CN112557283A - Diagnosis and treatment immune marker for recurrent pregnancy loss diseases and application thereof - Google Patents
Diagnosis and treatment immune marker for recurrent pregnancy loss diseases and application thereof Download PDFInfo
- Publication number
- CN112557283A CN112557283A CN202011338622.7A CN202011338622A CN112557283A CN 112557283 A CN112557283 A CN 112557283A CN 202011338622 A CN202011338622 A CN 202011338622A CN 112557283 A CN112557283 A CN 112557283A
- Authority
- CN
- China
- Prior art keywords
- cells
- cell
- pregnancy loss
- immune
- recurrent pregnancy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010055690 Foetal death Diseases 0.000 title claims abstract description 61
- 230000000306 recurrent effect Effects 0.000 title claims abstract description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 19
- 238000003745 diagnosis Methods 0.000 title claims abstract description 8
- 239000003550 marker Substances 0.000 title claims description 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 45
- 230000002093 peripheral effect Effects 0.000 claims abstract description 9
- 210000002443 helper t lymphocyte Anatomy 0.000 claims abstract description 8
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 claims abstract description 7
- 210000000822 natural killer cell Anatomy 0.000 claims abstract description 7
- 239000012636 effector Substances 0.000 claims abstract description 6
- 210000001939 mature NK cell Anatomy 0.000 claims abstract description 6
- 210000003289 regulatory T cell Anatomy 0.000 claims abstract description 5
- 230000035935 pregnancy Effects 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 claims description 2
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 claims description 2
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 claims description 2
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 claims description 2
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 claims description 2
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 2
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 claims description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000000090 biomarker Substances 0.000 claims 1
- 210000002865 immune cell Anatomy 0.000 abstract description 16
- 238000001514 detection method Methods 0.000 abstract description 6
- 208000000995 spontaneous abortion Diseases 0.000 abstract description 5
- 206010000234 Abortion spontaneous Diseases 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 4
- 239000000427 antigen Substances 0.000 abstract description 2
- 102000036639 antigens Human genes 0.000 abstract description 2
- 108091007433 antigens Proteins 0.000 abstract description 2
- 238000011161 development Methods 0.000 abstract description 2
- 210000000987 immune system Anatomy 0.000 abstract description 2
- 208000015994 miscarriage Diseases 0.000 abstract description 2
- 230000008775 paternal effect Effects 0.000 abstract description 2
- 210000005259 peripheral blood Anatomy 0.000 description 8
- 239000011886 peripheral blood Substances 0.000 description 8
- 230000035558 fertility Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 208000031404 Chromosome Aberrations Diseases 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 206010000210 abortion Diseases 0.000 description 3
- 231100000176 abortion Toxicity 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000027758 ovulation cycle Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- 230000003331 prothrombotic effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000011870 unpaired t-test Methods 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 206010067477 Cytogenetic abnormality Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000003509 immature nk cell Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000036266 weeks of gestation Effects 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N2015/1402—Data analysis by thresholding or gating operations performed on the acquired signals or stored data
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pathology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Dispersion Chemistry (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention belongs to the technical field of biomedical detection, and particularly relates to a group of diagnosis and treatment immune markers for diseases caused by repeated pregnancy loss and application thereof. The immune markers include: initial CD4+T cell, central memory CD4+T cell, effector memory CD4+T cell, terminally differentiated CD4+T cells, Treg cells, peripheral helper T cells, central CD8+T cell, terminally differentiated CD8+T-cell, non-active phase specific terminally differentiated CD8+T cell, depleted CD8+At least one of T cells, T NK cells, mature NK cells, immature NK/mature NK ratio, γ δ T cells. These 15 subtypes of immune cells associated with recurrent pregnancy loss suggest that the immune system of women with recurrent pregnancy loss is under-tolerated and therefore unable to tolerate foetuses carrying paternal antigens leading to the development of miscarriage.
Description
Technical Field
The invention belongs to the technical field of biomedical detection, and particularly relates to a group of diagnosis and treatment immune markers for diseases caused by repeated pregnancy loss and application thereof.
