Immunology Correlation Studies Between Vitamin D Or Its Receptor And Missed Abortion

Background and aimsVitamin D is a kind of necessary vitamins. Its active metabolite isl,25—(OH) 2D3. Vitamin D deficiency is common throughout the world, about 30—50%. Vitamin D3 less than 20ng/mL was defined as deficiency of vitamin D, vitamin D3 between 20—30 ng/mL is defined as a lack of vitamin D, vitamin D3 greater than 30ng/mL is defined as vitamin D normal. Over the years, the study of vitamin D calcium phosphate, only focused on the regulation of calcium and phosphorus and bone metabolism. In the past 20 years, but several studies have found that active vitamin D has immune regulating function. It is a new kind of neuroendocrine immune regulating hormones. It plays an important role on the regulation of cellular immunity, mainly displays in the monocyte/macrophage, T lymphocytes and B lymphocytes, and the influence of thymus cell proliferation differentiation and function of these cells.The biological effects of 1,25—(OH)2D3 is mediated by cells of the vitamin D receptor (VDR). Vitamin D receptor (VDR) is a steroid—thyroid hormone of members of the nuclear receptor superfamily, widely exists in the human body in a variety of tissue cells, in areas such as the uterus, ovary, placenta system also found the VDR, mainly mediated vitamin D biological effect of target cells. In addition to the classic regulating kidney, bowel loops—calcium phosphorus metabolism, in promoting embryonic muscle development and mature, regulating immune system, inhibiting tumor cell necrosis, infiltration and metastasis, it also plays a significant role in regulating cell proliferation and differentiation, etc.Missed abortion refers to the embryo or fetus has stranded intrauterine death failed to come out, it is a special type of abortion, it is a common diseases of obstetrics and gynecology. The incidence of missed abortion by about 13.4% has become an important public health problem. Modern reproductive immunology research shows that missed abortion also related to immune factors in addition to the common chromosomal abnormalities, environmental factors, endocrine abnormality, infection factors. Immune factors including autoimmune type and the same immune type. Same immune type that excludes the chromosomal abnormalities, abnormal anatomy, endocrine disorders, reproductive tract infections, autoimmune diseases, such as causes of abortion, clinically known as unexplained abortion. Process is as follows:from the perspective of the immunology pregnancy embryos with paternal antigen for matrix is a kind of graft, maternal immune system to recognize and generate a protective immune response, and fetal childbirth.Domestic studies have reported the occurrence of missed abortion and CD4+T cell mediated immunity enhancement, known CD4+T cells can be divided into two categories, Th 1 and Th2 subsets. Thl cells secrete IL—2, IFN—γ and TNF—β, etc. Giving priority to with IFN—γ, their function is mainly to promote cellular immunity, mainly involved in cellular immunity of autoimmune disease Th2 cells secrete IL—4、IL—5、IL-9、IL—10 and IL—13,giving priority to with IL—4, their main is to improve the humoral immune function,give priority to with antibody formation in humoral immune plays an important role. Study found that normal pregnancy maternal cells of immune function, humoral immune function, Thl/Th2 cells ratio offset in the direction of Th2 cells, advantage environment good for pregnancy, Th2 cells and Thl cytokines have embryo toxic effect, can hinder the development of early embryo, lead to pathological pregnancy. It generally believed that Thl cytokines can lead to miscarriage, Th2 type cytokines play an important role in maintaining normal pregnancy.Vitamin D3 can adjust antigen—presenting cells (APC), induce immune tolerance. affect the secretion of cytokines, increase IL—4 significantly,reduce IFN —γ significantly; Inhibition of the activity induced cell death, which have the effect of immunosuppression.The purpose of this experiment is to to discuss Vitamin D3 and its receptor and unexplained missed abortion immunology correlation by detecting the blood of the patients and normal pregnancy pregnant women vitamin D3 and decidual tissue in the vitamin D receptor, T lymphocyte subgroup and IFN —γ, IL—4. Finding a new means for the prevention and treatment of missed abortion.MethodsSelection of 2014.7 to 2015.7 in ShenZhen LuoHu district maternal and child health care hospital of meeting the following standards of missed abortion and pregnancy pregnant women, patients with missed abortion as abortion group,50 cases. Into a set of conditions:(1) at 10 to 12 weeks by ultrasound found embryonic development stops, centerless pulse; (2) the couple and (or) normal embryo chromosomes; (3) regular menstrual cycles; (4) sex hormones, thyroid function, blood sugar and insulin endocrine examination is normal; (5) out of genital tract infectious diseases, such as mold, mycoplasma, chlamydia infection; (6) cytomegalovirus, toxoplasma pathogens such as check the IgM are all negative; (7) check for antiphospholipid antibodies were negative for antiphospholipid syndrome.10—12 weeks to live births request to terminate pregnancies as normal control group,50 