KR102435328B1 - Biomarker composition for diagnosis of asthma containing COPS5 - Google Patents

Abstract

The present invention relates to the use of constitutive photomorphogenesis 9 Signalosome Subunit 5 (COPS5) for diagnosing asthma. The biomarker COPS5 for diagnosing asthma according to the present invention is closely related to lung function, airway hypersensitivity and inflammation. This means that the biomarker COPS5 for diagnosis of asthma of the present invention can predict the diagnosis and pathological state of asthma, and thus can be variously used in the field of diagnosis and treatment of asthma.

Description

Biomarker composition for diagnosis of asthma containing COPS5

The present invention relates to a biomarker COPS5 (Constitutive photomorphogenesis 9 Signalosome Subunit 5) for diagnosing asthma.

Asthma is a chronic inflammatory airway disease characterized by coughing, shortness of breath, and wheezing due to hypersensitivity of the airways to various stimuli. The causes of asthma are known as genetic predisposition, environmental factors such as pollen, house dust mites, animal hair, respiratory viruses, smoking, air pollution, food, and psychological state, environmental change, exercise, and drugs. Asthma has a prevalence of 5-10% in most regions of the world, and in particular, in Korea, the prevalence of asthma continues to increase to 7.6% despite the government's intensive support for research, treatment and management of asthma disease. .

Diagnosis of asthma includes clinical symptoms of reversible airway obstruction; airway hyperresponsiveness, a pathophysiological symptom; and histopathological symptom, airway inflammation. However, it is difficult to perform bronchoscopy in all patients to prove the inflammatory findings of the airways. Therefore, in clinical practice, the diagnosis is confirmed only by proof of reversible airway obstruction and airway hyperresponsiveness, and special tests including various hematological tests are mobilized to indirectly prove the airway inflammation. Accordingly, there is a need to develop test indicators for more accurate asthma diagnosis.

Accordingly, the present inventors completed the present invention by discovering the biomarker COPS5 overexpressed in asthmatic patients as a result of conducting a study on the test index for the diagnosis of asthma.

Accordingly, an object of the present invention is to provide a biomarker composition for diagnosing asthma comprising COPS5.

Another object of the present invention is to provide a composition for diagnosing asthma comprising an agent for measuring the expression of COPS5 or a gene encoding the same.

Another object of the present invention is to provide a diagnostic kit comprising the composition for diagnosing asthma.

Another object of the present invention is to provide a method for providing information on asthma diagnosis and a screening method for a therapeutic agent for asthma.

In order to achieve the above object, the present invention provides a biomarker composition for diagnosing asthma comprising COPS5.

In addition, the present invention is COPS5; Or a gene encoding it; provides a composition for diagnosing asthma comprising an agent for measuring the expression.

The present invention also provides a kit for diagnosing asthma comprising the composition for diagnosing asthma.

The present invention also provides a method for providing information on asthma diagnosis, comprising measuring the expression of COPS5 or a gene encoding the same in a biological sample.

In addition, the present invention comprises the steps of (a) treating a target material to be screened in a biological sample as an experimental group; (b) COPS5 in the experimental group of step (a) and the control group not treated with the target substance; or a gene encoding it; measuring and comparing the expression of the; and (c) COPS5 in the experimental group as compared to the control group as a result of the comparison in step (b); Or a gene encoding it; selecting a target substance that inhibits the expression; provides a screening method for an asthma treatment comprising a.

The biomarker COPS5 for diagnosing asthma according to the present invention is closely related to lung function, airway hypersensitivity and inflammation. This means that the biomarker COPS5 for diagnosis of asthma of the present invention can predict the diagnosis and pathological state of asthma, and thus can be variously used in the field of diagnosis and treatment of asthma.