Background
Recurrent pregnancy loss refers to the loss of pregnancy occurring 2 or more times before 20 weeks of gestation, the incidence rate of which in women of childbearing age is 1% -5%, and the risk of miscarriage of patients of this type of pregnancy increases with the number of miscarriages. The causes of the disease mainly include chromosome abnormality, anatomical structure abnormality, endocrine factors, autoimmune factors, thrombosis liability, infection, environmental factors, psychology and other factors. And bothers clinicians and patients: about 50% of women still do not find the cause of recurrent pregnancy loss after excluding the above known causes, which is also called recurrent pregnancy loss of unknown cause. More and more studies are currently underway to show that maternal immune imbalance may be the major cause of recurrent pregnancy loss of unknown origin, accounting for over 60%.
During the menstrual cycle and gestation, immune cells (NK cells, T cells and γ δ T cells) are dynamically changed as the hormone levels change. It has been shown that the abnormal number and/or function of a single immune cell or a certain kind of immune cell subsets in the peripheral blood of a mother are closely related to the occurrence of recurrent pregnancy loss, but the systematic and accurate detection and screening of multiple immune cell subsets of the mother are lacked. Thus, there is a lack of assessment of the number and function of maternal whole immune cell subsets.
The current examinations for patients with recurrent pregnancy loss of unknown origin mainly include basic physical examination, ultrasound examination and invasive endometrial pathology, which cannot assess the immune status of the mother and lack specific immune markers. Nevertheless, patients with recurrent pregnancy loss still have a strong desire to detect an indicator of immunity or monitor an assessment of an indicator of immunotherapy effectiveness.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a group of diagnosis and treatment immune markers for recurrent pregnancy loss diseases and application thereof, and aims to solve part of problems in the prior art or at least alleviate part of problems in the prior art.
The invention mainly adopts multi-parameter flow cytometry to simultaneously detect 63 immune cell subtypes in peripheral blood of non-pregnant women, born women and women with recurrent pregnancy loss (50 cases in each group), and through multi-group unpaired t test, immune indexes of the non-pregnant women and the women with recurrent pregnancy loss and the born women and the women with recurrent pregnancy loss which are simultaneously different are selected as immune cell subtypes related to recurrent pregnancy loss.
The invention is realized by that a group of immune markers for diagnosing and treating recurrent pregnancy loss diseases comprises initial CD4+T cell, central memory CD4+T cell, effector memory CD4+T cell, terminally differentiated CD4+T cells, Treg cells, peripheral helper T cells, central memory CD8+T cell, terminally differentiated CD8+T-cell, non-active phase specific terminally differentiated CD8+T cell, depleted CD8+At least one of T cells, T NK cells, mature NK cells, immature NK/mature NK ratio, γ δ T cells.
The invention also discloses application of the group of diagnosis and treatment immune markers for the recurrent pregnancy loss diseases in preparation of a reagent or a kit for diagnosing the recurrent pregnancy loss diseases.
The present invention also discloses a reagent or a kit for diagnosing and treating recurrent pregnancy loss diseases, which comprises a reagent for detecting an immune-related molecule expressed by the immune marker of claim 1.
Further, the immune-related molecule comprises at least one of CD3, CD4, CD8, CD56, CD45RA, CCR7, CD127, CD28, γ δ T, CXCR5, PD-1.
The invention also provides the application of the peripheral helper T cells as immune markers for normal pregnancy prediction.
In summary, the advantages and positive effects of the invention are:
the invention adopts multiple parametersFlow cytometry simultaneously detected 63 immune cell subtypes in peripheral blood of infertile women, born women and women with recurrent pregnancy loss (50 cases each group); through a plurality of groups of unpaired t tests, screening immune indexes with difference between a non-bearing woman group and a recurrent pregnancy loss group and between a bearing woman group and a recurrent pregnancy loss group as immune cell subtypes related to recurrent pregnancy loss, wherein the immune function indexes comprise: initial CD4+T cell, central memory CD4+T cell, effector memory CD4+T cell, terminally differentiated CD4+T cells, Treg cells, peripheral helper T cells, central CD8+T cell, terminally differentiated CD8+T-cell, non-active phase specific terminally differentiated CD8+T cell, depleted CD8+T cells, T NK cells, mature NK cells, immature NK/mature NK ratio, γ δ T cells.
The invention provides immune markers for detecting recurrent pregnancy loss of unknown reasons, and the immune markers comprise 15 cell subtypes. These subtypes of immune cells associated with recurrent pregnancy loss suggest that the immune system of a woman with recurrent pregnancy loss is under-tolerated and therefore unable to tolerate a fetus carrying a paternal antigen leading to the development of an abortion.
