WO2018030452A1 - Diagnostic marker for schizophrenia and related disorders, and application for diagnostic marker for schizophrenia and related disorders - Google Patents

Abstract

A diagnostic marker for schizophrenia-related disorders that comprises an anti-syncytin-1 antibody.

Description

Diagnostic markers for schizophrenia and related diseases and uses thereof

The present invention relates to a diagnostic marker for schizophrenia and related diseases and use thereof. More specifically, a diagnostic marker for schizophrenia-related disease, a diagnostic kit for schizophrenia-related disease, a method of collecting data for identifying whether a subject has schizophrenia-related disease, And a method for testing whether a subject suffers from schizophrenia-related disease. This application claims priority based on Japanese Patent Application No. 2016-158681 filed in Japan on August 12, 2016, the contents of which are incorporated herein by reference.

Schizophrenia is a type of mental illness characterized by symptoms such as hallucinations and delusions. As a result, the functions of living in the family and society are impaired while interacting with people (disability of life). It also has the feature that it is difficult to think back by thinking that "senses, thoughts, and actions are distorted due to illness" (disorder of disease). Schizophrenia is likely to follow a chronic course, and it is believed that the disease progresses several years after the onset of the disease, causing irreversible disability and permanent impairment of social functions.

The incidence of schizophrenia reaches 0.5 to 1.0% of the population, so the number of patients is very large. However, since the diagnosis is highly dependent on the specific diagnostic criteria of the psychiatrist, the current situation is to rely on the skills of experienced doctors. For this reason, there are many cases in which therapeutic intervention is delayed, resulting in intractable cases.

On the other hand, in the human genome, there are DNA sequences that are considered to be derived from a retrovirus called human endogenous retrovirus (HERV). Most of the sequences are inactivated as a result of years of mutation and fragmentation. However, HERV-W, one of about 30 types of HERV, encodes a viral envelope protein (ENV) in a translatable state, and its translation product, syncytin-1, is present during placenta formation. It is known to play an important role in the cell fusion process.

For example, Non-Patent Document 1 reports that syncytin-1 is ectopicly expressed outside the placenta in diseases such as multiple sclerosis and schizophrenia.

Perron H., et al., Endogenous retrovirus type W GAG and envelope protein antigenemia in serum of schizophrenic patients., Biol. Psychiatry, 64 (12), 1019-1023, 2008.

Under such circumstances, there is a demand for a diagnostic method based on an objective standard that allows a non-specialist doctor to correctly suspect the onset of schizophrenia. Then, an object of this invention is to provide the technique which can diagnose the schizophrenia related disease objectively.

The present invention includes the following aspects.
[1] A marker for diagnosing schizophrenia-related disease, comprising an anti-syncytin-1 antibody.
[2] A kit for diagnosing schizophrenia-related disease, comprising syncytin-1 protein or a fragment thereof.
[3] The kit for diagnosis of schizophrenia-related disease according to claim 2, further comprising a specific binding substance for a human antibody.
[4] A fragment of syncytin-1 protein, wherein the fragment is a peptide consisting of the amino acid sequence set forth in SEQ ID NO: 9, or one or several amino acids are missing from the amino acid sequence set forth in SEQ ID NO: 9. The diagnostic kit for a schizophrenia-related disease according to [2] or [3], which is a peptide consisting of a deleted, substituted or added amino acid sequence and recognized by an anti-syncytin-1 antibody.
[5] A method for collecting data for serologically identifying the possibility that a subject is suffering from schizophrenia-related disease, wherein anti-syncytin-1 antibody is present in blood from the subject The presence or absence of the antibody is data for serologically identifying the possibility that the subject is suffering from schizophrenia-related disease.
[6] The method according to [5], wherein the step of detecting whether or not an anti-cincytin-1 antibody is present is performed by an ELISA method.
[7] A step of detecting whether or not the anti-scincytin-1 antibody is present in the blood derived from the subject, and if the antibody is present, the subject may suffer from schizophrenia-related disease Test whether the subject is afflicted with schizophrenia-related disease by comparing to the criteria that the subject is not afflicted with schizophrenia-related disease in the absence of the antibody how to.
[8] The method according to [7], wherein the step of detecting whether or not an anti-cincytin-1 antibody is present is performed by an ELISA method.