1 is a diagram showing the results of analyzing the protein expression of the asthma diagnostic biomarker COPS5 discovered through ELISA.
2A is a diagram showing the results of analyzing the correlation between the biomarker COPS5 for diagnosing asthma and the exerted lung capacity according to the present invention.
2B is a diagram showing the results of analyzing the correlation between the biomarker COPS5 for diagnosing asthma according to the present invention and the forced expiratory volume for 1 second.
3A is a diagram schematically illustrating the manufacturing process of an acute asthma mouse model.
3B is a diagram showing the results of evaluating airway hypersensitivity in an acute asthma mouse model.
Figure 3C is a diagram showing the results of evaluating the degree of inflammation in the acute asthma mouse model through the analysis of cells in the bronchoalveolar lavage fluid.
4 is a diagram showing the results of measuring the protein expression level of the asthma diagnostic biomarker COPS5 in a mouse model of acute asthma through western blotting.
5A is a diagram schematically illustrating the manufacturing process of a chronic asthma mouse model.
5B is a diagram showing the results of evaluating airway hypersensitivity in a mouse model of chronic asthma.
5C is a diagram showing the results of evaluating the degree of inflammation in a mouse model of chronic asthma through analysis of cells in bronchoalveolar lavage fluid.
6 is a diagram showing the results of measuring the protein expression level of the asthma diagnostic biomarker COPS5 in a mouse model of chronic asthma through western blotting.

Hereinafter, the present invention will be described in detail.

According to an aspect of the present invention, the present invention provides a biomarker composition for diagnosing asthma comprising COPS5.

In the present invention, COPS5 (Constitutive photomorphogenesis 9 Signalosome Subunit 5) is one of eight subunits of the COP9 signalosome, and plays an important regulator role in multiple signal transduction pathways. The COPS5 is involved in the degradation of the cyclin-dependent kinase inhibitor CDKN1B/p27Kip1 and is known as a coactivator that increases the specificity of the JUN/AP1 transcription factor.

In the present invention, asthma is a disease in which cough, wheezing, shortness of breath, and chest tightness repeatedly occur due to severe narrowing of the bronchi due to inflammation of the bronchi when exposed to a specific triggering substance. Asthma can be divided into allergic asthma or non-allergic asthma according to the manifestation of allergic characteristics.

In an embodiment of the present invention, the asthma may be allergic asthma or non-allergic asthma, but is not limited thereto.

In a preferred embodiment of the present invention, the allergic asthma or non-allergic asthma is preferably a reduced forced vital capacity (FVC) or forced expiratory volume in one second (FEV1). , but not limited thereto.

In the present invention, diagnosis means confirming the presence or characteristics of a pathological condition. The diagnosis can provide objective basic information necessary for monitoring not only the onset of the disease, but also the prognosis, the progress of asthma, the stage, and the like, and the clinical judgment or opinion of the doctor is excluded. For the purposes of the present invention, diagnosis means ascertaining the onset, prognosis, course, staging or characteristics of asthma.

In the present invention, the biomarker can also be used as a diagnostic marker, is a substance that can be diagnosed by distinguishing whether or not asthma occurs in a biological sample, and shows an increase or decrease in expression in a sample collected from an asthmatic patient compared to a normal sample. organic biomolecules such as polypeptides or nucleic acids (eg, mRNA, etc.), lipids, glycolipids, glycoproteins or sugars (monosaccharides, disaccharides, oligosaccharides, etc.), and the like.

In an embodiment of the present invention, it is preferred that the COPS5 is overexpressed in blood.

In an embodiment of the present invention, it was confirmed that asthma patients overexpressing COPS5 in a blood sample have high airway hypersensitivity and an increased degree of inflammation, which can be usefully used as a biomarker for diagnosing asthma.

According to another aspect of the present invention, the present invention is COPS5; Or a gene encoding it; provides a composition for diagnosing asthma comprising an agent for measuring the expression.

In the present invention, the COPS5; or a gene encoding it; the agent for measuring the expression of a marker by specifically binding to a protein of COPS5 or mRNA encoding the same, which is a marker whose expression is increased in a biological sample of an asthma patient, as described above, and checking the expression level thereof. molecules that can be used for the detection of

In an embodiment of the present invention, the agent for measuring the expression is an oligopeptide, monoclonal antibody, polyclonal antibody, chimeric antibody, ligand, PNA (Peptide nucleic acid) that specifically binds to the COPS5. Or it may be an aptamer.

In the present invention, an antibody refers to a specific protein molecule directed to an antigenic site as a term known in the art. For the purpose of the present invention, an antibody refers to an antibody that specifically binds to COPS5, a marker of the present invention, and the antibody is a protein encoded by the marker gene by cloning each gene into an expression vector according to a conventional method. can be obtained and prepared by a conventional method from the obtained protein. This also includes partial peptides that can be made from the protein. The form of the antibody of the present invention is not particularly limited, and a part thereof is also included in the antibody of the present invention as long as it has polyclonal antibody, monoclonal antibody, or antigen-binding property, and all immunoglobulin antibodies are included. Furthermore, the antibody of the present invention includes a special antibody such as a humanized antibody.