Drawings
FIG. 1 is a graph of data from an analysis of the detection of immune cell subtypes closely associated with recurrent pregnancy loss.
FIG. 2 is a ROC graph of 9 immune indexes with potential clinical application value;
FIG. 3 shows the results of ROC analysis of nine differential indicators in the born vs. non-born group and the recurrent pregnancy loss vs. non-born group.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples, and the equipment and reagents used in the examples and test examples are commercially available without specific reference. The specific embodiments described herein are merely illustrative of the invention and are not intended to be limiting.
Various modifications to the precise description of the invention will be readily apparent to those skilled in the art from the information contained herein without departing from the spirit and scope of the appended claims. It is to be understood that the scope of the invention is not limited to the procedures, properties, or components defined, as these embodiments, as well as others described, are intended to be merely illustrative of particular aspects of the invention. Indeed, various modifications of the embodiments of the invention which are obvious to those skilled in the art or related fields are intended to be covered by the scope of the appended claims.
For a better understanding of the invention, and not as a limitation on the scope thereof, all numbers expressing quantities, percentages, and other numerical values used in this application are to be understood as being modified in all instances by the term "about". Accordingly, unless expressly indicated otherwise, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. In the present invention, "about" means within 10%, preferably within 5% of a given value or range.
The normal temperature in the following embodiments of the present invention refers to a natural room temperature condition in four seasons, and is not subjected to additional cooling or heating treatment, and is generally controlled at 10 to 30 ℃, preferably 15 to 25 ℃.
The invention discloses a group of immune markers for diagnosis and treatment of recurrent pregnancy loss diseases and application thereof, and particularly relates to the following embodiments.
Example 1 screening of significantly different subtypes of immune cells in peripheral blood
The examples mainly include three groups of people: 50 non-pregnant women (non-pregnant group), 50 pregnant women (pregnant group) and 50 women with recurrent pregnancy loss (recurrent pregnancy loss group). The menstrual cycle of women in the non-bearing group and the bearing group is normal, and no adverse life history exists; women in the fertile group all delivered a normal child and had no history of poor fertility between 1 and 2 years after delivery. Women in the recurrent pregnancy loss group have had a history of spontaneous abortion or embryo abortion of two or more times before 20 weeks gestation, and have excluded chromosomal abnormalities, uterine anatomical abnormalities, prothrombotic states, endocrine factors, infections, and autoimmune diseases.
Each person in the examples 5ml of peripheral blood was drawn into heparin sodium treated blood collection tubes and tested within 24h after sampling.
After the peripheral blood was allowed to stand at room temperature, the upper plasma was aspirated, and the plasma was diluted with PBS buffer at a ratio of 1: 1, diluting, uniformly mixing, paving on the peripheral blood lymphocyte separation liquid, and performing density gradient centrifugation. The cells were collected and resuspended in RPMI1640 medium containing 10% fetal bovine serum, the flow antibody required for detection was added according to the instructions, incubated at 4 ℃ in the dark for 30min, washed twice with PBS, resuspended in separation buffer, and subjected to multiparameter flow cytometry detection using BD LSRFortessa X-20, and the results were analyzed using FlowJo V10 software.
63 of multiparameter flow cytometric analyses include: CD4 and CD8 of 41T cell subtypes, NK cell 10 subtypes and gamma delta T cell 12 subtypes.
The data distribution type is tested by Shapiro-Wilk, the normal distribution type is the mean and the standard deviation, and the skewed distribution data is represented by the median and the range; data differences were statistically analyzed using analysis of variance for multiple comparisons.
