The Role of MIF-173G/C Gene Polymorphism in the Susceptibility of Autoimmune Diseases.

Some certain genetic polymorphisms have been considered to implicate in the pathogenesis and progression of autoimmune diseases and may predispose to an early stage of general autoimmune susceptibility. Recent studies have been conducted to investigate the association between macrophage migration inhibitory factor- (MIF-) 173G/C gene polymorphism and autoimmune diseases; however, the results were not exactly identical. In the present study, a systematic review and meta-analysis of case-control studies was performed to estimate the relationship. A comprehensive search of PubMed, Ebsco, EMbase, WanFang databases and CNKI was done. Odds ratio (ORs) and corresponding 95% confidence intervals (CIs) were combined to pool the effect size. The publication bias was examined by Begg's funnel plots and Egger's test. RevMan 5.3 and STATA 12.0 software were used for statistical processing. 23 papers were included, and the results revealed that MIF-173G/C was significantly associated with an increased risk of autoimmune diseases in five genetic models (recessive genetic model: OR = 1.95, 95% CI: 1.52-2.50; dominant genetic model: OR = 1.35, 95% CI: 1.24-1.46; allele model: OR = 1.32, 95% CI: 1.23-1.41; homozygote model: OR = 1.92, 95% CI: 1.57-2.35; heterozygote model: OR = 4.92, 95% CI: 4.03-6.02), whether in Asia, Europe, or North America. Furthermore, subgroup analysis showed an increasing risk in rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease (CD), atopic dermatitis (AD), Henoch-Schonlein purpura (HSP), and Henoch-Schonlein purpura nephritis (HSPN), but it was not related to the susceptibility of autoimmune hepatitis (AIH). Therefore, it could be considered that MIF-173G/C polymorphism could increase the susceptibility of autoimmune diseases, while there may be the discrepancy of disease entity.

Relationship between the upregulation of Notch1 signaling and the clinical characteristics of patients with papillary thyroid carcinoma in East Asia: a systematic review and meta-analysis.

BACKGROUND: Many studies have aimed to clarify the relationship between Notch1 signaling and papillary thyroid carcinoma (PTC), but the results have been inconsistent to date. In the present study, a systematic review and meta-analysis were performed to analyze the relationship between Notch1 signaling and the clinical characteristics of PTC. METHODS: Literature databases, including PubMed (Medline), Embase and China National Knowledge Infrastructure, were searched for relevant studies from inception to April 2018. A total of five studies, including 421 patients with PTC from China and South Korea, were included in the meta-analysis. RESULTS: The results revealed that the upregulation of Notch1 signaling was positively correlated with lymph node metastasis in patients with PTC (OR = 3.25, 95% CI 1.14-9.23, P = 0.03). Additionally, positive correlations were found between Notch1 signaling and tumor size (OR = 4.34, 95% CI 1.66-11.38, P = 0.003), capsular invasion (OR = 3.49, 95% CI 1.90-6.41, P < 0.0001) and clinical stage of PTC (OR = 2.31, 95% CI 1.05-5.11, P = 0.04). CONCLUSIONS: The Notch1 signaling pathway may play a catalytic role in the progression of PTC, and upregulation of Notch1 signaling may have significant predictive value for the clinical prognosis of PTC.

Macrophage migration inhibitory factor interacting with Th17 cells may be involved in the pathogenesis of autoimmune damage in Hashimoto's thyroiditis.

PURPOSE: To explore the possible role of MIF and Th17 cells in the thyroid-specific autoimmune damage of Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: We enrolled 40 HT patients and 30 healthy controls and divided HT patients into euthyroid subset (n = 22) and subclinical or overt hypothyroidism subset (n = 18). The percentages of Th17 cells and expressions of MIF, interleukin 17A (IL-17A) mRNA in PBMCs, as well as serum concentrations of MIF, and IL-17A, and thyroid functions, and thyroid-specific autoantibodies (TPOAb, TgAb) were detected by flow cytometry, real-time RT-PCR, ELISA, and ECLIA in all subjects. RESULTS: MIF mRNA, IL-17A mRNA expressions and Th17 cells percentages, serum MIF, and IL-17A protein levels were all significantly higher in HT patients, even in euthyroid subgroup. Additionally, the differences became more obvious in dysfunction subgroup. Importantly, both MIF levels and Th17 cells percentage were positively correlated with serum TPOAb, TgAb, and thyrotropin (TSH) levels in HT patients. CONCLUSIONS: These data suggest that MIF and Th17 cells increased dynamically and positively correlated with the markers of thyroid autoimmune damage, which indicated that interaction between MIF and Th17 cells may participate in the pathogenesis and development of thyroid-specific autoimmunity in HT.

