CN107345970A - A kind of peripheral blood biomarker available for Schizophrenia diagnosis - Google Patents
A kind of peripheral blood biomarker available for Schizophrenia diagnosis Download PDFInfo
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- CN107345970A CN107345970A CN201710596835.1A CN201710596835A CN107345970A CN 107345970 A CN107345970 A CN 107345970A CN 201710596835 A CN201710596835 A CN 201710596835A CN 107345970 A CN107345970 A CN 107345970A
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/30—Psychoses; Psychiatry
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Abstract
The present invention relates to a kind of peripheral blood biomarker available for Schizophrenia diagnosis, and its for diagnosing the purposes of Schizophrenia.Specifically, first episode schizophrenia is diagnosed by detecting the horizontal of the free IL 15R α in peripheral blood.
Description
Technical field
This disclosure relates to the diagnosis of mental illness objective diagnosis, the schizophrenia course of disease order of severity, Schizophrenia
Antidiastole, objective biomarker with bipolar disorder, peripheral blood biomarker.
Background technology
Schizophrenia (Schizophrenia) is a kind of common mental illness, and the illness rate in global population is
0.3%-0.7%.The more onsets of schizophrenia in person between twenty and fifty, often have many obstacles such as perception, thinking, emotion, behavior and
Cerebration it is uncoordinated, have a strong impact on the body function and quality of life of patient.Although some patients can be by treating
With rehabilitation, but it is most of can undergo prolonged and repeated breaking-out, therefore schizophrenia is not only the disease of individual, while is also one
The social concern that can not be despised, obvious financial burden can all be caused to its family, healthcare system and entire society.
At present, clinically to schizoid diagnosis mainly according to the detailed history and mental symptom of patient, then join
Its age of onset, stadium, course of disease etc. are examined to do comprehensive descision, therefore generally one mistake for depending on doctor's subjective experience
Journey, diagnostic result usually vary with each individual.In order that schizoid diagnosis more objectifies, the uniformity and standard of diagnosis are improved
Exactness, in recent years, researcher all over the world are directed to finding schizoid biomarker always, establish effective
Detection method.Biomarker refers to certain spy in the generic physiological for being available for objective determination and evaluation or pathology or therapeutic process
The biochemical indicator of sign property, the process in the biological process being presently in by the way that body can be known to its measure.Biology mark
The chemical nature of will thing can be DNA, RNA, albumen or metabolin, typically be obtained from body fluid.Biomarker is applied to essence
Refreshing Split disease, uncertain human factor in Current Diagnostic can be effectively aided in, reduce mistake/misdiagnosis rate and contribute to direction of medication usage
And rehabilitation course.
Therefore, the biomarker that can be used for diagnosis Schizophrenia is badly in need of in this area, and the mark should be reliable,
Should also possess good sensitivity and specificity.
Psychotic symptoms are schizoid significant symptoms, and bipolar disorder patient is in manic and paralepsy
Period can also have these symptoms, such as illusion and vain hope.And the treatment method of both greatly differs from each other, schizophrenia is main
Antipsychotics is used, and bipolar disorder is mainly treated using mood stabilizers.On the other hand, schizophreniac
Often there is negative symptoms, i.e. speaking scarcely,taciturn, behavior is reduced, dull spirit etc., and this performance with severe depression is like but treating
Method is entirely different, for depression, mainly using antidepressants.Error diagnosis will cause patient effectively to treat, together
When also will the greatly treatment confidence of strike patient and the trust to doctor hospital, reduce compliance, further result in various serious
Consequence, therefore there is an urgent need to carry out antidiastole to schizophrenia and above two disease.
Detect that schizoid biomarker has detection sensitivity and the degree of accuracy is not high at present, still without being capable of area
Divide the detection method of schizophrenia and Bipolar Disorder and depression.
IL-15 is one of interleukin family, belongs to 4 α supercoil cell factor superfamilies, its acceptor is by α, β and γ subunit
The tripolymer of composition, α subunits can specific combination IL-15.IL-15/IL-15R α are distributed widely in various histocytes, remove
It can promote that the immune cell propagations such as T cell, NK cells, BMDC break up and function is ripe outer, can also adjust various
Nonimmune cell function, as promoted fibroblast, epithelial cell, myocyte, liver cell, keratinocyte, adipocyte etc.
Propagation and differentiation, suppress apoptosis.
The present inventor is by detecting the IL-15R α of dissociating in the serum in common psychiatric patient and control crowd level
Provide the solution of above-mentioned technical problem.