FIG. 1 shows 15 subtypes of immune cells closely related to recurrent pregnancy loss and successful pregnancy. Wherein, A-O: 15 subtypes of immune cells associated with recurrent pregnancy loss, including: initial CD4+T cell, central memory CD4+T cell, effector memory CD4+T cell, terminally differentiated CD4+T cells, Treg cells, peripheral helper T cells, central memory CD8+T cell, terminally differentiated CD8+T-cell, non-active phase specific terminally differentiated CD8+T cell, depleted CD8+T cells, T NK cells, mature NK cells, immature NK/mature NK ratio, γ δ T cells. A-D and L-M are immune indexes with statistical difference in comparison of a repeated pregnancy loss group vs. a born group and a repeated pregnancy loss group vs. a non-born group; f is simultaneously atThe immunity indexes of the recurrent pregnancy loss group vs. the non-bearing group and the born group vs. the non-bearing group are statistically different; e and H-K are immune indicators with statistical differences in repeated pregnancy loss group vs. born group comparison; g and N-O are immune indexes with statistical difference in comparison of repeated pregnancy loss group vs. non-bearing group; normal distribution data is represented by mean + -standard deviation, and skewed distribution data is represented by median + -extreme value. Data differences were statistically analyzed using analysis of variance for multiple comparisons. The difference level: p<0.05(*)；P<0.01(**)；P<0.001(***)；and P<0.0001(****). ns indicates that the difference is not statistically significant.
Example 2 clinical application value of the selected differential index
Three groups of people were included in the examples, 50 non-pregnant women (non-pregnant group), 50 pregnant women (pregnant group) and 50 women with recurrent pregnancy loss (recurrent pregnancy loss group). The menstrual cycle of women in the non-bearing group and the bearing group is normal, and no adverse life history exists; women in the fertile group all delivered a normal child and had no history of poor fertility between 1 and 2 years after delivery. Women in the recurrent pregnancy loss group have had a history of spontaneous abortion or embryo abortion of two or more times before 20 weeks gestation, and have excluded chromosomal abnormalities, uterine anatomical abnormalities, prothrombotic states, endocrine factors, infections, and autoimmune diseases.
The group of non-pregnant women, as represented by the group of non-pregnant women, was taken as the baseline pre-pregnant state for women of childbearing age. The 95% confidence intervals for the proportion of 15 immune cell subtypes in the peripheral blood of non-pregnant women, and the 95% confidence intervals for the same indices in normal pregnancy (born group) and recurrent pregnancy loss groups are shown in Table 1. The comparison shows that the confidence interval range of the 15 different immunity indexes is smaller in the group without fertility and the group with fertility, and is larger in the group with repeated pregnancy loss. Among them, the original CD4+T cells, central memory CD8+ T cells, mature NK cells and central memory CD4+The confidence interval of T cells was completely higher in the recurrent pregnancy loss group than in the non-fertile group, while effector memory CD4+T cells, immature NK cells, mature NK/immature NK ratio, peripheral helper T cellsAnd terminally differentiated CD4+The confidence interval for T cells was lower in the recurrent pregnancy loss group than in the non-fertile group; the 9 immune indexes are prompted to provide critical value judgment for prediction of repeated pregnancy loss diseases, and the critical value judgment has important reference value. The more the index detected by the peripheral blood immune function of the patient with recurrent pregnancy loss coincides with the index in the present embodiment, the higher the risk of recurrent pregnancy loss of the patient is suggested.
Table 1 summary of differential immune index function and its confidence intervals in each group
In addition, the 9 indexes of difference are subjected to receiver operating characteristic curve (ROC curve for short) (figure 2) and area under the curve (AUC) (figure 3) to analyze the critical value, sensitivity and specificity of disease prediction. Peripheral helper T cells were found to be of significant value in predicting normal pregnancy with a cutoff of 61.1% (specificity up to 88%, sensitivity 54%) in comparison between the fertile and non-fertile groups. In comparison between the recurrent pregnancy loss group and the non-bearing group, the p values of the 9 indexes are less than 0.01, which indicates that the method has important value for predicting recurrent pregnancy loss diseases, and the sensitivity and specificity of the method for diagnosing recurrent pregnancy loss are shown in figure 3 (recurrent pregnancy loss group vs. non-bearing group).
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (5)
1. A group of immune markers for diagnosing and treating recurrent pregnancy loss diseases, which is characterized in that the markers comprise primary CD4+T cell, central memory CD4+T cell, effector memory CD4+T cell, terminally differentiated CD4+T cells, Treg cells, peripheral helper T cells, central memory CD8+T cell, terminally differentiated CD8+T-cell, non-active phase specific terminally differentiated CD8+T cell, depleted CD8+At least one of T cells, T NK cells, mature NK cells, immature NK/mature NK ratio, γ δ T cells.
2. Use of a set of the biomarkers of recurrent pregnancy loss disease diagnosis and treatment according to claim 1 in the preparation of a reagent or a kit for diagnosing recurrent pregnancy loss disease.
