N and mucin domain (Tim) protein family, which was first identified
N and mucin domain (Tim) protein family, which was first identified in 2001 [7], is selectively expressed on Th1 cells but not on Th2 cells and can induce the apoptosis of Th1 cells after specific binding with its main ligand galectin-9 [8]. Popovici et al. found that the expression of galectin-9 was much higher in early decidual cells than in nonpregnant endometrium epithelial cells [9]. Thus,it is likely that allograft tolerance weakens after the Tim/galectin-9 pathway is blocked, for the dismissal of Th1 cell suppression and the enhanced function of Th1 cells, including the upregulated expression of Th1 cytokines and Th1-type immune response overbalance. Inversely, activating the Tim-3/galectin-9 pathway would suppress the immune response of Th1 cells and benefit the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 immune tolerance of allografts [5]. Moreover, Tim-3 expressed on natural killer (NK) cells was found to be elevated when they were activated, suppressing the NK-dependent immune response and strengthening immune tolerance [10]. Tim-3 polymorphism has also been shown to change the interaction between Tim-3 and its ligand, thereby affecting the processes leading to some immune diseases [11]. Given all these findings, Tim-3 might be an important regulatory molecule that plays a pivotal role in URSA, which might be triggered mostly by Th1/Th2 immune deviation. Whether anomalies in the activation of the Tim-3/gelatin-9 pathway, for example, change in thestructure of Tim-3/gelatin-9, their abnormal expression, or mutual interaction lead to URSA, remains unknown. Tim-3/Tim-3 polymorphisms and their association with URSA in Han Chinese women have not been studied thus far. Here, we examined polymorphisms of rs10053538/ rs10515746 loci in the promoter of Tim-3 and their relevance to URSA in Han Chinese women.Methods The protocols of this research were approved by the Ethics Committee of Taizhou Hospital. Written informed consent was obtained from all patients engaged in this study at the start of the research. Because all the researchers of this study work for Taizhou Hospital, which is located in Taizhou, Zhejiang, a Han Chinese habitation in China, all subjects selected were Han Chinese women.Patients and DNA 4,4,5,5-Tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolane samplesOne hundred and forty-eight women with RSA resulting in still birth were enrolled from the Obstetrics and Gynecology Department 2-Chloro-5,6-dihydro-7H-cyclopenta[b]pyridin-7-one of Taizhou Hospital to comprise the research group. In addition, 153 patients with normal pregnancy culminating in live birth were selected at random from the Obstetrics and Gynecology Department of Taizhou Hospital to form the control group. They had delivered at least 1 full-term healthy baby without the aid of assisted reproductive technologies and had not experienced miscarriage or pregnancy complications in the past. The abortions included both embryonic and anembryonic losses before 20 weeks of gestational age, which were determined by ultrasound dating and/or dating based on the last menstrual period. All PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/10811056 subjects had undergone a comprehensive examination, including determination of detailed medical history, physical examination, beta subunit of human chorionic gonadotropin (BhCG), and transvaginal three-dimensional ultrasonography. They were also tested for 75 g oral glucose tolerance, thyroid functions, anti-cardiolipin antibodies (IgG/IgM), lupus anticoagulant, anti-thrombin III, protein S, and protein C to rule out glucose intolerance, endocrine dyscrasia, thrombophilia factors, urogenital tumor, and congenital reproductive syste.