According to the present invention, a technique capable of objectively diagnosing schizophrenia-related diseases can be provided.

10 is a graph showing the results of epitope mapping in Experimental Example 3. 6 is a graph showing the detection results of anti-scincytin-1 antibody in Experimental Example 5. (A) to (e) are graphs showing the detection results of anti-syncytin-1 antibody in Experimental Example 6.

[Diagnosis marker for schizophrenia-related diseases]
In one embodiment, the present invention provides a diagnostic marker for schizophrenia-related diseases, comprising an anti-scincytin-1 antibody. Here, the anti-syncytin-1 antibody is an antibody specific for the syncytin-1 protein. Syncytin-1 protein is also called ERVW-1. The amino acid sequence of the syncytin-1 protein is shown in SEQ ID NO: 1.

As used herein, schizophrenia-related disease means a mental disorder that requires therapeutic intervention, and more specifically, schizophrenia, an intermediate form of schizophrenia and manic depression, manic depression, And personality disorder.

As will be described later in Examples, the inventors have found that anti-scincytin-1 antibody is present in the blood of patients with some schizophrenia-related diseases. In addition, the present inventors have found that anti-syncytin-1 antibody is not substantially present in the blood of healthy people.

Some patients with schizophrenia-related diseases do not have anti-syncytin-1 antibody, and it is impossible to determine whether such patients are schizophrenia-related diseases. However, if anti-scincytin-1 antibody is detected in the blood of a patient suspected of suffering from schizophrenia-related disease, the patient can be objectively determined to be schizophrenia-related disease. .

The marker according to the present embodiment enables an objective diagnosis of schizophrenia-related disease, which is extremely difficult because there is no currently useful diagnostic method, for some patients. For this reason, the marker of this embodiment is useful.

The anti-syncytin-1 antibody can be obtained by, for example, contacting a syncytin-1 protein immobilized on a solid phase with serum or plasma derived from a subject, and subsequently detecting the antibody derived from the subject bound to the above-mentioned syncytin-1 protein. Or the like. Examples of the subject-derived antibody include IgG antibody, IgM antibody, IgA antibody, and the like.

This embodiment can also be said to provide the use of an anti-scincytin-1 antibody as a diagnostic marker for schizophrenia-related diseases.

[Diagnostic kit for schizophrenia-related diseases]
In one embodiment, the present invention provides a kit for diagnosing schizophrenia-related disease comprising syncytin-1 protein or a fragment thereof. With the kit of the present embodiment, it can be objectively determined whether or not the subject suffers from schizophrenia-related disease.

As the syncytin-1 protein, the full-length protein consisting of the amino acid sequence shown in SEQ ID NO: 1 may be used, or a fragment of the syncytin-1 protein may be used. In addition, the syncytin-1 protein may have a tag such as a histidine tag or a GST (glutathione-S-transferase) tag at the N-terminus or C-terminus. By having a tag, for example, a syncytin-1 protein can be easily prepared.

The fragment of the syncytin-1 protein may be, for example, a peptide consisting of the 30th to 58th amino acid sequence of the amino acid sequence described in SEQ ID NO: 1, or the 193th to 221th amino acid sequence of SEQ ID NO: 1. It may be a peptide consisting of the amino acid sequence of position No. 1, or a peptide consisting of the amino acid sequence of positions 493 to 521 (SEQ ID NO: 9) of the amino acid sequence shown in SEQ ID NO: 1. Moreover, the partial peptide of these peptides may be sufficient.

