CN114774504A - Marker related to female immune state, reproductive potential and reproductive aging state and application - Google Patents

Marker related to female immune state, reproductive potential and reproductive aging state and application Download PDF

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CN114774504A
CN114774504A CN202210452097.4A CN202210452097A CN114774504A CN 114774504 A CN114774504 A CN 114774504A CN 202210452097 A CN202210452097 A CN 202210452097A CN 114774504 A CN114774504 A CN 114774504A
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treg
cells
reproductive
hla
immune
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廖爱华
木洋
宋苏
蔺新秀
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Huazhong University of Science and Technology
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    • G01N2333/70514—CD4
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    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
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    • G01N2333/70589—CD45
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    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
    • G01N2333/7155—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
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    • G01N2500/00—Screening for compounds of potential therapeutic value
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    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Abstract

The application discloses a marker related to female immune state, reproductive potential and reproductive aging state and application thereof, wherein the marker comprises HLA-DR+CD45 RA-Treg cells and/or CD 28-Treg-like cells. With age, CD 28-Treg-like cells and HLA-DR+The proportion of the CD45 RA-Treg cell subset is obviously increased by the treatment of HLA-DR+Whether the CD45 RA-Treg cells and CD 28-Treg-like cells exceed the upper limit of the reference value range or not evaluates the low prognosis and low reproductive potential of patients on ART treatment.

Description

Marker related to female immune state, reproductive potential and reproductive aging state and application
Technical Field
The application relates to the technical field of female reproductive state related markers, in particular to a marker related to female immune state, reproductive potential and reproductive aging state and application thereof.
Background
Reproductive senescence is a physiological process that occurs in all women and is associated with a decrease in the number and quality of ova produced by the ovaries and a low fertility potential. Diminished ability of the ovary to produce ova and decreased follicular quality are also considered to be manifestations of diminished ovarian reserve. Female reproductive system aging precedes other organ systems and is associated with immune aging and chronic inflammation. The current evaluation of reproductive potential and fertility in women of child bearing age mainly comprises physical examination, ultrasonic examination and biochemical detection of reproductive hormone levels, but the examinations cannot reflect the immune state of the mother body and lack specific immune markers. Although female reproductive potential can be assessed through these examinations, predicting the potential for fertility decline through current examination approaches remains challenging.
Disclosure of Invention
The inventor discovers HLA-DR by detecting the proportion of Treg cell subsets in the blood serum of women of different age groups and analyzing the correlation between each Treg cell subset and age and ovary reserve markers of women of childbearing age+The proportion of the CD45 RA-Treg cell subgroup and the CD 28-Treg cell has obvious correlation with the age of women of reproductive age and ovarian reserve markers, and the suggestion is that HLA-DR+The CD45 RA-Treg cell subgroup and CD 28-Treg-like cell ratio have great potential as markers for the determination of the immunological, reproductive and/or reproductive senescence status of women, and are based on HLA-DR+The method for clinically diagnosing the risks of the patients with reproductive senescence and low reproductive potential is established on the basis of the proportion of the CD45 RA-Treg cell subgroup and the CD 28-Treg-like cells.
In a first aspect, the present application discloses a marker associated with at least one of the immune status, reproductive potential and reproductive senescence status of a female, including HLA-DR+CD45 RA-Treg cells and/or CD 28-Treg-like cells.
In a second aspect, the present application discloses the use of a combination of markers as defined in the first aspect for the preparation of a reagent or kit for predicting and/or assessing the immune status, reproductive potential and/or reproductive senescence status of a female.
In a third aspect, the present application discloses the use of the marker combination defined in the first aspect for screening for the preparation of a medicament for treating or preventing hypoimmunity, reduced reproductive potential and/or reproductive aging in women.
In a fourth aspect, the present embodiments disclose a reagent or kit for predicting and/or assessing the immune status, reproductive potential and/or reproductive senescence status of a female comprising reagents for detecting an immune-related molecule expressed by a marker combination as defined in claim 1.
In embodiments of the application, wherein the immune-related molecule comprises at least one of CD3, CD4, CD25, CD45RA, CD127, CD28, and HLA-DR.
In the embodiments herein, wherein the immune-related molecule comprises a combination of CD3, CD4, CD25, CD45RA, CD127, CD28, and HLA-DR.