Present disclose provides an objective measure for being used to diagnose Schizophrenia, that is, detect in peripheral blood
Free IL-15R α level.There are following outstanding advantages and feature：
1. the diagnosis of pair Schizophrenia has higher specificity and sensitivity.
2. belonging to hematological index, can conveniently obtain.
3. single index detection method, an index need to be only surveyed, it is convenient to promote the use of in the future.Also other detections can conveniently be combined
Mode draws more reliable result.
4. the morbidity order of severity that can be to Schizophrenia is monitored.
5. can be made a distinction to Schizophrenia and bipolar disorder and depression or antidiastole, it is
Precision treatment lays the foundation.
The content of the invention
On the one hand, this disclosure relates to which IL15R α are being prepared for diagnosing in the kit of first episode schizophrenia
Purposes.
On the one hand, this disclosure relates to which IL15R α are preparing the kit for diagnosing first episode schizophrenia prognosis
In purposes.
On the other hand, this disclosure relates to which IL15R α are being prepared for distinguishing first episode schizophrenia and Bipolar
Purposes in the kit of impaired patients.
On the other hand, this disclosure relates to which IL15R α are being prepared for distinguishing first episode schizophrenia and depression trouble
Purposes in the kit of person.
On the one hand, this disclosure relates to which the reagent for detecting IL15R α is being prepared for diagnosing first episode schizophrenia
Purposes in kit.
On the one hand, this disclosure relates to which the reagent for detecting IL15R α is pre- for diagnosing first episode schizophrenia in preparation
The purposes in kit afterwards.
On the other hand, this disclosure relates to which the reagent for detecting IL15R α is being prepared for distinguishing first episode schizophrenia
With the purposes in the kit of bipolar disorder patient.
On the other hand, this disclosure relates to which the reagent for detecting IL15R α is being prepared for distinguishing first episode schizophrenia
With the purposes in the kit of patients with depression.
On the one hand, this disclosure relates to judge the method for Schizophrenia risk, IL15R α wherein in peripheral blood
Content declines compared to normal control values, and risk of the instruction with Schizophrenia rises.
On the one hand, this disclosure relates to distinguish first episode schizophrenia and the method for patients with depression, wherein IL15R
α content declines risk of the instruction with Schizophrenia compared to normal control values and risen.
On the one hand, this disclosure relates to the method for distinguishing first episode schizophrenia and bipolar disorder patient, its
Middle IL15R α content declines risk of the instruction with Schizophrenia compared to normal control values and risen.
On the one hand, this disclosure relates to distinguish first episode schizophrenia and the method for patients with depression, wherein IL15R
α content compared to normal control values there was no significant difference instruction with depression risk rise.
On the one hand, this disclosure relates to the method for distinguishing first episode schizophrenia and bipolar disorder patient, its
Middle IL15R α content compared to normal control values there was no significant difference instruction with bipolar disorder risk rise.
According to any preceding aspect, the reagent of the detection IL15R α can be IL15 or its antibody, IL15R α part
Or its antibody, IL15R α antibody, colour reagent, luminous sign thing, dyestuff, fluorescent marker etc..
According to any preceding aspect, this disclosure relates to detect the content of IL15R α in peripheral blood, blood plasma, serum.
According to any preceding aspect, the disclosure by ELISA, western-blot, mass spectral analysis, chromatography, acceptor-
Part is affine, and experiment etc. detects IL15R α content.
On the one hand, this disclosure relates to for diagnosing Schizophrenia, bipolar disorder or the reagent of depression
Reagent containing detection IL15R alpha contents in box, wherein kit, optionally, the kit can contain IL15 or it is anti-
Body, IL15R α part or its antibody, IL15R α antibody, colour reagent, luminous sign thing, dyestuff, fluorescent marker etc..
On the other hand, kit of the invention is also containing other detection schizophrenia, bipolar disorder or depressions
The marker detection reagent of disease.
Brief description of the drawings
The preferred embodiment of the present invention described with reference to the accompanying drawings, in accompanying drawing：
Fig. 1 is soluble IL15R α in normal control, the super people at highest risk of essence point, in first episode schizophrenia crowd
Serum content.*, P<0.05；* * *, P<0.0001.
Fig. 2 is soluble IL15R α in normal control, first episode schizophrenia, the blood in two-way disturbance of emotion crowd
Clear content.*, P<0.05；* * *, P<0.0001.
Fig. 3 is soluble IL15R α in normal control, first episode schizophrenia, and the serum in depression crowd contains
Amount.*, P<0.05；* * *, P<0.0001.