The fragment of the syncytin-1 protein is the amino acid sequence described above, that is, the amino acid sequence of the 30th to 58th, the 193th to 221nd, and the 493th to 521st (SEQ ID NO: 9) amino acid sequences shown in SEQ ID NO: 1. It may be a peptide consisting of an amino acid sequence in which one or several amino acids are deleted, substituted or added, and recognized by an anti-scincytin-1 antibody.

Here, for example, the number may be 2 to 10, 2 to 8, 2 to 6, or 2 to 4. Also good. This is because an epitope usually consists of 6 to 8 amino acid residues. In addition, it can be said that the anti-scincytin-1 antibody is recognized as being recognized by the anti-scincytin-1 antibody.

The fragment of the syncytin-1 protein is a peptide having an amino acid sequence containing the 30th to 58th, the 193th to 221nd, or the 493th to 521st (SEQ ID NO: 9) of the amino acid sequence shown in SEQ ID NO: 1. May be.

As will be described later in the Examples, the inventors have revealed that the anti-syncytin-1 antibody present in the blood of patients with schizophrenia-related diseases has the above-mentioned partial peptide of the syncytin-1 protein as an epitope. I made it. Therefore, anti-syncytin-1 antibody can be detected using the above peptide as an antigen. Peptides are easy to handle because they can be chemically synthesized.

For example, by immobilizing syncytin-1 protein or a fragment thereof on a solid phase, contacting serum or plasma derived from a subject, and detecting the binding between the syncytin-1 protein or fragment thereof and an anti-syncytin-1 antibody The presence of anti-scincytin-1 antibody can be detected.

The binding between the syncytin-1 protein or a fragment thereof and the anti-scincytin-1 antibody is, for example, a surface plasmon resonance immunoassay using Biacore (trade name, GE Healthcare Japan) or the like, AFFINIXQ (trade name, Initium). It is possible to detect by a quartz vibrator type immunosensor system using an enzyme, etc., an enzyme linked immunosorbent assay (ELISA) method, a Western blotting method or the like.

The diagnostic kit for schizophrenia-related disease of this embodiment may further include a specific binding substance for human antibodies. Thereby, it becomes a more suitable structure in order to implement ELISA method, a Western blotting method, etc. For example, the syncytin-1 protein on the solid phase is immobilized by immobilizing the syncytin-1 protein or a fragment thereof on the solid phase, contacting serum or plasma derived from a subject, and then reacting with a specific binding substance for a human antibody. Alternatively, anti-syncytin-1 antibody bound to the fragment can be detected. The ELISA method and Western blotting method are already widely used as clinical test methods in many antibody measurements.

Here, examples of the human antibody include an IgG antibody and an IgM antibody. Specific binding substances include antibodies, antibody fragments, aptamers and the like. Examples of antibody fragments include Fv, Fab, scFv and the like. The above antibody may be a monoclonal antibody or a polyclonal antibody. A commercially available antibody may also be used.

[Data collection method]
In one embodiment, the present invention relates to a method for collecting data for serologically identifying the likelihood that a subject has a schizophrenia-related disease, wherein the anti-syncytin is collected in blood from the subject. −1 detecting whether or not the antibody is present, the presence or absence of the antibody is data for serologically identifying the possibility that the subject has a schizophrenia-related disease. Provide a way. The method of this embodiment does not include the step of determining whether or not the subject suffers from schizophrenia-related disease.

In the method of the present embodiment, as the syncytin-1 protein or a fragment thereof, the same as described above can be used.

The above-mentioned step of detecting whether or not an antibody specific for syncytin-1 protein or a fragment thereof is present in blood derived from a subject brings the serum or plasma from the subject into contact with the syncytin-1 protein or a fragment thereof And a step of detecting a subject-derived antibody bound to the syncytin-1 protein or a fragment thereof.

In the method of the present embodiment, the above-described step of detecting whether or not anti-syncytin-1 antibody is present may be performed by an ELISA method. As will be described later in the Examples, the inventors have clarified that the ELISA method can detect an anti-cincytin-1 antibody with higher sensitivity than the Western blotting method. However, when considering the specificity, it is recommended to use the Western blotting method together with the ELISA method.