The antibody used for the detection of the biomarker for diagnosis of asthma of the present invention includes a functional fragment of an antibody molecule as well as a complete form having two full-length light chains and two full-length heavy chains. A functional fragment of an antibody molecule refers to a fragment having at least an antigen-binding function, and includes Fab, F(ab'), F(ab') 2 and Fv.

In an embodiment of the present invention, the agent for measuring the expression may be an antisense oligonucleotide, a primer pair or a probe that specifically binds to the gene encoding the COPS5.

In the present invention, the primer is a nucleic acid sequence having a short free 3' hydroxyl group and can form a complementary template and base pair, and serves as a starting point for template strand copying. It means a short nucleic acid sequence that Primers are capable of initiating DNA synthesis in the presence of reagents for polymerization (ie, DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates in appropriate buffers and temperatures. Specifically, by performing PCR amplification using sense and antisense primers of the polynucleotide of COPS5, asthma can be diagnosed based on whether a desired product is produced. PCR conditions, the length of the sense and antisense primers can be modified based on what is known in the art.

In the present invention, the probe refers to a nucleic acid fragment such as RNA or DNA corresponding to several bases to several hundred bases as long as possible to achieve specific binding to mRNA, and is labeled to confirm the presence or absence of a specific mRNA. . The probe may be manufactured in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, an RNA probe, or the like. Selection of appropriate probes and hybridization conditions can be modified based on those known in the art.

The primers or probes of the present invention can be chemically synthesized using the phosphoramidite solid support method, or other well-known methods. Such nucleic acid sequences may also be modified using a number of means known in the art. Non-limiting examples of such modifications include methylation, encapsulation, substitution with one or more homologues of natural nucleotides, and modifications between nucleotides, such as uncharged linkages such as methyl phosphonates, phosphotriesters, phosphoro amidates, carbamates, etc.) or charged linkages (eg phosphorothioates, phosphorodithioates, etc.).

According to another aspect of the present invention, there is provided a kit for diagnosing asthma comprising the composition for diagnosing asthma.

In an embodiment of the present invention, the kit may be an RT-PCR kit, a DNA chip kit, or a protein chip kit, but is not limited thereto.

The kit includes COPS5; Or a gene encoding it; as well as an agent for measuring the expression, tools, reagents, etc. commonly used in the art used for immunological analysis may be included.

Examples of the tool or reagent include, but are not limited to, a suitable carrier, a labeling material capable of generating a detectable signal, chromophores, solubilizers, detergents, buffers, stabilizers, and the like. When the labeling material is an enzyme, it may include a substrate capable of measuring enzyme activity and a reaction terminator. The carrier includes a soluble carrier and an insoluble carrier, and an example of the soluble carrier is a physiologically acceptable buffer known in the art, for example, PBS, and an example of the insoluble carrier is polystyrene, polyethylene, polypropylene, polyester, poly It may be acrylonitrile, fluororesin, crosslinked dextran, polysaccharide, polymer such as magnetic fine particles plated with metal on latex, other paper, glass, metal, agarose, and combinations thereof.

In an embodiment of the present invention, the kit may further include the above-described biomarker composition for diagnosing asthma, and redundant descriptions thereof are omitted to avoid excessive complexity of the present specification.

According to another aspect of the present invention, the present invention provides a method for providing information on the diagnosis of asthma, comprising measuring the expression of COPS5 or a gene encoding the same in a biological sample.

The diagnosis information is measurement information on the expression of COPS5 in asthmatic patients, and for the purposes of the present invention, when the expression of COPS5 is measured to be increased, symptoms of asthma (ie, decreased lung function, increased airway hypersensitivity, increased inflammation) ), and based on this, the present invention provides information on whether an individual has asthma.

In the present invention, measuring the expression of COPS5 is a process of confirming the presence and expression level of a protein expressed in a biological sample for the diagnosis of asthma. to check the quantity. Analysis methods for this include western blotting, ELISA (enzyme linked immunosorbent assay), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, and rocket immunoelectrolysis. Electrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, FACS and protein chip, but are not limited thereto.

In the present invention, measuring the expression of the gene encoding COPS5 is a process of confirming the presence and level of mRNA of a biomarker gene for diagnosing asthma in a biological sample for diagnosing asthma, and can be determined by measuring the amount of mRNA. have. For this, analysis methods include RT-PCR, competitive RT-PCR (RT-PCR), real-time RT-PCR (RT-PCR), RNase protection assay (RPA; RNase protection assay), Northern blotting (Northern blotting). blotting) or a DNA chip, but is not limited thereto.