Embodiment
It can include expression and purification IL15R using the IL15R α kits prepared for diagnosing first episode schizophrenia
α polypeptides, mutant, fragment, epitope, fusion protein etc., then prepare corresponding antibody or antigen-binding fragment and be used to examine
Part corresponding to survey or antigen, IL15R α polypeptides, mutant, fragment, epitope, fusion protein can also be used in kit
It is middle to be used as positive control or competitive binding albumen etc..
It can include expression and purification using the IL15R α kits prepared for diagnosing first episode schizophrenia prognosis
IL15R α polypeptides, mutant, fragment, epitope, fusion protein etc., then prepare corresponding antibody or antigen-binding fragment and use
In part corresponding to detection or antigen, IL15R α polypeptides, mutant, fragment, epitope, fusion protein can also be used to try
Positive control or competitive binding albumen etc. are used as in agent box.
Being prepared using IL15R α can for distinguishing the kit of first episode schizophrenia and bipolar disorder patient
With including expression and purification IL15R α polypeptides, mutant, fragment, epitope, fusion protein etc., then prepare corresponding antibody or
Antigen-binding fragment is used to detect corresponding part or antigen, can also use IL15R α polypeptides, mutant, fragment, antigen table
Position, fusion protein are used as positive control or competitive binding albumen etc. in kit.
It can be included using the IL15R α kits prepared for distinguishing first episode schizophrenia and patients with depression
Expression and purification IL15R α polypeptides, mutant, fragment, epitope, fusion protein etc., then prepare corresponding antibody or antigen knot
Close fragment to be used to detect corresponding part or antigen, IL15R α polypeptides, mutant, fragment, epitope, fusion can also be used
Albumen is used as positive control or competitive binding albumen etc. in kit.
Detection IL15R α reagent can include IL15 or its antibody, IL15R α part or its antibody, and IL15R α's is anti-
Body, colour reagent, luminous sign thing, dyestuff, fluorescent marker etc..It will be understood by those skilled in the art that the detection periphery of the disclosure
The horizontal of free IL-15R α in blood can also use western-blot, matter with the ELISA kit of commodity in use
Compose analysis, chromatography, receptor-ligand is affine experiment etc. detects IL15R α content.According to specific experiment condition and needs, sheet
Art personnel can know how to select conventional detection means, as long as the means can detect the free IL- in peripheral blood
15R α level.The disclosure has used the commercialization solubility IL-15R α ELISA detection kits of market sale to periphery
IL15R α level is detected in blood, can relatively be judged according to IL15R α horizontal height.People in the art
Member is appreciated that other detection methods, such as western-blot can be according to the thickness, the depth, luminous intensity of test strip
Be compared Deng the level to IL15R α, mass spectral analysis can carry out quantitative comparison, chromatography can be according in peripheral blood
Comparision contents corresponding to the progress such as IL15R α characteristic peak area, experiment that receptors ligand is affine can match somebody with somebody style using IL15R α
IL15R α level is detected as specific affinity ligand such as IL15 or IL15R α antibody.
Those skilled in the art are it is also understood that levels of the detection IL15R α in peripheral blood can detect whole blood, blood
The level of slurry or the IL15R α in serum, the level of IL15R α in peripheral blood whole blood, Huo Zhefen can be detected as the case may be
From the level that IL15R α are detected after the level that IL15R α are detected after blood plasma, or separation serum.
According to disclosed method, when use existing psychology measuring scale or mental illness Diagnostic Scale or handbook etc.
When can not judge, more objective basis for estimation can be provided by detecting the level of IL15R α in peripheral blood.For example, in peripheral blood
IL15R α content declines compared to normal control values, and risk of the instruction with Schizophrenia rises.
According to this disclosure relates to distinguish first episode schizophrenia and the method for patients with depression, wherein IL15R α's contains
Amount declines possibility increase of the instruction with Schizophrenia compared to normal control values.
According to the differentiation first episode schizophrenia of the disclosure and the method for bipolar disorder patient, wherein IL15R α
Content compared to normal control values decline instruction with Schizophrenia possibility increase.
According to the content of the method, wherein IL15R α of the differentiation first episode schizophrenia and patients with depression of the disclosure
Compared to normal control values there was no significant difference instruction with depression possibility increase.
According to the differentiation first episode schizophrenia of the disclosure and the method for bipolar disorder patient, wherein IL15R α
Content compared to normal control values there was no significant difference instruction with bipolar disorder possibility.
The disclosure is further related to for diagnosing schizophrenia, bipolar disorder or the kit of depression, wherein reagent
Reagent containing detection IL15R alpha contents in box, optionally, the kit can contain IL15 or its antibody, and IL15R α's matches somebody with somebody
Body or its antibody, IL15R α antibody, colour reagent, luminous sign thing, dyestuff, fluorescent marker etc..