The serum or plasma derived from the subject is preferably diluted 1/100 to 1/10000 in order to prevent non-specific reaction. The dilution ratio of serum or plasma derived from a subject may be, for example, 1/100 to 1/5000, for example, 1/100 to 1/1000, for example, 1/100 to 1/500. Also good.

If the anti-syncytin-1 antibody is present in the blood derived from the subject, it can be determined that the subject is suffering from schizophrenia-related disease.

[Method for testing whether a subject has schizophrenia-related disease]
In one embodiment, the present invention comprises a step of detecting whether or not an anti-scincytin-1 antibody is present in blood derived from a subject, and in the presence of the antibody, the subject is a schizophrenia-related disease. The subject is suffering from schizophrenia-related disease by comparing to the criteria that the subject is not suffering from schizophrenia-related disease in the absence of the antibody. Provide a method to test whether or not. The method of this embodiment may further include a step of clinically confirming whether or not the subject is suffering from schizophrenia-related disease.

In the method of the present embodiment, as the syncytin-1 protein or a fragment thereof, the same as described above can be used.

The above-mentioned step of detecting whether or not an antibody specific for syncytin-1 protein or a fragment thereof is present in blood derived from a subject brings the serum or plasma from the subject into contact with the syncytin-1 protein or a fragment thereof And a step of detecting a subject-derived antibody bound to the syncytin-1 protein or a fragment thereof. Serum or plasma derived from the subject can be used at the same dilution rate as described above.

In the method of the present embodiment, the above-described step of detecting whether or not anti-syncytin-1 antibody is present may be performed by an ELISA method. As will be described later in the Examples, the inventors have clarified that the ELISA method can detect an anti-cincytin-1 antibody with higher sensitivity than the Western blotting method. However, although the ELISA method has high sensitivity, the specificity may be slightly reduced. For this reason, it is preferable to use together the ELISA method and the Western blotting method. Usually, it is preferable to first perform serum screening by ELISA and confirm a positive sample by Western blotting.

[Other Embodiments]
In one embodiment, the present invention comprises a step of contacting a serum or plasma derived from a subject with a syncytin-1 protein or a fragment thereof, and a step of detecting an antibody derived from the subject bound to the syncytin-1 protein or a fragment thereof. Providing a method for diagnosing schizophrenia-related disease, comprising: determining that the subject is suffering from schizophrenia-related disease when the antibody is detected.

In the diagnostic method of the present embodiment, the same as described above can be used as the syncytin-1 protein or a fragment thereof. Also, serum or plasma derived from a subject can be used at the same dilution rate as described above.

In the diagnostic method of the present embodiment, the above-described step of detecting anti-syncytin-1 antibody may be performed by ELISA. As will be described later in the Examples, the inventors have clarified that the ELISA method can detect an anti-cincytin-1 antibody with higher sensitivity than the Western blotting method. However, as described above, the ELISA method has high sensitivity, but the specificity may be slightly reduced. For this reason, it is preferable to use together the ELISA method and the Western blotting method. Also in the diagnostic method of this embodiment, it is preferable to first perform serum screening by ELISA and confirm a positive sample by Western blotting.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

[Experimental Example 1]
(Preparation of syncytin-1 protein using E. coli)
A syncytin-1 expression plasmid optimized for the codon of E. coli was chemically synthesized and inserted into pET (Novagen), which is a protein expression vector for E. coli, to prepare a syncytin-1 expression plasmid. This was introduced into BL21-CodonPlus (DE3) -RIPL competent cell (Agilent Technologies) and cultured in the presence of 1 mM IPTG (Isopropyl β-D-1-thiogalactopyroside) for 4 hours at 20 ° C. Induced. Since the expressed syncytin-1 protein had a histidine tag at the N-terminus, it was partially purified using a HisTrap FF column (GE Healthcare Japan) and then subjected to electrophoresis using a 10% acrylamide gel. The band was cut out and purified to obtain syncytin-1 protein.