The biological sample may be blood, plasma, serum, urine, saliva or tissue, but is not limited thereto.

According to another aspect of the present invention, there is provided a screening method for a therapeutic agent for asthma. The method comprises the steps of (a) treating a target material to be screened in a biological sample as an experimental group; (b) COPS5 in the experimental group of step (a) and the control group not treated with the target substance; or a gene encoding it; measuring and comparing the expression of the; and (c) COPS5 in the experimental group as compared to the control group as a result of the comparison in step (b); or a gene encoding it; selecting a target substance that inhibits the expression.

In step (c), the target substance is COPS5 of the experimental group; Or, when the expression of a gene encoding it is suppressed, it may be selected as a therapeutic agent for asthma.

Duplicate content is omitted in consideration of the complexity of the present specification, and terms not defined otherwise in the present specification have the meanings commonly used in the technical field to which the present invention pertains.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not to be construed as being limited by these examples.

Experimental Example 1. Preparation of acute asthma mouse model

The process of constructing an acute asthma mouse model is briefly shown in FIG. 3A . Specifically, BALB/c mice (female, 6 weeks old) (Orient Bio, Seongnam, Korea) were grade V chicken egg OVA (Sigma-Aldrich, St Louis, MO) 50 μg was sensitized by intraperitoneal injection (IP) on days 0 and 14. On days 21-23, all mice were administered intranasal (IN) 150 μg of grade III OVA (Sigma-Aldrich) (in D-PBS). Control mice were administered saline instead of OVA. On day 24, airway hyperresponsiveness (AHR) was measured, and bronchoalveolar lavage fluid (BALF) was obtained. Proteins were also obtained from mouse lung tissue.

Experimental Example 2. Chronic asthma mouse model production

The chronic asthma mouse model production process is briefly shown in FIG. 5A, and the chronic asthma mouse model was divided into three groups according to the day of sacrifice (33, 44, and 80 days).

First, BALB/c mice (female, 6 weeks old) (Orient Bio, Seongnam, Korea) were treated with grade V chicken egg OVA (Sigma-Aldrich, St) emulsified in 10 mg of hydroxyl aluminum and D-PBS (Dulbecco's phosphate buffered saline). Louis, MO) was sensitized by intraperitoneal injection (IP) of 50 μg on days 0 and 14. All mice were intranasally administered with 150 μg of grade III OVA (Sigma-Aldrich) (in 50 μl D-PBS) on days 0, 14, 28, 29, 29, 30, and 32. On day 33, airway hyperresponsiveness (AHR) was measured, and bronchoalveolar lavage fluid (BALF) was obtained. Proteins were also obtained from mouse lung tissue.

The remaining mice with established AHR were intranasally administered 150 μg of grade III OVA (Sigma-Aldrich) on day 44. AHR was measured on day 45 and BALF was obtained. Proteins were also obtained from mouse lung tissue.

The remaining mice were intranasally administered with 150 μg of grade III OVA (Sigma-Aldrich) once a week for a period of 52 to 77 days, and additionally administered on day 79. AHR was measured at day 80 and BALF was obtained. Proteins were also obtained from mouse lung tissue.

Experimental Example 3. Airway hypersensitivity evaluation

For airway hypersensitivity analysis, asthma mouse models were anesthetized by administering tiletamine and xylazine (Zoletil and lumpum; Bayer Korea Co., Seoul, Korea) (2 mg/kg). Concentrations (0, 5, 20 or 100 mg/ml) were administered and then evaluated.

Experimental Example 4. Inflammation evaluation through bronchoalveolar lavage analysis

After centrifugation of the bronchoalveolar lavage, the supernatant was collected and stored at -20°C. In addition, the cell pellet was resuspended for cell counting, and a cytospin slide was prepared for cell differentiation (500 cells/mouse, Diff-Quick-staining). Total cells included, macrophages, eosinophils, neutrophils and lymphocytes were counted.