In a fifth aspect, the examples of the present application disclose the use of the marker defined in the first aspect in the preparation of a reagent or kit for prognosis prediction and/or assessment of assisted reproductive technologies treatment in women.
In an embodiment of the present application, said predicting and/or said evaluating comprises:
establishment of HLA-DR+Reference value ranges for CD45 RA-Treg cells and CD 28-Treg-like cells;
extracting mononuclear cells from a peripheral blood sample of a subject, and detecting HLA-DR therefrom+CD45 RA-Treg cell and CD 28-Treg-like cell ratio;
judging HLA-DR of subject+Whether the proportion of CD45 RA-Treg cells and CD 28-Treg-like cells exceeds the upper limit of the range of the reference value;
if so, the subject is indicated to have a low prognostic value and low reproductive potential for treatment with assisted reproductive technologies.
In the examples of the application, the reference value ranges are based on HLA-DR of peripheral blood of Chinese female population aged 20-24 years and 25-29 years+Data for the proportion of CD45 RA-Treg cells and the proportion of CD 28-Treg-like cells were established.
Compared with the prior art, the application has at least one of the following beneficial effects:
it was found in this application that, with increasing age, CD 28-Treg-like cells and HLA-DR+The proportion of CD45 RA-Treg cell subset is obviously increased. In addition, the Treg subpopulation was found to have a clear correlation with age and the ovarian reserve markers currently used to assess female reproductive potential. The application hereby establishes a reference value range by comparing HLA-DR+CD45 RA-Treg cells and CD28-Treg-like cell proportion exceeds the upper limit of the range of reference values to assess whether patients treated with ART have low prognostic value and low reproductive potential. These results indicate HLA-DR+CD45 RA-Treg cells and CD 28-Treg-like cells have the potential to serve as immunological markers reflecting reproductive senescence, can help clinicians identify patients of low reproductive potential, and establish individualized treatment strategies.
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FIG. 1 shows the results of multiparameter flow cytometry analysis of peripheral immune cell subsets as provided in the examples herein; (A) lymphocytes; (B) CD3+A T cell; (C) CD4+A T cell; (D) total Treg cells (CD 4)+CD25+CD 127-); (E) CD 28-Treg-like cell (CD 28-CD 3)+CD4+CD25+CD127 —) and CD28+Treg-like cells (CD 28)+CD3+CD4+CD25+CD 127-); (F) CD45 RA-Treg cell (CD 3)+CD4+CD25+CD 127-CD 45 RA-and CD45 RA-)+Treg cells (CD 3)+CD4+CD25+CD127ˉCD45RA+) (ii) a (G) HLA-DR-CD 45 RA-Treg cell (CD 3)+CD4+CD25+CD 127-CD 45 RA-HLA-DR-and HLA-DR+CD45 RA-Treg cell (CD 3)+CD4+CD25+CD127ˉCD45RAˉHLA-DR+)。
FIG. 2 is a graph showing markers reflecting ovarian reserve function among age groups, including Follicle-stimulating hormone (FSH) (A), provided by an example of the present application; luteinizing Hormone (LH) (B); antimir-mullerian hormone (AMH) (C) and ultrasound examination of Antral Follicle Count (AFC) (D); FIGS. 2E and 2F are comparative statistical plots of FSH levels, AMH levels and AFC, respectively, between age groups; data are expressed as mean ± standard deviation; p <0.05, P <0.01, P <0.001, P < 0.0001.