The possible role of CD4⁺CD25(high)Foxp3⁺/CD4⁺IL-17A⁺ cell imbalance in the autoimmunity of patients with Hashimoto thyroiditis.

Hashimoto thyroiditis (HT) is a prototypic organ-specific autoimmune thyroid disease, for which the exact etiology remains unclear. The aim of this study was to investigate dynamic changes in regulatory T cell (Treg) and T helper 17 cell (Th17) populations in patients with HT at different stages of thyroid dysfunction, as well as to analyze the possible correlation between the Treg/Th17 cell axis and autoimmune status in HT. We assessed thyroid function and autoantibody serology both in HT patients and in healthy controls (HCs) and divided HT patients into three subgroups according to thyroid function. We then determined the percentages of Treg and Th17 cells in peripheral blood mononuclear cells and analyzed mRNA expression of the Treg and Th17 cell-defining transcription factors Foxp3 and RORγt. In addition, serum levels of TGF-ß and IL-17A were assessed. We found that the percentage of Treg cells, Foxp3 mRNA levels, and the ratio of Treg/Th17 cells were all significantly lower in HT patients, while Th17 cell percentages and RORγt mRNA levels were significantly higher. Interestingly, we also observed significant differences in these measurements between HT patient subgroups. Serum IL-17A levels were markedly increased in HT patients, while serum concentrations of TGF-ß were lower, compared to HCs. The ratio of Treg/Th17 cells was negatively correlated with the levels of serum thyroperoxidase antibody, thyroglobulin antibody, and thyrotropin (TSH) in HT patients. Taken together, our data suggest that the balance between Treg and Th17 cells shifts in favor of Th17 cells during clinical progression of HT, which is negatively correlated with levels of thyroid-specific autoantibodies and TSH, implying that Treg/Th17 cell imbalance may contribute to thyroid damage in HT.

[Changes in the number and distribution of myoepithelial cells during atrophy of rat parotid gland].

OBJECTIVE: To investigate the changes in the number and distribution of myoepithelial cells during atrophy of the rat parotid gland. METHODS: Atrophy of the right parotid was induced by ligating the right stensen duct of rats, histological changes of parotid glands were examined by hematoxylin-eosin (HE) staining during each step of glandular atrophy at the time of 0 (control), 1, 3, 5, 7, 14, 21, 30, 60, 100, and 150 days after ligation. Immunohistochemical labelling was performed to study the changes in number and distribution of myoepithelial cells during atrophy of the rat parotid gland. RESULTS: Histological analysis showed disappearance of the acini at 5 d and gradual decrease and fibrosis of the glandular lobules accompanied by the occurrence of duct-like structures. Quantitative analysis of myoepithelial cells showed significant increase in number up to day 5 after ligation, then followed by gradual increases at a low level, at last it was followed by a rapid decrease after the total number reached the peak in 100 days. In addition, the acini and intercalated ducts were covered by myoepithelial cells ranged from the shape of spindle to stellate during the early phase of atrophy, while spindle-shaped myoepithelial cells were located at the periphery of duct-like structures in the later phase of atrophy. CONCLUSION: Myoepithelial cells proliferated rapidly up to day 5 after ligation, then followed by gradual increase at a low level, at last it was followed by a rapid decrease after the total number reached the peak in 100 days.

[Expression of programmed cell death 5 and apoptosis during atrophy of the parotid gland cells].

OBJECTIVE: To investigate the expression and relationship of programmed cell death 5 (PDCD5) and cell apoptosis in the parotid gland after leading duct ligation in rat and elucidate the role of PDCD5 on the atophy of parotid gland. METHODS: The Wistar rat model of leading duct ligation was established, and the samples of parotid gland were obtained from different time point (0, 1, 3, 5, 7, 14, 21, 30, 60, 90 and 120 d). The expression of PDCD5 protein was examined by immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). RESULTS: The distribution of PDCD5 protein in normal parotid was in cytoplasm with uniformity. The expression of PDCD5 protein was significantly increased and reached the peak at 3 d (1.261 ± 0.048) following main duct ligation. PDCD5 was located both in cytoplasm and nuclear of parotid gland cells. The PDCD5 density in acinar cells was higher than that in duct cells at day 1 and 3 after duct ligation (P < 0.01). The apoptotic cells were obviously upregulated at 3 d after duct ligation. The apoptosis index observed in acinar cells [(21.750 ± 0.119)%] was more than that in duct cells [(5.720 ± 0.205)%]. The difference of apoptosis index between acinar cells and duct cells was statistically significant (P < 0.01). The increased PDCD5 levels were positively correlated with cell apoptosis induced by duct ligation. CONCLUSIONS: The expression of PDCD5 is associated with the atophy of the parotid gland after rat parotid duct ligation, indicating that PDCD5 might play an important role in apoptotic pathways after parotid duct ligation.