Experimental Example 5. Western Blotting

Lung tissue was homogenized in protein lysis buffer (50 mM Tris-HCL (pH 7.4), 50 mM NaCl, 0.1% SDS, 1% Triton X-100, 0.5 mM EDTA and 100 mM PMSF in distilled water), and centrifuged at 4°C. (14000 rpm, 30 min) to obtain a protein. Mouse lung proteins were separated by SDS-PAGE and transferred to PVDF membrane. The membrane to which the mouse lung protein was transferred was blocked with 5% BSA (in 0.1% Tween 20 in TBS) at room temperature for 2 hours and then washed. Rabbit anti-COPS5 (1:1000, ABclonal, Massachusetts, USA), a primary antibody, was incubated overnight at 4°C and washed with the washed membrane. The washed membrane was treated with HRP-conjugated secondary antibody and incubated. After completion of the culture, the protein was detected using WEST-ZOL plus Western Blot Detection System (iNtRon, SungNam, Korea). The relative amount of protein was determined by quantitative densitometry and normalized to beta-actin (Sigma-Aldrich).

Experimental Example 6. ELISA (Enzyme linked immunosorbent assay)

COPS5 in plasma was characterized by ELISA (Mybio, Minneapolis, Minn.). For comparison of results with other plates, the optical density (OD) of the test sample was adjusted with the positive and negative control samples provided in each kit. In addition, the average OD of duplicate wells was calculated, and the index value of each plasma was calculated by the following equation.

index value = (OD of plasma tested - OD of negative control) / (OD of positive control - OD of negative control) × 100

Example 1. Discovering biomarkers for diagnosing asthma

In order to discover biomarkers for the diagnosis of asthma, protein levels in plasma of asthmatic patients and normal persons were analyzed by ELISA. Specifically, this experiment was divided into a normal group (control subject), stable asthma group, and exacerbated asthma group, and the specific details of the experimental group are as follows.

- Normal group: group without confirmed asthma or lung disease

- Controlled asthma group: A group of asthma patients who were diagnosed with asthma and had reduced lung function but whose symptoms were controlled with medications.

- Exacerbated asthma group: Asthma patient group with confirmed asthma, decreased lung function and increased number of inflammatory cells

Plasma of the experimental group was collected, and protein levels were analyzed by ELISA.

As a result, COPS5 with significantly increased protein levels was discovered in the exacerbated asthmatic group.

The results of confirming the expression of COPS5 in the normal control group, the controlled asthma group and the exacerbated asthma group through ELISA are shown in FIG. 1 .

As shown in FIG. 1 , it was confirmed that the expression of COPS5 was significantly increased in the exacerbated asthma group compared to the normal control group and the controlled asthma group.

Based on the ELISA results, the expression level of COPS5 in the controlled asthma group and the exacerbated asthma group; and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1);

As shown in FIG. 2A , it was confirmed that the expression level of COPS5 and the exerted lung capacity were correlated. More specifically, the association was inversely correlated, and the association was stronger in the exacerbated asthma group.

As shown in FIG. 2B , it was confirmed that the expression level of COPS5 and the forced expiratory volume in 1 second were correlated. More specifically, the association was inversely correlated, and the association was stronger in the exacerbated asthma group.

Example 2. Expression of biomarker COPS5 for diagnosing asthma in mouse model of acute asthma

2-1. Airway hypersensitivity assessment

Airway hypersensitivity according to the concentration of methacholine was evaluated in a mouse model of acute asthma. A control group (shame) in this experiment is a mouse administered with saline during model production. The results of airway hypersensitivity evaluation are shown in FIG. 3B .

As shown in FIG. 3B , the acute asthma mouse model had higher airway hypersensitivity than the control group, which was confirmed to be dependent on the concentration of methacholine.

2-2. Inflammation Assessment

The degree of inflammation in the acute asthma mouse model was evaluated through cell analysis in bronchoalveolar lavage fluid. A control group (shame) in this experiment is a mouse administered with saline during model production. The inflammation evaluation results are shown in FIG. 3C .

As shown in FIG. 3C , it was confirmed that the acute asthma mouse model had more cells in the bronchoalveolar lavage fluid than the control group. In particular, it was confirmed that the number of macrophages and neutrophils was large. This means that the level of inflammation in the acute asthma mouse model was significantly increased compared to the control group.

2-3. Measurement of the expression level of COPS5

The protein expression level of the biomarker COPS5 for diagnosing asthma was measured in the acute asthma mouse model. The protein expression level was measured by Western blotting. The measurement result of COPS5 expression level is shown in FIG. 4 .

As shown in FIG. 4 , it was confirmed that the acute asthma mouse model expressed high COPS5 compared to the control group.

