Selenium (Se) is an essential trace element in human. Recent studies of Se supplementation on the effect of Hashimoto’s thyroiditis (HT) have been reported, but the exact benefit is unclear as well as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of Se supplement in patients with HT, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized‑controlled study was performed in patients with HT assigned to two groups. Se‐treated group (n = 43) received selenious yeast tablet (SYT) for 6 months, whereas no treatment in control group (n = 47). The primary outcome is the change of thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb). Second, thyroid function, urinary iodine, Se, Glutathione peroxidase3 (GPx3), and Selenoprotein P1 (SePP1) levels were measured during the SYT treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs, and secreting Tregs, as well as Helios and PD‐1 expression on these cells were also detected. The results showed that SYT treatment significantly decreased TPOAb, TGAb, and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3, and SePP1, compared with the control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in the Se‐treated group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells.

Hashimoto thyroiditis (HT) is an autoimmune disease that presumably arises consequent to loss of immune tolerance to autoantigen in thyroid. Regulatory T cells (Tregs) are considered to play a vital role in maintaining the immune balance, as they own intensive suppressive function. This study was undertaken to analyze numbers of Tregs and their expressions of Helios and PD-1 in HT patients. It also aimed to explore the relationship of these with thyroid function and specific autoantibodies. Peripheral blood mononuclear cells (PBMCs) were extracted from blood of 20 healthy controls (HC) and 42 HT patients with varying thyroid functions (10 overt hypothyroidism, 12 subclinical hypothyroidism, and 20 euthyroidism). We performed flow cytometry analysis in PBMCs to detect CD4⁺CD25⁺Foxp3⁺Tregs and their subsets, including CD45RO⁺Foxp3high activated Treg cells (aTregs), CD45RO^-Foxp3low resting Tregs cells (rTregs), and CD45RO⁺Foxp3low secreting Treg cells (sTregs), as well as the expression of Helios and PD-1 on these cells. The results showed that the percentage of Tregs, aTregs was significantly lower in HT patients and it showed inverse correlation to thyroid function states, in comparison with these in healthy controls. In addition, patients with HT showed decreased expression of Helios in aTregs, while having increased expression of PD-1 in Tregs and sTregs. The levels of Tregs, aTregs, and Helios expressing aTregs were all negatively correlated with antithyroid antibodies. In conclusion, the deficiency of Tregs frequency and aberrant expressions of Helios and PD-1 may possibly contribute to thyroid immune damage in HT.

Aims: In this article, we conducted an updated meta-analysis with trial sequential analysis (TSA) to refine the associations between three common single nucleotide polymorphisms (SNPs) in the CTLA-4 gene (+49A/G, CT60, and −318C/T) and Hashimoto's thyroiditis (HT). Methods: Statistical association analyses were performed using four genetic models, including the allelic, codominant, dominant, and recessive models with the Revman 5.3, Stata 14.0, and TSA 0.9 software. For quality evaluation, the Newcastle-Ottawa Scale was used. Results: Our meta-analysis included 29 independent studies with low risk of bias that involved 3614 cases and 8839 controls. The pooled results indicated a significant association between the +49A/G polymorphism and an increased risk of HT in all four genetic models. Furthermore, the TSA demonstrated that the evidence of this association was robust and credible. Subgroup analysis revealed a significantly higher risk of HT in Asians compared with Caucasians associated with the +49A/G polymorphism. Surprisingly, in contrast to the results with adults, we did not find any significant association when analyzing the pediatric subgroup. For the CT60 polymorphism, a significant association with risk of HT was detected overall, and subgroup analysis revealed that this association was significant in the Asian subgroup, but not in the Caucasian subgroup. No statistically significant associations were detected in any of the investigated genetic models for the −318C/T polymorphism. However, the results of the TSA suggested that the sample sizes used for the CTLA-4 CT60 and −318C/T SNPs were insufficient. Conclusion: Our meta-analysis showed significant associations between the risk of HT and both the +49A/G and CT60 polymorphisms, but not the −318C/T polymorphism. In addition, the TSA results indicated that CTLA-4 +49A/G should be considered as a biomarker for HT, whereas both the CT60 and −318C/T SNPs warrant confirmation by further studies.

Thyroid stimulating hormone receptor (TSHR) is thought to be a significant candidate for genetic susceptibility to Graves' disease (GD). However, the association between TSHR gene polymorphism and the risk of GD remains controversial. In this study, we investigated the relationship between the two conditions by meta-analysis. We searched all relevant case-control studies in PubMed, Web of Science, CNKI and Wanfang for literature available until May 2015, and chose studies on two single nucleotide polymorphisms (SNPs): rs179247 and rs12101255, within TSHR intron-1. Bias of heterogeneity test among studies was determined by the fixed or random effect pooled measure, and publication bias was examined by modified Begg's and Egger's test. Eight eligible studies with 15 outcomes were involved in this meta-analysis, including 6,976 GD cases and 7,089 controls from China, Japan, Poland, UK and Brazil. Pooled odds ratios (ORs) for allelic comparisons showed that both TSHR rs179247A/G and rs12101255T/C polymorphism had significant association with GD (OR=1.422, 95%CI=1.353-1.495, P<0.001, Pheterogeneity=0.448; OR=1.502, 95%CI: 1.410-1.600, P<0.001, Pheterogeneity=0.642), and the associations were the same under dominant, recessive and co-dominant models. In subgroup analyses, the conclusions are also consistent with all those in Asian, European and South America subgroups (P<0.001). Our meta-analysis revealed a significant association between TSHR rs179247A/G and rs12101255T/C polymorphism with GD in five different populations from Asia, Europe and South America. Further studies are needed in other ethnic backgrounds to independently confirm our findings.