On the other hand, kit of the invention is also containing other detection schizophrenia, bipolar disorder or depressions
The marker detection reagent of disease.
Kit of the invention can simultaneously comprising detection IL15R alpha contents reagent and it is schizoid other
Biomarker detection reagent, the detection reagent of the schizoid other biological mark for example detect a) 3- hydroxyls fourth
Acid or its analog；B) glyceric acid or its analog；And c) one or more reagents of cysteine or its analog；Also example
The reagent of microRNA molecule mark is such as detected, the blood microRNA molecule mark is has-miR-132, miR-
132 mature sequences are：UAACAGUCUACAGCCAUGGUCG；The lncRNA marks for schizophrenia diagnosis are for example detected again
The detection reagent of thing detects detection reagent of circRNA marks of schizophrenia diagnosis etc..
The reagent and the other biological mark of depression that kit such as the present invention can be simultaneously comprising detection IL15R alpha contents
Will quality testing test agent, the detection reagent of the other biological mark of the depression for example detect BDNF,
Cortisol, EGF, myeloperoxidase, prolactin, phylaxin, soluble tumor necrosis factor α receptor II types
Horizontal reagent；Also for example detect the reagent of microRNA molecule mark and detect the lncRNA marks for Diagnosis of Depression
The detection reagent of thing detects detection reagent of circRNA marks of Diagnosis of Depression etc..
Kit such as the present invention can include other for the reagent and bipolar disorder for detecting IL15R alpha contents simultaneously
Biomarker detection reagent.
By being applied in combination with the detection reagent of other biological mark, that the kit of the disclosure can provide is more objective,
Accurate diagnostic result.
Schizophrenia superelevation danger or essence point superelevation danger described in the disclosure refer to schizophreniac before First episode
Residing schizophrenia forerunner's phase (prodromal stage), the crowd for having prodromal stage performance develop into schizoid
Possibility is larger, and this kind of crowd is currently referred to as super people at highest risk (ultra high risk for psychosis, UHR).
Schizophrenia described in the disclosure refer to patient be in phrenoplegia phase first, non-medication or morbidity with
Continuously with antipsychotic drug to be no more than the state of 1 month.
Embodiment
Method：
All objects for participating in experiment voluntarily sign informed consent form, and can comply with research approach；Dextro manuality, the age is 16
Between~40 years old.Age, sex, education degree matching, no difference of science of statistics between each group.
The one of situations below occur need to exclude outside this research：
Gestation, women breast-feeding their children；
It is on wires, gets excited, loner；
There is serious conamen person；
Head injury history, the loss of consciousness are super after an hour；
With severe physical disease patient or organic brain function disease, hence it is evident that influence mental illness curer；
Exclude secondary depressive symptom (physical disease, medicine or other reasons)；
Receive electric spasm (MECT) curer in recent 3 months.
Schizophrenia group inclusion criteria：Meet Americanism medical diagnosis on disease and statistic handbook fourth edition (DSM-IV)
Schizophrenia diagnosis standard；Age of onset more than 15 years old, in the phrenoplegia phase first, connect since non-medication or morbidity
Continuous antipsychotic drug is no more than 1 month.
Schizophrenia superelevation danger group inclusion criteria：Neuropsychosis risk integrative sign fixed pattern interview (Structured
Interview for Psychosis-risk Syndromes, SIPS) examination meet mental disease risk integrative sign diagnosis.
Two-way disturbance of emotion inclusion criteria：Meet Americanism medical diagnosis on disease and pair of statistic handbook fourth edition (DSM-IV)
Phase disturbance of emotion diagnostic criteria.
Depression inclusion criteria：Meet Americanism medical diagnosis on disease and the depression of statistic handbook fourth edition (DSM-IV) is examined
Disconnected standard.
Healthy control group：The Healthy People to match with above-mentioned each group age, sex, schooling.
According to the Ethic review experimental program passed through, and diagnostic criteria, normal control population, starting spirit are filtered out
Split disease, super people at highest risk, bipolar disorder and depression crowd.Subject's number of cases：First episode schizophrenia 70,
Depressive patient 98, bipolar patients 86, essence divide superelevation to endanger 64, health 97.Totally 395.5 milliliters of peripheral blood is extracted, often
Temperature is lower to be promoted to solidify in solidifying pipe, and 500g is centrifuged 10 minutes, separates upper serum, and is dispensed at once, is stored in -80 DEG C of ultralow temperature ices
Case, it is standby.