cases, the set of conditions:(1) no vaginal bleeding, abdominal pain and so on the pregnancy threatened abortion symptoms and signs; (2) Pulsed ultrasound confirmed normal embryonic development, cored pipe. Sample exclusion criteria:(1) has a history of spontaneous abortion, stillbirth; (2) have familial heredity history; (3) of department of gynaecology, ultrasound organic disease, and reproductive organs anatomic deformity genetic; (4) sex hormones, thyroid function, blood glucose, insulin endocrine aspects, such as abnormal or history of autoimmune diseases; (5) have genital tract infectious diseases, such as mold, mycoplasma and chlamydia infection; (6) cytomegalovirus, toxoplasma pathogens check IgM one is positive; (7) check for antiphospholipid antibodies positive for suspected or confirmed for antiphospholipid syndrome.By extracting two groups of men the extraction of peripheral venous blood tests of vitamin D3, IFN-γ, IL—4, whole blood for CD4+, CD8+flow cytometry detection. By surgery in two groups of men qing decidual tissue of immunohistochemical check the vitamin D receptor expression, data after finishing the SPSS 16.0 software was used to statistical analysis, inspection level on both sides to take P=0.05. Measurement data comparison between the two groups using the t test. The count of data between the two groups compared with χ2 test. Correlation analysis of various index using simple linear regression and correlation analysis.ResultsSelected cases of abortion group and the control group 50 cases each, statistical results are as follows:1、Abortion group of serum levels of CD4+/CD8+significantly higher than the control group,the difference was statistically significant (P=0.024<0.05); Abortion group serum IFN—γ is significantly higher than the control group, the difference was statistically significant (P=0.012<0.05); Abortion group of serum IL—4 was significantly lower than the control group, the difference was statistically significant (P=0.002<0.05); Abortion group of serum vitamin D3 was significantly lower than the control group, the difference was statistically significant (P=0.009<0.009)2、Vitamin D3 and positively correlated with IL—4,Vitamin D3 and CD4+/ CD8+,IFN—γ was negatively relation.3、100 samples by 1,25—(OH)2D3 concentrations quarterback grouping,the quarterback, the abortion rate of the quarterback was 72%, the abortion rate of the lower quartile was 32%, the quarterback group and the lower quartile by chi—square test,χ2=8.013 bilateral P= 0.01<0.05,the quarterback group and the quarterback abortion rates have statistical significance, two samples abortion rate have significant difference.4、With vitamin D3<20 ng/mL was defined as a lack of vitamin D,vitamin D3 in 20—30 ng/mL was defined as between vitamin D deficiency,with vitamin D3 is greater than 30 ng/mL is defined as a normal vitamin D, put all the vitamin D deficiency and insufficient samples, by chi—square test,the abortion rate in lack、 deficiency group and normal VitD3 level was statistically,χ2=6.741, P=0.028 on both sides<0.05.5、There is 76 cases of samples in decidual tissue with VDR expression,36 cases abortion group,40 cases control group, abortion group of serum levels of CD4 +/CD8+is higher than the control group,the difference was statistically significant(P=0.024<0.05); Abortion group serum IFN—γ is significantly higher than the control group, the difference was statistically significant (P=0.023 <0.05); Abortion group of serum IL—4 was significantly lower than the control group, the difference was statistically significant (P=0.020<0.05); Abortion group of serum vitamin D3 was significantly lower than the control group, the difference was statistically significant (P=0.048<0.05); Abortion group of decidual for the vitamin D receptor level lower than the control group, there was no statistically significant difference (P=0.558>0.05)6、There is 24 cases of samples in decidual tissue without VDR expression,14 cases abortion group,10 cases control group abortion group of serum levels of CD4 +/CD8+is higher than the control group,there was no statistically significant difference (P=0.734>0.05); Abortion group serum IFN—γ is higher than the control group, there was no statistically significant difference (P=0.537>0.05); Abortion group of serum vitamin D3 was significantly lower than the control group, there was no statistically significant difference (P=0.06>0.05); Abortion group of serum IL—4 was significantly lower than the control group, the difference was statistically significant (P=0.024< 0.05)Conclusion1、Missed abortion occurrence and CD4+T cell mediated immunity enhancement,there is lack of vitamin D3. Vitamin D3 levels in the serum is correlated with missed abortion. Vitamin D deficiency cause missed abortion is by changing the proportion of CD4+/CD8+, affect cellular immune balance, break the Th1/Th2 balance.2、Pregnant women generally lack vitamin D3 and deficiencies. In lack vitamin D3 group, deficiency group and normal group, the abortion rate is significant differences.3、When the decidual tissues can express the vitamin D receptor, the concentration of vitamin D3 has correlation with missed abortion, but the number of decidual tissue vitaminD receptor expression is not associated with missed abortion.