[Experiment 2]
(Detection of anti-syncytin-1 antibody in serum)
Anti-syncytin-1 antibody was detected in the serum by Western blotting. Specifically, the purified syncytin-1 protein was first separated by 10% SDS-polyacrylamide gel electrophoresis (PAGE), and then transferred to a polyvinylidene fluoride (PVDF) membrane by a conventional method. Subsequently, serum derived from the subject was diluted to 1/300 and reacted with the PVDF membrane. Subsequently, the PVDF membrane was reacted with a horseradish peroxidase (HRP) -labeled anti-human IgG antibody, and further an HRP substrate was reacted to detect an anti-cincytin-1 antibody.

The subjects included patients diagnosed with schizophrenia by experienced doctors (42 cases), patients with intermediate forms of schizophrenia and manic depression (4 cases), and patients with manic depression (15 cases). ), Patients with personality disorder (4 cases), patients who received valproic acid after brain surgery (9 cases), healthy subjects (20 cases), and patients with multiple sclerosis (14 cases).

It should be noted that multiple sclerosis is a disease in which HERV-W (originally called MSRV) was first isolated, although clinical similarity with schizophrenia was not observed in disease symptoms. In addition, valproic acid is a drug that is often administered during the excitement phase of schizophrenia, and is known to have an inhibitory action on deacetylase. Valproic acid may also be administered as an anticonvulsant to patients who have undergone brain surgery, such as traffic trauma or brain tumor removal. Therefore, taking into account the possibility that the administration of valproic acid activates HERV-W, which is potentially present in the genome, and expresses the syncytin-1 protein, undergoes brain surgery for traffic trauma, brain tumor removal, etc., and administers valproic acid Patients were also added to the subjects.

Table 1 shows the detection results of anti-scincytin-1 antibody in each subject. In Table 1, “S” indicates a patient with schizophrenia, “SM” indicates a patient that is intermediate between schizophrenia and manic depression, “M” indicates a patient with manic depression, and “PD” Indicates a patient with personality disorder and “MS” indicates a patient with multiple sclerosis. “Anti-syncytin-1 antibody (−)” indicates the number of subjects in which anti-syncytin-1 antibody was not detected, and “anti-syncytin-1 antibody (+)” indicates subjects in which anti-syncytin-1 antibody was detected. Indicates the number of Here, the reason for targeting patients after brain surgery is that, after brain surgery, a histone deacetylation inhibitor (HDAC inhibitor) is usually administered to prevent postoperative convulsions. The syncytin-1 gene is present in all human genomes, and its expression (translation into protein) is suppressed by the action of HDAC, but its expression may be induced by administration of an HDAC inhibitor. Because it was thought that there was.

As a result, it was revealed that anti-scincytin-1 antibody is present in the blood of a considerable number of patients with schizophrenia-related diseases.

Of the schizophrenic patients (S), 7 were valproic acid patients. Also, anti-scincytin-1 antibody was detected in 1 of these 7 patients (14.2%). On the other hand, it is clear that anti-syncytin-1 antibody is not present in the blood of patients who received valproic acid after brain surgery (these patients did not suffer from schizophrenia-related diseases) It became. This indicates that the presence of anti-syncytin-1 antibody in the blood of patients with schizophrenia-related diseases is not due to the administration of valproic acid.

In addition, anti-syncytin-1 antibody was not detected in the blood of healthy subjects and patients with multiple sclerosis.

The above results indicate that patients with anti-syncytin-1 antibody can be objectively determined to have schizophrenia-related diseases.

[Experiment 3]
(Epitope mapping of anti-syncytin-1 antibody)
The epitope of anti-syncytin-1 antibody detected from a patient with schizophrenia-related disease was examined by epitope mapping.