Example 3. Expression of the biomarker COPS5 for diagnosing asthma in a mouse model of chronic asthma

3-1. Airway hypersensitivity assessment

Airway hypersensitivity according to the concentration of methacholine was evaluated in a mouse model of chronic asthma. A control group (shame) in this experiment is a mouse administered with saline during model production. The results of airway hypersensitivity evaluation are shown in FIG. 5B .

As shown in FIG. 5B , the chronic asthma mouse model had higher airway hypersensitivity than the control group, which was confirmed to be dependent on the concentration of methacholine. In addition, the chronic asthma mouse model confirmed that the earlier the sacrifice date, the higher the airway hypersensitivity.

In addition, it can be seen that the asthma mouse model sacrificed on the 80th day had lower airway hypersensitivity compared to that sacrificed on the 33rd day. It seems that airway hypersensitivity is relatively low due to low sensitivity due to airway remodeling when exposed to allergens for a long time.

3-2. Inflammation Assessment

The degree of inflammation in a mouse model of chronic asthma was evaluated through analysis of cells in bronchoalveolar lavage fluid. A control group (shame) in this experiment is a mouse administered with saline during model production. The inflammation evaluation result is shown in FIG. 5C.

As shown in FIG. 5C , it was confirmed that the chronic asthma mouse model had more cells in the bronchoalveolar lavage fluid than the control group. In particular, it was confirmed that the number of macrophages and neutrophils was large. This means that the level of inflammation in the chronic asthma mouse model was significantly increased compared to the control group. In addition, the chronic asthma mouse model confirmed that the earlier the sacrifice day, the greater the number of total cells, macrophages and eosinophils (that is, the higher the degree of inflammation).

In addition, it can be seen that the chronic asthma mouse model sacrificed on day 80 had a lower level of inflammation compared to that sacrificed on day 33. It seems that the degree of inflammation is relatively low due to decreased sensitivity due to airway remodeling when exposed to allergens for a long period of time.

3-3. Measurement of expression level of COPS5

In the chronic asthma mouse model (33 days and 80 days), the protein expression level of the biomarker COPS5 for diagnosing asthma was measured. The protein expression level was measured by Western blotting. The measurement result of COPS5 expression level is shown in FIG. 6 .

As shown in FIG. 6 , it was confirmed that the chronic asthma mouse model exhibited high COPS5 expression compared to the control group. It was confirmed that the chronic asthma mouse model sacrificed on day 80 had a higher expression of COPS5 compared to the model sacrificed on day 33.

As previously confirmed, the chronic asthma mouse model confirmed that the expression of COPS5 was increased even though airway hypersensitivity and inflammation were low, and thus can be utilized as a biomarker for asthma diagnosis.

Overall, the present inventors discovered COPS5 as a biomarker for diagnosing asthma, and confirmed that the biomarker is closely related to lung function, airway hypersensitivity and inflammation. This means that the biomarker COPS5 for diagnosis of asthma of the present invention can predict the diagnosis and pathological state of asthma, and thus can be used in various fields in the diagnosis and treatment of asthma.

Above, a specific part of the present invention has been described in detail, for those of ordinary skill in the art, it is clear that this specific description is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, it is intended that the substantial scope of the present invention be defined by the appended claims and their equivalents.

Claims (11)

A composition for diagnosing asthma, comprising an agent for measuring the expression of COPS5 (Constitutive photomorphogenesis 9 Signalosome Subunit 5) in blood. The method of claim 1,
The asthma is allergic asthma or non-allergic asthma, asthma diagnosis composition. The method of claim 1,
The asthma is a forced vital capacity (forced vital capacity, FVC) or forced expiratory volume in one second (forced expiratory volume in one second, FEV1) is reduced, the composition for diagnosing asthma. The method of claim 1,
The COPS5 is overexpressed in blood, asthma diagnostic composition. delete The method of claim 1,
The agent for measuring the expression is an oligopeptide, monoclonal antibody, polyclonal antibody, chimeric antibody, ligand, PNA (Peptide nucleic acid) or aptamer that specifically binds to the COPS5. , A composition for diagnosing asthma. delete A kit for diagnosing asthma comprising the composition of any one of claims 1 to 4 and 6. 9. The method of claim 8,
The asthma diagnosis kit is an RT-PCR kit, a DNA chip kit or a protein chip kit. A method for providing information on the diagnosis of asthma, comprising the step of measuring the expression of COPS5 in blood. delete

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