPSS analysis
The significantly altered metabolites described above were selected for further analysis with SPSS.
According to the analysis results, as shown in FIG. 3B, there are significant content differences among the nine metabolites (AA, 5(S) -HPETE, 12(S) -HPETE, 15(S) -HPETE, 5(S) -HETE, 8(S) -HETE, 11(S) -HETE, 12(S) -HETE, and 15(S) -HETE);
in combination with FIG. 3C, the contents of AA (panel a), 5(S) -HPETE (panel b), 12(S) -HPETE (panel C), 15(S) -HPETE (panel d), 5(S) -HETE (panel e), 8(S) -HETE (panel f), 11(S) -HETE (panel g), 12(S) -HETE (panel h) and 15(S) -HETE (panel i) in healthy humans and asthmatic patients are significantly different; in the figure 3C, the graph a is taken as an example, the left side shows the content of AA in a healthy human body, the right side shows the content of AA in an asthma patient, and the other graphs b-i are consistent with the graph a.
As shown in fig. 3D, the 13 metabolic pathways are shown from top to bottom, in order: (ii) aromatic acid metabolism (arachidonic acid metabolism), fatty acid biosynthesis, beta oxidation of very long chain fatty acids, alpha and linear acid metabolism (alpha-Linolenic acid and Linolenic acid metabolism), mitotic beta-oxidation of short fatty acid metabolism (mitochondrial beta oxidation of short fatty acid metabolism), metabolic synthesis (plasma hormone synthesis), glycerol metabolism (glycerolipid metabolism), mitotic beta-oxidation of medium fatty acid metabolism (mitochondrial beta oxidation of medium fatty acid metabolism), biological acid (bile acid biosynthesis), beta-oxidation of medium fatty acid metabolism (mitochondrial beta oxidation of long fatty acid metabolism), fatty acid biosynthesis (fatty acid metabolism), fatty acid biosynthesis, and fatty acid metabolism (fatty acid metabolism), the nine metabolites are all related to AA metabolism, show potential system target capacity and can distinguish asthma patients from healthy control groups.
Among them, 12(S) -HETE has good AUC values (P <0.05, | FC | >1.2), where FC represents Fold Changes and shows potential systemic target ability, able to distinguish asthmatic patients from healthy controls.
Relevant statistics for the 9 metabolites are shown in table 1:
TABLE 1
As can be seen from the above table, the contents of nine metabolites, namely AA, 5(S) -HPETE, 12(S) -HPETE, 15(S) -HPETE, 5(S) -HETE, 8(S) -HETE, 11(S) -HETE, 12(S) -HETE and 15(S) -HETE, are all obviously up-regulated, and the up-regulation times are 1.29-3.19.
(3) Predicting Variable Importance (VIP score)
In this embodiment, VIP scores are predicted by a PLS-DA (Partial least-squares discriminant analysis) model, and the most important metabolites calculated are shown in fig. 3E.
As can be seen from this example, 15(S) -HETE has a higher AUC of 0.89 and FC of 2.39, FC (asthma/normal), and a higher VIP. Thus, 15(S) -HETE could be a candidate biomarker to monitor the response of SCIT-associated allergic asthma therapy.
Example 3
This example is used for longitudinal studies of SCIT group targeted eicosanoid metabolomics.
SCIT is effective in ameliorating symptoms caused by allergens, and is effective in treating allergic asthma, and the level of immunostimulatory antibody IgE tends to slightly increase in the first year of treatment, but significantly decreases after 1 to 3 years of SCIT. Although several studies suggest IgE and IgG4 as secondary results, there are currently no clearly relevant biomarkers in clinical trials or clinical responses and there are no significant changes in lung function or changes in sige levels in these SCIT patients.
1. In this example, the metabolomics of patients receiving three-year SCIT treatment was analyzed in a targeted manner, and the results are shown in fig. 4A to 4D. The following are found:
12(S) -HPETEs and 12(S) -HETEs (see (I) and (II) in FIG. 4A);
15(S) -HPETEs and 15(S) -HETEs (see (I) and (II) in FIG. 4B);
5(S) -HPETEs and 5(S) -HETEs (see (I) and (II) in FIG. 4C);
the levels of 8(S) -HETES and 11(S) -HETES (see panels (I) and (II) in FIG. 4D) increased dramatically during the first year of treatment and then decreased gradually from 1 to 3 years.
Among these, as shown in figure 5A, 15(S) -HETE levels were significantly lower than baseline levels (0Y, P <0.05) 3 years after treatment. Therefore, SCIT contributes to the treatment of allergic asthma for at least 3 years.
2. In addition, the metabolic pathway of eicosanoids was also analyzed in this example;
eicosanoids are key drivers of inflammatory responses, and LOX and GPx enzymes are involved in allergen immunoregulatory processes and airway epithelial responses.