The commercialization solubility IL-15R α ELISA detection kits of market sale are bought, according to operation instruction, every quilt
Examination takes 100ul serum to be detected.The kit that this experiment uses is the magnificent biological human interleukin 15 receptor alpha subunit in Wuhan
(IL15RA) ELISA kit (article No. CSB-EL011594HU).
Embodiment 1：The diagnosis of Schizophrenia and the judgement of the Schizophrenia illness order of severity
The serum of schizophrenia crowd, the super people at highest risk of essence point and normal healthy controls crowd are taken, with commercialization solubility IL-
Soluble IL15R α concentration in 15R α ELISA detection kits detection serum.Using the statistics between t test and judge difference groups
Learn difference.As a result as shown in fig. 1, the soluble IL15R α concentration of first episode schizophrenia is minimum, and and normal healthy controls
Group has pole significant difference, and super people at highest risk shows good dose-effect relationship between normal person and patient.The result table
It is bright to be suffered from using soluble IL15R α Concentration Testings to carry out the diagnosis of Schizophrenia and Schizophrenia
The judgement of the sick order of severity.
Embodiment 2：The diagnosis of Schizophrenia and the discriminating of Schizophrenia and bipolar disorder are examined
It is disconnected
The serum of Schizophrenia crowd, bipolar disorder crowd and normal healthy controls crowd are taken, can with commercialization
Soluble IL15R α concentration in dissolubility IL-15R α ELISA detection kits detection serum.Using the different groups of t test and judges
Between significant difference.As a result as shown in Figure 2, the soluble IL15R α concentration of first episode schizophrenia is minimum, and with
Healthy control group has pole significant difference, and bipolar disorder crowd is similar with healthy control group and suffers from Schizophrenia
Significant difference be present in the soluble IL15R α concentration of person.The result shows using soluble IL15R α Concentration Testings to enter
The diagnosis of row Schizophrenia and the antidiastole of Schizophrenia and bipolar disorder.
Embodiment 3：The antidiastole of the diagnosis of Schizophrenia and Schizophrenia and depression
The serum of Schizophrenia crowd, depression crowd and normal healthy controls crowd are taken, with commercialization solubility IL-
Soluble IL15R α concentration in 15R α ELISA detection kits detection serum.Using the statistics between t test and judge difference groups
Learn difference.As a result as shown in Figure 2, the soluble IL15R α concentration of first episode schizophrenia is minimum, and and normal healthy controls
Group has a pole significant difference, and depression crowd is similar with healthy control group and solubility with first episode schizophrenia
Significant difference be present in IL15R α concentration.The result shows that starting spirit can be carried out using soluble IL15R α Concentration Testings
The antidiastole of the diagnosis of Split disease and Schizophrenia and depression.
Claims (10)
1.IL15R α are preparing the purposes in being used to diagnose the kit of first episode schizophrenia.
2.IL15R α are preparing the purposes in being used to diagnose the kit of first episode schizophrenia prognosis.
3.IL15R α are preparing the use in being used to distinguish the kit of first episode schizophrenia and bipolar disorder patient
On the way.
4.IL15R α are preparing the purposes in being used to distinguish the kit of first episode schizophrenia and patients with depression.
5. detection IL15R α reagent is preparing the purposes in being used to diagnose the kit of first episode schizophrenia.
6. detection IL15R α reagent is preparing the purposes in being used to diagnose the kit of first episode schizophrenia prognosis.
7. detection IL15R α reagent is preparing the examination for distinguishing first episode schizophrenia and bipolar disorder patient
Purposes in agent box.
8. detection IL15R α reagent is being prepared for distinguishing in the kit of first episode schizophrenia and patients with depression
Purposes.
9. according to claim 5-8 purposes, wherein the reagent of the detection IL15R α is selected from：
IL15R α part or its antibody, IL15R α antibody, colour reagent, luminous sign thing, dyestuff, fluorescent marker.
10. the kit for diagnosing Schizophrenia, the reagent containing detection IL15R alpha contents wherein in kit, appoint
Selection of land, the kit can contain IL15 or its antibody, IL15R α part or its antibody, IL15R α antibody, colour developing examination
Agent, luminous sign thing, dyestuff, fluorescent marker etc., it is preferable that the kit is also containing other starting schizophrenias of detection
The detection reagent of the mark of disease, bipolar disorder or depression.
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| CN113151443B (en) * | 2021-04-16 | 2022-07-01 | 中央民族大学 | Cytokine combined analysis as schizophrenia marker and application thereof |
| CN113215249A (en) * | 2021-06-29 | 2021-08-06 | 中国人民解放军军事科学院军事医学研究院 | IL-26 for the identification and diagnosis of anxious depression |
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