Fig. 3 is a graph of the ratio of total Treg cells and different subpopulations of Treg cells of different age groups as provided by the examples of the present application; (A) total Treg cells (CD 3)+CD4+CD25+CD127ˉ)；(B)CD28+Treg-like cells (CD 28)+CD3+CD4+CD25+CD 127-); (C) CD 28-Treg-like cell (CD 28-CD 3)+CD4+CD25+CD 127-); (D) naive Treg cells (CD 3)+CD4+CD25+CD127ˉCD45RA+) (ii) a (E) Memory Tregs (CD 3)+CD4+CD25+CD127ˉCD45RAˉ)；(F)HLA-DRˉCD45RAˉTregs(CD3+CD4+CD25+CD127ˉCD45RAˉHLA-DRˉ)；(G)HLA-DR+CD45RAˉTregs(CD3+CD4+CD25+CD127ˉCD45RAˉHLA-DR+) (ii) a (H) CD 28-Treg-like cells and HLA-DR+CD45 RA-Treg cells; comparative statistical plots between different age groups; data are expressed as mean ± standard deviation. P<0.05,**P<0.01,****P<0.0001。
FIG. 4 shows age, ovarian reserve markers (FSH, AMH and AFC) and significantly altered Treg subpopulations (HLA-DR) provided in the examples of the present application+CD45 RA-Treg cells and CD 28-Treg-like cells); (A) is the correlation of age with reproductive hormones (FSH and AMH levels); (B) age and AFC correlation; (C) is an age and significantly altered Treg subgroup (CD 28-Treg-like cells and HLA-DR)+CD45 RA-Treg cells); (D) is HLA-DR+Correlation of CD45 RA-Treg cells with FSH; (E) is HLA-DR+Correlation of CD45 RA-Treg cells and AMH levels; (F) is HLA-DR+Correlation of CD45 RA-Treg cells with AFC; (G) is the correlation between CD 28-Treg-like cells and AFC.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application. Reagents not individually specified in detail in this application are conventional and commercially available; methods not specifically described in detail are all routine experimental methods and are known from the prior art. The specific implementation process is as follows:
1. study object
This example divides 88 women of childbearing age (subjects) into four groups (22 each) according to age: 20-29 years old, 30-34 years old, 35-39 years old, and 40-49 years old. The subject has regular menstrual cycle, normal number of ovaries, no history of ovarian surgery, no endometriosis and no endocrine disturbance. Women using hormonal contraceptives and women with autoimmune disease, genetic disease, congenital disease, undergoing pelvic surgery, radiation therapy or autoimmune endocrine disease were excluded. Table 1 statistics of the main characteristics of the study population including the proportion of persons at each age stage, mean age, body mass index, follicle stimulating hormone, luteinizing hormone, estradiol, anti-mullerian hormone and antral follicle count for 88 subjects.
TABLE 1 clinical data
Figure BDA0003619047790000051
2. Research method
(1) Collecting blood sample
Peripheral Blood (5 mL) was collected from the antecubital vein of a subject during the menstrual cycle, and after standing at room temperature for coagulation, the obtained serum was centrifuged, and the obtained serum was separated under aseptic conditions, Peripheral Blood Mononuclear Cells (PBMCs) were separated by density centrifugation, and the cells were washed with RPMI 1640 containing 10% fetal bovine serum (Gibco) and tested.
(2) Detection of reproductive hormones
In UniCelTMDxI800 Beckman 10
Figure BDA0003619047790000062
In the immunoassay system, the AMH level is detected by particle chemiluminescence analysis (CIMA). LH and FSH levels are measured using electrochemiluminescence immunoassay (ECLIA), Roche
Figure BDA0003619047790000063
A 8000 module analyzer and an immunoassay module (e602, roche diagnostics international limited, rott kruz, switzerland). The results of measuring the serum AMH, FSH, LH levels are shown in Table 1Shown in the figure.
(3) Antral follicle count assay
On days 2 to 4 of the natural menstrual cycle, subjects examined AFC using transvaginal ultrasound scans at a frequency of 9MHz (HD11XE, Bothell, WA). The antral follicle is a small follicle with a diameter of about 2-9 mm in the ovary of a woman. If 1-2 or more antral follicles are not observed, AFC is defined as invisible.
(4) Detection of Treg cell subpopulations in peripheral blood by multiparameter flow cytometry
PBMCs were washed twice with staining buffer (PBS containing 10% fetal bovine serum) and the corresponding fluorochrome-labeled monoclonal antibody (Table 2) was added and incubated for 30 minutes at 4 ℃ according to the instructions. PBS was washed twice, the cells were resuspended in isolation buffer, and multi-parameter flow cytometric assay was performed using BD LSRFortessa X-20, and the results were analyzed using FlowJo V10 software (Tree Star) software.