The results obtained are shown in FIG. 5B, and the Lipoxygenase (LOX) is classified into 5-LOX, 8-LOX, 11-LOX, 12-LOX and 15-LOX according to the specific position of AA oxygenation, and AA is metabolized into 5(S) -HPETEs, 8(S) -HPETEs, 11(S) -HPETEs, 12(S) -HPETEs and 15(S) -HPETEs;
glutathione peroxidase (GPx) is thought to be involved in the synthesis of eicosanoids, metabolizing 5(S) -HPETEs, 12(S) -HPETEs, and 15(S) -HPETEs into 5(S) -, 12(S) -and 15(S) -HETEs by modulating LOX activity.
Since 15(S) -HETE is obtained by metabolizing arachidonic acid through the pathways of 15-LOX and GPx, it is a biomarker involved in allergen-specific immunotherapy of allergic asthma, and due to the change in the expression level, it is presumed that the content of 15-LOX and GPx may also be a biomarker for allergen-specific immunotherapy of allergic asthma.
In summary, in the present invention, the inventors found that 15(S) -HETEs levels were higher in the asthmatic group, and that 15(S) -HETE decreased significantly after receiving allergen-specific immunotherapy; therefore, 15(S) -HETE can be used as a metabolite in serum for monitoring the curative effect of allergen-specific immunotherapy, is also a detection target of allergic asthma, and explains the pathogenesis of allergic asthma according to the expression level of the metabolite.
The applicant declares that the above description is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be understood by those skilled in the art that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are within the scope and disclosure of the present invention.
Claims (10)
- Use of (S) -hydroxyeicosatetraenoic acid as a serological marker in the manufacture of a kit for assessing the effect of an allergen-specific immunotherapy or in the construction of a method for assessing the effect of an allergen-specific immunotherapy.
- 2. The use according to claim 1, wherein the kit for assessing the effect of allergen-specific immunotherapy comprises: a reagent for detecting the content of 15(S) -hydroxyeicosatetraenoic acid.
- 3. The use according to claim 1 or 2, wherein the kit for assessing the effect of an allergen-specific immunotherapy further comprises:and (b) a reagent for detecting the content of any one or at least two serological markers of 5(S) -hydroxyeicosatetraenoic acid, 8(S) -hydroxyeicosatetraenoic acid, 11(S) -hydroxyeicosatetraenoic acid, 12(S) -hydroxyeicosatetraenoic acid, 5(S) -hydroxyeicosatetraenoic acid, 12(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid or arachidonic acid.
- 4. The use according to claim 3, wherein the kit for assessing the effect of allergen-specific immunotherapy comprises:reagents for measuring the content of 15(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid and 12(S) -hydroxyeicosatetraenoic acid.
- 5. The use according to claim 1, wherein the method of assessing the effect of allergen specific immunotherapy comprises:the amount of 15(S) -hydroxyeicosatetraenoic acid in the serum sample is measured and the effect of allergen-specific immunotherapy is evaluated on the basis of the amount.
- 6. The use according to claim 5, wherein the method of assessing the effect of allergen-specific immunotherapy further comprises:detecting the amount of any one or at least two serological markers of 5(S) -hydroxyeicosatetraenoic acid, 8(S) -hydroxyeicosatetraenoic acid, 11(S) -hydroxyeicosatetraenoic acid, 12(S) -hydroxyeicosatetraenoic acid, 5(S) -hydroxyeicosatetraenoic acid, 12(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid or arachidonic acid in a serum sample, and assessing the effect of allergen-specific immunotherapy based on the amount of each said serological marker.
- 7. The use according to claim 5 or 6, wherein in the method of assessing the effect of allergen-specific immunotherapy, the method of detecting the amount of said serological marker comprises: derivatized UHPLC-Q-TOF/MS analysis.
- 8. The use according to claim 7, wherein the method of assessing the effect of allergen-specific immunotherapy comprises pretreating the serum sample by a method comprising:and adding ethyl acetate into the serum sample, wherein the volume ratio of the serum sample to the ethyl acetate is 1 (2-5), centrifuging, collecting the supernatant, and drying under a nitrogen flow.
- 9. The use according to claim 8, wherein the derivatization is carried out by: and mixing the serum sample obtained after the pretreatment, HOBt, HATU and (2-aminoethyl) trimethyl ammonium chloride hydrochloride for reaction.
- Use of a combination of 15(S) -hydroxyeicosatetraenoic acid, 15(S) -hydroxyeicosatetraenoic acid and 12(S) -hydroxyeicosatetraenoic acid as serological markers for the preparation of a kit for evaluating the effect of an allergen-specific immunotherapy or for the construction of a method for evaluating the effect of an allergen-specific immunotherapy.
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| WO2008124187A1 (en) * | 2007-04-10 | 2008-10-16 | University Of Medicine And Dentistry Of Nj | Biochemical markers for disease states and genes for identification of biochemical defects |
| US20130315898A1 (en) * | 2012-05-14 | 2013-11-28 | The Cleveland Clinic Foundation | Biomarkers for asthma |
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