Specifically, based on the amino acid sequence of the 538 amino acid syncytin-1 protein, a total of 264 peptides consisting of 12 amino acids shifted by 2 amino acids were synthesized and immobilized on a cellulose membrane. Subsequently, this cellulose membrane was reacted with serum from a patient with a schizophrenia-related disease, and anti-syncytin-1 antibody was detected using an HRP-labeled anti-human IgG antibody.

FIG. 1 is a graph showing typical results of epitope mapping. FIG. 1 shows the results of using sera from seven patients with schizophrenia-related diseases assigned with identification numbers S1 to 7. FIG. 1 also shows the results of using a polyclonal antibody against a peptide consisting of the amino acid sequence of amino acids 33 to 312 of SEQ ID NO: 1 as a control instead of patient serum. In the graph of FIG. 1, the vertical axis represents the amount (relative value) of the detected anti-scincytin-1 antibody.

As a result, it was considered that the epitopes commonly recognized by the anti-scincytin-1 antibodies of 7 patients were present in the three shaded portions in FIG. As a result, a peptide consisting of the 30th to 58th amino acid sequence of the amino acid sequence shown in SEQ ID NO: 1, a peptide consisting of the 193th to 221st amino acid sequence of the amino acid sequence shown in SEQ ID NO: 1, It shows that a peptide consisting of the amino acid sequence of 493 to 521 of the described amino acid sequence can be used as an antigen for detecting anti-scincytin-1 antibody.

[Experimental Example 4]
(Comparison of Western blotting and ELISA)
Anti-syncytin-1 antibody in the serum of the test subject was detected by Western blotting and ELISA, and the detection sensitivity was compared.

As subjects, patients diagnosed as schizophrenia by experienced doctors (46 cases) and manic-depressed patients (25 cases) were used. For comparison, healthy subjects (32 cases) and multiple sclerosis patients (13 cases) were used.

Table 2 below shows the gender ratio and age distribution of each subject. In Table 2, “S” indicates a schizophrenic patient, “M” indicates a manic-depressed patient, and “MS” indicates a patient with multiple sclerosis. As a result, as shown in Table 2 below, it was confirmed that there was no significant difference in the sex ratio and age distribution of each subject. However, there was a difference in age distribution among patients with multiple sclerosis.

<Western blotting method>
Using the syncytin-1 protein purified in Experimental Example 1, anti-syncytin-1 antibody in the serum of each subject was detected in the same manner as in Experimental Example 2.

<< ELISA method >>
First, the syncytin-1 protein purified in Experimental Example 1 was immobilized on a 96-well plate. Subsequently, the serum derived from the subject was diluted to 1/100 and added to each of the wells to cause a reaction. Subsequently, an HRP-labeled anti-human IgG antibody was reacted, and further an HRP substrate was reacted to detect an anti-cincytin-1 antibody.

Table 2 below shows the number of subjects in which anti-syncytin-1 antibody was detected and the percentage (%) of subjects in which anti-syncytin-1 antibody was detected.

As a result, it was revealed that the ELISA method can detect the anti-syncytin-1 antibody with higher sensitivity than the Western blotting method. This result further supports the higher proportion of anti-scincytin-1 antibody detected in the serum of patients with schizophrenia-related diseases than in healthy individuals.

[Experimental Example 5]
(Examination of antigenic peptides in ELISA)
The anti-sincitin-1 antibody in the serum of the subject was detected by the ELISA method in the same manner as the ELISA method of Experimental Example 4 except that a plate on which a partial peptide of the syncytin-1 protein was immobilized was used, and the detection sensitivity was increased. Compared. Peptides were used at a concentration of 10 μg / mL and serum was used at a 100-fold dilution.

The subjects used were 8 patients who were diagnosed with schizophrenia by experienced doctors. In addition, healthy subjects (3 cases) were used for comparison.

In addition, peptides shown in Table 3 below were used as partial peptides of the syncytin-1 protein.

FIG. 2 is a graph showing the results of detection of anti-syncytin-1 antibody. In FIG. 2, “C1” to “C3” indicate the results of the serum of healthy subjects. In addition, “S1” to “S8” indicate the results of sera from patients with schizophrenia, respectively. “OD (A450)” means absorbance at a wavelength of 450 nm.