TABLE 2 monoclonal antibody information for multiparameter flow cytometry
Figure BDA0003619047790000061
Wherein each cell subpopulation of the multiparameter flow cytometer analysis comprises: total Treg cells (CD 3)+CD4+CD25+CD127ˉ)、CD28+Treg-like cells (CD 28)+CD3+CD4+CD25+CD 127-, CD 28-Treg-like cells (CD 28-CD 3-)+CD4+CD25+CD 127-, naive Treg cells (CD 3)+CD4+CD25+CD127ˉCD45RA+) Memory Tregs (CD 3)+CD4+CD25+CD 127-CD 45 RA-, HLA-DR-CD 45 RA-Treg cells (CD 3-)+CD4+CD25+CD127ˉCD45RAˉHLA-DRˉ)、HLA-DR+CD45 RA-Treg cell (CD 3)+CD4+CD25+CD127ˉCD45RAˉHLA-DR+)。
(5) Statistical analysis
Statistical analysis was performed using SPSS statistical software version 20.0 and GraphPadPrism version 8.0. All data were evaluated for distribution normality using the Shapiro-Wilk test. Quantitative data are expressed as mean ± standard deviation and classification values are expressed as number (n) and percentage (%). For skewly distributed data, the data is represented as median and extrema (minimum and maximum).
In this application, the "median" of a sequentially ordered set of data represents a value in a sample, population, or probability distribution that divides the set of values into equal upper and lower portions. For a finite number set, the median can be found by sorting all the observed values from large to small. If there are an even number of observations, the median is usually taken as the average of the two most intermediate values.
In the present application, "reference value range" is referred to as "median", for example, all observed values are sorted from small to large, and 5 percentile and 95 percentile are respectively calculated, wherein the 5 th percentile is used as the lower limit of the reference value range, and the 95 th percentile is used as the upper limit of the reference value range. Correspondingly, the median is the 50% percentile.
For example, HLA-DR is calculated separately+The CD45 RA-Treg cells and CD 28-Treg-like cells are distributed in proportion in the peripheral blood of a female population between 20 and 29 years old, and the 5 th percentile is used as the lower limit of the reference value range, and the 95 th percentile is used as the upper limit of the reference value range.
Wherein, the calculation methods of the "5 th percentile" and the "95 th percentile" refer to the following: arranging the raw data in increasing order (i.e., from small to large); calculating an index i which is n × p% (n is the number of original data, p is a percentile value, such as 5 of the 5 th percentile and 95 of the 95 th percentile); if i is not an integer, taking the i upward as an integer, wherein the adjacent integer larger than i is the position of the p percentile; if i is an integer, the p percentile is the average of the i th and (i +1) th items of data.
Comparison of categorical variables was performed using the pearson chi-square test. Differences between groups were assessed by T-test. One-way anova (multiple comparisons) was used to determine the apparent difference between the three groups. The pearson correlation coefficient was used to assess the relationship between age, ovarian reserve markers (FSH, AMH and AFC) and Treg subpopulations.
3. As a result, the
(1) Ovarian reserve biomarkers for different age groups
The results are shown in fig. 2, where FSH levels, AMH levels and AFC counts all increased significantly with age; LH levels were not different between age groups. It can be seen that there is a clear positive correlation between FSH levels and age, whereas AFC levels and AMH levels are negatively correlated with age, respectively. Currently, FSH, AFC and AMH are used as biomarkers associated with ovarian reserve function in the prior art.
(2) The change of each Treg cell subgroup with age
The experiment uses multi-parameter flow cytometry to detect the change condition of Treg cell subsets in peripheral blood of different age groups along with the age increase. Figure 3 compares the percentage of total Treg cells and each Treg cell subpopulation for different age groups.
As shown in fig. 3A, total Treg cells did not change significantly with age in the subject. As shown in FIG. 3B, CD28+Treg-like cells decrease with age. As shown in FIG. 3C, CD 28-Treg-like cells increased significantly with age. As shown in fig. 3D, CD45RA+Treg cells decrease significantly with age. As shown in FIG. 3E, CD45 RA-Treg cells increased significantly with age. Further analysis revealed HLA-DR, as shown in FIGS. 3F and 3G+The CD45 RA-Treg cell subset is obviously increased along with the increase of age, while the HLA-DR+CD45 RA-Treg cells were not significantly different between age groups.
From this, the results are combined, as shown in FIG. 3H, HLA-DR+CD45 RA-Treg cell and CD28+Treg-like cells all increase obviously with age and are in positive correlation.
(3) Ovarian reserve markers and HLA-DR+CD45 RA-Treg cell and CD28+Relevance of Treg-like cells
Due to HLA-DR+CD45 RA-Treg cell and CD28+Treg-like cell homoeographyThe correlation with age is present and similar to the correlation of ovarian reserve markers with age. This example further discusses ovarian reserve markers and HLA-DR+CD45 RA-Treg cell and CD28+Association of Treg-like cells. Figure 4 shows the correlation between age and ovarian markers such as AMH, FSH and AFC, as well as the correlation between Treg subpopulations that change significantly with age.