3. A reagent or kit for diagnosing recurrent pregnancy loss disease, comprising a reagent for detecting an immune-related molecule expressed by the immune marker of claim 1.
4. The reagent or the kit for diagnosing and treating recurrent pregnancy loss diseases according to claim 3, wherein: the immune related molecules comprise CD3, CD4, CD8, CD56, CD45RA, CCR7, CD127, CD28, gamma delta T, CXCR5 and PD-1.
5. Use of peripheral helper T cells as an immune marker for the prediction of normal pregnancy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011338622.7A CN112557283A (en) | 2020-11-25 | 2020-11-25 | Diagnosis and treatment immune marker for recurrent pregnancy loss diseases and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011338622.7A CN112557283A (en) | 2020-11-25 | 2020-11-25 | Diagnosis and treatment immune marker for recurrent pregnancy loss diseases and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112557283A true CN112557283A (en) | 2021-03-26 |
Family
ID=75043596
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011338622.7A Pending CN112557283A (en) | 2020-11-25 | 2020-11-25 | Diagnosis and treatment immune marker for recurrent pregnancy loss diseases and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112557283A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113848169A (en) * | 2021-11-30 | 2021-12-28 | 广州普锐生物科技有限公司 | Healthy human immune cell activity evaluation and analysis method based on PD-1 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104360049A (en) * | 2014-09-22 | 2015-02-18 | 重庆医科大学附属儿童医院 | T lymphocyte immunophenotyping method and kit |
| CN110456057A (en) * | 2019-08-16 | 2019-11-15 | 江西普锐生物科技有限公司 | Detect the application and recurrent miscarriage detection kit and method of the reagent of immune function |
| CN111965370A (en) * | 2020-07-29 | 2020-11-20 | 深圳市锦欣医疗科技创新中心有限公司 | Biomarker for predicting pregnancy outcome of infertility patient and application thereof |
-
2020
- 2020-11-25 CN CN202011338622.7A patent/CN112557283A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104360049A (en) * | 2014-09-22 | 2015-02-18 | 重庆医科大学附属儿童医院 | T lymphocyte immunophenotyping method and kit |
| CN110456057A (en) * | 2019-08-16 | 2019-11-15 | 江西普锐生物科技有限公司 | Detect the application and recurrent miscarriage detection kit and method of the reagent of immune function |
| CN111965370A (en) * | 2020-07-29 | 2020-11-20 | 深圳市锦欣医疗科技创新中心有限公司 | Biomarker for predicting pregnancy outcome of infertility patient and application thereof |
Non-Patent Citations (8)
| Title |
|---|
| SAMANEH ABDOLMOHAMMADI VAHID 等: "Altered T‐cell subpopulations in recurrent pregnancy loss patients with cellular immune abnormalities", 《WILEY-CELLULAR PHYSIOLOGY》 * |
| БАТУРИНА И.Л.等: "АНАЛИЗ Т- И В-КЛЕТОК РАЗЛИЧНОГО УРОВНЯДИФФЕРЕНЦИРОВКИ И ИХ ПРОГНОСТИЧЕСКАЯ РОЛЬПРИ НЕВЫНАШИВАНИИ БЕРЕМЕННОСТИ", 《RUSSIAN JOURNAL OF IMMUNOLOGY /ROSSIYSKIY IMMUNOLOGICHESKIY ZHURNAL》 * |
| БОРЗОВА Н.Ю.1，等: "НОВЫЕ РАННИЕ ПРОГНОСТИЧЕСКИЕ КРИТЕРИИ ИСХОДА БЕРЕМЕННОСТИ У ПАЦИЕНТОК С ПРИВЫЧНЫМ ВЫКИДЫШЕМ", 《RUSSIAN CLINICAL LABORATORY DIAGNOSTICS》 * |
| ИВАНЕНКОВАН.И. 等: "ОСОБЕННОСТИ ДИФФЕРЕНЦИРОВКИТ_ЛИМФОЦИТОВ ПРИ УГРОЗЕ ПРЕРЫВАНИЯ БЕРЕМЕННОСТИ", 《ОРИГИНАЛЬНЫЕ СТАТЬИ》 * |
| 梁贤 等: "外周血单核细胞上Tim-3、PD-1在原因不明复发性流产及先兆流产中的表达特征及临床意义", 《中国计划生育学杂志》 * |
| 王莲莲 等: "复发性自然流产妇女外周血调节性T细胞和辅助性T细胞水平的表达", 《中国妇幼保健》 * |
| 肖敏 等: "早孕外周血及蜕膜中NK细胞表型及T淋巴细胞亚群的变化", 《细胞与分子免疫学杂志》 * |
| 蒋楠 等: "自然杀伤T细胞在不明原因习惯性流产患者外周血中的表达", 《CHINESE JOURNAL OF FAMILY PLANNING & GYNECOTOKOLOGY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113848169A (en) * | 2021-11-30 | 2021-12-28 | 广州普锐生物科技有限公司 | Healthy human immune cell activity evaluation and analysis method based on PD-1 |
