IL-33 and Soluble ST2 Are Associated With Recurrent Spontaneous Abortion in Early Pregnancy

Abstract

Normal pregnancy is related to the successful transition from type 1 cellular immunity to type 2 cellular immunity. Therefore, this study aimed to investigate whether there is abnormal expression of cytokines in the process of inducing Recurrent spontaneous abortion (RSA). Interleukin (IL)-33 is a new member of the IL-1 family, and ST2, as IL-33's receptor, induced the production of type 2 cytokines. In this study, blood samples were collected from 19 non-pregnant women of normal childbearing age, 28 normal pregnant women, and 33 women with RSA. The serum concentrations of IL-33 and ST2 were detected by flow cytometry. Our results showed that the serum concentrations of IL-33 and ST2 in the RSA group were significantly higher than those in the healthy control group (IL-33: P < 0.05; ST2: P < 0.0001), and IL-33 and ST2 had a higher level in the process of RSA predictive value. In addition, this study initially found that the serum concentrations of IL-33 and ST2 were not significantly correlated with the number of weeks of pregnancy, and there was a lower correlation between IL-33 and ST2 during RSA. This result may be related to the small number of cases. This study is the first time to correlate the changes in serum concentrations of IL-33 and ST2 with RSA, which may be a novel biomarker for the prediction and treatment of RSA.

Keywords: IL-33; ST2; biomarker; diagnosis; recurrent spontaneous abortion.

FIGURE 1

Serum IL-33 and ST2 levels at 7–19 weeks of gestation. (A) Analysis of serum IL- 33 in the normal non-pregnancy, normal pregnancy, RSA non-pregnancy and RSA pregnancy groups. (B) Analysis of soluble ST2 in the same groups. (^∗p < 0.05 versus normal pregnancy group; ^∗∗∗∗p < 0.0001 versus normal pregnancy group).

FIGURE 2

Predictive value of maternal serum IL-33 and ST2 level in RSA. (A) ROC curve analysis of serum IL-33 level in the pregnancy groups, AUC=0.6660. (B) ROC curve analysis of serum solubleST2 level in the pregnancy groups, AUC=0.9087. (C) ROC curve analysis of serum IL-33 and sST2 levels in the pregnancy groups, AUC = 0.9107. (D) ROC curve analysis of serum IL-33 level in the non-pregnancy groups, AUC=0.8684. (E) ROC curve analysis of serum solubleST2 level in the non- pregnancy groups, AUC=0.8465. (F) ROC curve analysis of serum IL-33 and sST2 levels in the non-pregnancy groups, AUC=0.8509.

FIGURE 3

Relationship between maternal serum IL-33 and sST2 level and gestational age. (A) Correlation between serum IL-33 and weeks of gestation in normal pregnancy group. (B) Correlation of soluble ST2 with the number of weeks of gestation in normal pregnancy group. (Values corresponding to the same number of weeks of gestation are plotted using their mean values). Relationship between maternal serum IL-33 and ST2 level and gestational weeks. (C) Correlation between serum IL-33 and weeks of gestation in RSA pregnancy group. (D) Correlation of soluble ST2 with the weeks of gestation in RSA pregnancy group. (Values corresponding to the same number of weeks of gestation are plotted using their mean values). Relationship between maternal serum IL-33 and ST2 level and age. (E) Correlation between serum IL-33 and age in normal group. (F) Correlation between serum soluble ST2 and age in normal group. Relationship between maternal serum IL-33 and ST2 level and age. (G) Correlation between serum IL-33 and age in diseased group. (H) Correlation between serum soluble ST2 and age in diseased group.

FIGURE 4

Relationship between maternal serum IL-33 and ST2 level and number of miscarriage. (A) Correlation between serum IL-33 and number of miscarriage. (B) Correlation between serum soluble ST2 and number of miscarriage.

FIGURE 5

Correlation of maternal serum IL-33 and ST2 level. (A) Correlation analysis between serum IL-33 and ST2 level in the normal pregnancy group. (B) Correlation between serum IL-33 and ST2 level in the RSA pregnancy group. (Values corresponding to the same number of weeks of gestation are plotted using their mean values).