Figure 4A shows that FSH levels are significantly positively correlated with age, while AMH levels are significantly negatively correlated. Figure 4B shows a clear negative correlation of AFC levels with age. FIG. 4C shows HLA-DR+Both CD45 RA-Treg cells and CD 28-Treg-like cells are obviously and positively correlated with the age of the subject. FIG. 4D shows HLA-DR+CD45 RA-Treg cells were clearly positively correlated with FSH levels. FIGS. 4E and 4F show HLA-DR+The proportion of CD45 RA-Treg cells was clearly inversely correlated with both AMH and AFC levels. FIG. 4G shows that there is a significant positive correlation between the proportion of CD 28-Treg-like cells and AFC counts.
(4) HLA-DR for different age groups based on reference value range+Distribution of CD45 RA-Treg cells and CD 28-Treg-like cells
HLA-DR in view of the clear correlation with age and ovarian reserve markers within the reference range+The proportion of CD45 RA-Treg cells and CD 28-Treg-like cells can be used as an immune marker of reproductive senescence. Thus, this step establishes the HLA-DR basis+Methods for predicting and/or assessing clinically identifiable patients of low reproductive potential using reference value ranges for both cell subsets of CD45 RA-Treg cells and CD 28-Treg-like cells.
In embodiments of the present application, the method of predicting and/or evaluating clinically identified patients of low reproductive potential specifically comprises:
establishment of HLA-DR+Reference value ranges for CD45 RA-Treg cells and CD 28-Treg-like cells;
extracting peripheral blood mononuclear cells from a subject, and detecting HLA-DR therein+CD45 RA-Treg cell and CD 28-Treg-like cell ratio;
judging HLA-DR of subject+Whether the proportion of CD45 RA-Treg cells to CD 28-Treg-like cells is overGenerating the upper limit of the reference value range;
if so, the subject is indicated to have a low prognostic value and low reproductive potential for treatment with assisted reproductive technologies.
In a specific embodiment, the reference value range is based on HLA-DR of peripheral blood of Chinese female population aged 20-24 years and 25-29 years+Data for the CD45 RA-Treg cell proportion and the CD 28-Treg-like cell proportion were established.
For example, in the present example, HLA-DR was calculated separately+The median and 5 th and 95 th percentiles of the ratios of CD45 RA-Treg cells and CD 28-Treg-like cells in peripheral blood are shown in Table 3, HLA-DR+The reference value ranges of the CD45 RA-Treg cells and the CD 28-Treg-like cells are 3.46 to 13.69 percent and 0.08 to 0.97 percent respectively.
TABLE 3 HLA-DR+Reference value ranges for CD45 RA-Treg and CD 28-Treg cells
Figure BDA0003619047790000101
As shown in Table 4, HLA-DR was evaluated using established reference value ranges+Distribution of CD45 RA-Treg cells and CD 28-Treg-like cells in the general population studied and in subgroups of different ages, HLA-DR in most subjects+The proportions of CD45 RA-Treg cells and CD 28-Treg-like cells were within the corresponding reference values, and the coverage was 87.4% and 72.4%, respectively; but exceeds CD 28-Treg-like cells and HLA-DR with age+The proportion of subjects in the upper limit of the reference range of CD45 RA-Treg cells increases.
TABLE 4 HLA-DR+Reference value range distribution of CD45 RA-Treg and CD 28-Treg cells
Figure BDA0003619047790000111
(5)HLA-DR+Women with a ratio of CD45 RA-Treg cells to CD 28-Treg-like cells exceeding the reference value range are in Assisted Reproductive Technology (ART)Has low reproductive potential and low prognostic value.
HLA-DR established according to the above+The reference value ranges corresponding to the CD45 RA-Treg cells, the CD 28-Treg cells, the biochemical and ultrasonic ovarian reserve markers are divided into groups for the study population: HLA-DR+The percentage of CD45 RA-or CD 28-Treg-like cells which is higher than the upper limit of the reference value range is designated as group 1 and is located within the reference value range is designated as group 2. The mean age and ovarian reserve marker levels were then compared between the two groups.