As a result, it was revealed that particularly high detection sensitivity can be obtained by immobilizing peptide # 8 (SEQ ID NO: 9) as a partial peptide of the syncytin-1 protein and performing ELISA. It was also found that the detection sensitivity of the anti-scincytin-1 antibody is reduced when other peptides are mixed with peptide # 8.

[Experimental Example 6]
(Inhibition of ELISA reaction by peptide)
Anti-syncytin-1 antibody was detected in the serum of the subject by ELISA using a plate on which peptide # 8 (SEQ ID NO: 9) was immobilized. In this process, partial peptides of various syncytin-1 proteins were allowed to coexist and the inhibitory effect on the ELISA reaction was examined.

As partial peptides of the syncytin-1 protein, peptide # 1 (SEQ ID NO: 2), peptide # 3 (SEQ ID NO: 4) prepared at final concentrations of 0, 0.01, 0.1, 1 and 10 μg / mL, respectively, Peptide # 5 (SEQ ID NO: 6), peptide # 7 (SEQ ID NO: 8) or peptide # 8 (SEQ ID NO: 9) was used.

Also, as subjects, patients diagnosed as schizophrenia by experienced doctors (2 cases) and manic-depressed patients (2 cases) were used. In addition, healthy subjects (one example) were used for comparison.

FIGS. 3 (a) to 3 (e) are graphs showing the results of detection of anti-syncytin-1 antibody. In FIGS. 3 (a) to 3 (e), “C1” indicates the result of the serum of a healthy person. Further, “S1” and “S2” indicate the results of sera from patients with schizophrenia, respectively. In addition, “M1” and “M2” indicate the results of serum of manic-depressive patients, respectively. “OD (A450)” means absorbance at a wavelength of 450 nm.

As a result, it was confirmed that anti-syncytin-1 antibody was not detected in the serum of healthy subjects, and anti-syncytin-1 antibody was detected in the serum of patients with schizophrenia-related diseases. In addition, in the ELISA method using a plate on which peptide # 8 was immobilized, it was confirmed that detection of anti-scincytin-1 antibody was inhibited only when peptide # 8 coexists.

According to the present invention, a technique capable of objectively diagnosing schizophrenia-related diseases can be provided.

Claims (8)

A marker for diagnosing schizophrenia-related diseases, consisting of anti-syncytin-1 antibody. A kit for diagnosing schizophrenia-related diseases, comprising syncytin-1 protein or a fragment thereof. The diagnostic kit for schizophrenia-related disease according to claim 2, further comprising a specific binding substance for a human antibody. A fragment of a syncytin-1 protein, wherein the fragment is a peptide consisting of the amino acid sequence set forth in SEQ ID NO: 9, or one or several amino acids are deleted or substituted in the amino acid sequence set forth in SEQ ID NO: 9 Alternatively, the kit for diagnosing schizophrenia-related disease according to claim 2 or 3, which is a peptide comprising an added amino acid sequence and recognized by an anti-scincytin-1 antibody. A method for collecting data for serologically identifying the possibility that a subject is suffering from schizophrenia-related disease, wherein whether anti-scincytin-1 antibody is present in blood from the subject And the presence or absence of the antibody is data for serologically identifying the possibility that the subject has a schizophrenia-related disease. The method according to claim 5, wherein the step of detecting whether or not anti-syncytin-1 antibody is present is performed by ELISA. A step of detecting whether or not an anti-scincytin-1 antibody is present in blood derived from the subject, and if the antibody is present, the subject may suffer from schizophrenia-related disease A method for testing whether or not the subject suffers from schizophrenia-related disease by comparing with a criterion that in the absence of the antibody, the subject does not suffer from schizophrenia-related disease. The method according to claim 7, wherein the step of detecting whether or not anti-syncytin-1 antibody is present is performed by an ELISA method.

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