| CN113848169B (en) * | 2021-11-30 | 2022-03-04 | 广州普锐生物科技有限公司 | Healthy human immune cell activity evaluation and analysis method based on PD-1 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bianchi et al. | Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data | |
| Gomez-Lopez et al. | The cellular transcriptome in the maternal circulation during normal pregnancy: a longitudinal study | |
| Murakami et al. | Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo | |
| US5830679A (en) | Diagnostic blood test to identify infants at risk for sepsis | |
| CN109072479A (en) | Spontaneous pre-term risk is layered using circulation particle | |
| Faron et al. | Prediction of preterm delivery by fetal fibronectin: a meta-analysis | |
| Fritz et al. | Trophoblast retrieval and isolation from the cervix (TRIC) is unaffected by early gestational age or maternal obesity | |
| Tekesin et al. | Evaluation and validation of a new risk score (CLEOPATRA score) to predict the probability of premature delivery for patients with threatened preterm labor | |
| CN115524490A (en) | HLA-DR + CD14 + CD56 + Use of monocytes for diagnosis in AA or HLH | |
| Yuan et al. | Combination of CD4+ CD25+ CD127-regulatory T cells with MLC-BE and BE-Ab2: an efficient evaluation of the therapy of paternal lymphocyte induced immunization in unexplained recurrent spontaneous abortion patients | |
| CN112557283A (en) | Diagnosis and treatment immune marker for recurrent pregnancy loss diseases and application thereof | |
| de Graaff et al. | Placental pathology findings amongst extremely preterm perinatal deaths in Aotearoa New Zealand | |
| CN110456057A (en) | Detect the application and recurrent miscarriage detection kit and method of the reagent of immune function | |
| Tripathi et al. | Maternal and perinatal outcome in Rh negative mothers | |
| Blackwell et al. | Unexplained fetal death is associated with changes in the adaptive limb of the maternal immune response consistent with prior antigenic exposure | |
| Eden et al. | The mammary stimulation test—A predictor of preterm delivery? | |
| Porstmann et al. | Immunochemical quantification of Cu/Zn superoxide dismutase in prenatal diagnosis of Down's syndrome | |
| CN112708653B (en) | Detection method for predicting recurrent abortion and/or diagnosing cause of recurrent abortion by menstrual blood | |
| RU2750787C1 (en) | Method for determining isoantigenic load in "mother-fetus-newborn" functional system | |
| Jari et al. | Association of undetectable unconjugated estriol on multiple marker screening with steroid sulfatase deficiency | |
| CN111506881B (en) | System for predicting Chinese Holstein cow mastitis onset risk | |
| Zafer et al. | Fetal cell detection for chromosome analysis from leaking amniotic fluid in pregnancies with rupture of membranes | |
| RU2623037C2 (en) | Method for prediction of primary hypothonic uterine dysfunction in primipara women | |
| Bond et al. | EVALUATION OF MEASUREMENT OF MATERNAL PLASMA ALPHA‐FETOPROTEIN LEVELS AS A SCREENING TEST FOR FETAL NEURAL TUBE DEFECTS | |
| Kazi | Mst Sadeka Tamanna, Dr. Fatema Akter Doly, Dr. Imran Mahmud, Dr. Khadiza Khan Toma, Dr. Farzana Mahmood. Associations between Severity of Thrombocytopenia & Pregnancy Induced HTN in a Tertiary Care Hospital: An Observational Study |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210326 |
|
| RJ01 | Rejection of invention patent application after publication |