TABLE 5 comparison of Treg subpopulations within reference value range and upper range limits with respective reserve markers
Figure BDA0003619047790000112
The results are shown in Table 5, HLA-DR+The median age and median FSH level of the CD45 RA-Treg cells above the upper limit of the range of reference values correspond to a significantly higher median age and median FSH level, respectively, lying within the range of reference values; while the median AMH and AFC levels that exceed the upper limit of the range of reference values are significantly lower than the median level within the range of reference values.
As in Table 5, the median age of CD 28-Treg-like cells above the upper limit of the range of reference values is significantly higher than the median age within the range of reference values; while the median AFC level above the upper limit of the range of reference values is significantly lower than the median AFC level that lies within the range of reference values.
It follows that the use of a range of reference values can be used to predict the prognosis of an elderly female with ART treatment, HLA-DR+Women with a proportion of CD45 RA-Treg-and CD 28-Treg-like cells which exceeds the upper limit of the range of reference values are classified as low prognosis and are not recommended for ART therapy, respectively.
For identification, the present embodiments establish HLA-DR+The reference value ranges of the CD45 RA-Treg cells and the CD 28-Treg-like cells are used as a benchmark to help clinicians identify women with low reproductive potential and help to improve the diagnosis efficiency.
In summary, it is found in the present application that with age, C increasesD28-Treg-like cells and HLA-DR+The proportion of the CD45 RA-Treg cell subpopulation was significantly increased, and both subpopulations were found to be significantly correlated with age and the ovarian reserve marker currently used to assess reproductive potential. The present application establishes reference value ranges accordingly by matching HLA-DR+Whether the CD45 RA-Treg cells and CD 28-Treg-like cells exceed the upper limit of the reference value range or not evaluates the low prognosis and low reproductive potential of patients on ART treatment. These results indicate that these HLA-DRs+CD45 RA-Treg and CD 28-Treg-like cells may be useful immune markers reflecting reproductive senescence, and may help clinicians identify patients of low reproductive potential and establish individualized treatment strategies.
The above description is only for the preferred embodiment of the present application, but the scope of the present application is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present application should be covered within the scope of the present application.

Claims (9)

1. A marker associated with at least one of immune status, reproductive potential and reproductive senescence status in a female, comprising HLA-DR+CD45 RA-Treg cells and/or CD 28-Treg cells.
2. Use of a combination of markers as defined in claim 1 for the preparation of a reagent or kit for predicting and/or assessing at least one of the immune status, reproductive potential and reproductive senescence status of a female.
3. Use of a combination of markers as defined in claim 1 for the screening for the manufacture of a medicament for the treatment or prevention of immune hypofunction, decreased fertility, decreased reproductive potential and/or reproductive aging in a female.
4. A reagent or kit for predicting and/or assessing at least one of the immune status, reproductive potential and reproductive senescence status of a female comprising a reagent for detecting an immune-related molecule expressed by the marker combination defined in claim 1.
5. The agent or kit of claim 4, wherein the immune-related molecule comprises at least one of CD3, CD4, CD25, CD45RA, CD127, CD28, and HLA-DR.
6. The agent or kit of claim 5, wherein the immune-related molecule comprises a combination of CD3, CD4, CD25, CD45RA, CD127, CD28, and HLA-DR.
7. Use of the marker of claim 1 in the preparation of a reagent or kit for prognosis prediction and/or assessment of assisted reproductive technology treatment in women.
8. The use of claim 6, wherein the predicting and/or the evaluating comprises:
establishment of HLA-DR+Reference value ranges for CD45 RA-Treg cells and CD 28-Treg-like cells;
extracting peripheral blood mononuclear cells from a subject, and detecting HLA-DR therein+CD45 RA-Treg cells and CD 28-Treg-like cells;
judging HLA-DR of a subject+Whether the proportion of CD45 RA-Treg cells to CD 28-Treg-like cells exceeds the upper limit of the range of the reference value;
if so, the subject is indicated to have a low prognostic value and low reproductive potential for treatment with assisted reproductive technologies.
9. The use according to claim 7, wherein the reference value range is based on peripheral blood HLA-DR for a 20-24 year old and 25-29 year old Chinese female population+Data for the proportion of CD45 RA-Treg cells and the proportion of CD 28-Treg-like cells were established.
CN202210452097.4A 2022-04-27 2022-04-27 Marker related to female immune state, reproductive potential and reproductive aging state and application Pending CN114774504A (en)

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