Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis

Ruggeri, Rosaria M.; Vicchio, Teresa Manuela; Cristani, Mariateresa; Certo, Rosaria; Caccamo, Daniela; Alibrandi, Angela; Giovinazzo, Salvatore; Saija, Antonella; Campennì, Alfredo; Trimarchi, Francesco; Gangemi, Sebastiano

doi:10.1089/thy.2015.0592

Cited by 77 publications

(69 citation statements)

References 43 publications

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“…It has recently been reported that levels of sRAGE are significantly decreased in HT patients and that serum levels of AGEs are inversely correlated with those of sRAGE, a finding that is consistent with the results of the current study. Another study also showed increased expression of AGEs in HT patients, with positive correlations with TPOAb (50). A tendency toward elevated expression of AGEs in hyperthyroidism patients has also been reported, but this was significant only in patients with GD, which is consistent with our results (51).…”

Section: Discussionmentioning

confidence: 92%

Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases

Peng

Wang

et al. 2016

Front. Immunol.

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ObjectiveAutoimmune thyroid disease (AITD) is an organ-specific disorder due to the interplay between environmental and genetic factors. Toll-like receptors (TLRs) are pattern recognition receptors expressed abundantly on monocytes. There is a paucity of data on TLR expression in AITD. The aim of this study was to examine TLR expression, activation, ligands, and downstream signaling adaptors in peripheral blood mononuclear cells (PBMCs) extracted from untreated AITD patients and healthy controls.MethodWe isolated PBMC of 30 healthy controls, 36 patients with untreated Hashimoto’s thyroiditis, and 30 patients with newly onset Graves’ disease. TLR mRNA, protein expression, TLR ligands, and TLR adaptor molecules were measured using real-time PCR, Western blot, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). PBMC was simulated with TLR agonists. The effects of TLR agonists on the viability of human PBMC were evaluated using the MTT assay. The supernatants of cell cultures were measured for the pro-inflammatory cytokines, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-10 by ELISA.ResultsTLR2, TLR3, TLR9, and TLR10 mRNA were significantly increased in AITD patients compared with controls. TLR2, TLR3, TLR9, high mobility group box 1 (HMGB1), and RAGE expression on monocytes was higher in patients than control at baseline and TLR agonists’ stimulation. The release of TNF-α and IL-6 was significantly increased in PBMCs from AITD patients with TLR agonists, while IL-10 was significantly decreased. Downstream targets of TLR, myeloid differentiation factor 88 (MyD88), and myeloid toll/IL-1 receptor-domain containing adaptor-inducing interferon-β were significantly elevated in AITD patients. Levels of TLR2 ligands, HMGB1, and heat shock protein 60 were significantly elevated in AITD patients compared with those in controls and positively correlated with TgAb and TPOAb, while sRAGE concentration was significantly decreased in AITD patients.ConclusionThis work is the first to show that TLR2, TLR3, and TLR9 expression and activation are elevated in the PBMCs of patients with AITD and TLRs may participate in the pathogenesis of AITD.

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Section: Discussionmentioning

confidence: 92%

Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases

Peng

Wang

et al. 2016

Front. Immunol.

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“…Loss of balance between antioxidant defence mechanisms and overproduction of free radicals also correlated with thyroid dysfunction. 38 Considering all the previous data, we can speculate that a proinflammatory microenvironment and oxidative stress in euthyroid postmenopausal women with AITD/positive TPOAb constitutes the mechanism underlying impaired bone quality and increased risk of fracture. Our results additionally indicate that the impact of TPOAb on bone quality becomes less important when TSH rises above the upper reference range and, furthermore, that elevated TSH increases the risk of any fracture in the future (Table 4, Figure1).…”

Section: Discussionmentioning

confidence: 77%

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Polovina

Miljić

Zivojinović³

et al. 2017

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ObJeCTIVe: Skeletal development, linear growth, cartilage biology and bone turnover are highly dependent on the activity of thyroid hormones. Thyroid dysfunction affects the skeleton, and autoimmune thyroid disease, manifesting as a chronic inflammatory condition, may be an important contributing factor to impaired bone quality in these patients. MATeRIAlS AND MeTHODS: Measurement of TSH, FT4, TPOAb and bone mineral density and FRAX score calculations were performed in 189 postmenopausal women (110 euthyroid women and 79 women diagnosed with subclinical hypothyroidism) divided into subgroups according to the presence of TPOAb. ReSUlTS: In multivariate logistic regression analysis only TPOAb were found to be significantly related to fracture, independently of TSH values (p=0.018; OR=7.800; 95% CI 1.424-42.721). Lower bone mineral density and FRAX score for hip and for major osteoporotic fractures were associated with the presence of TPOAb in euthyroid postmenopausal women in an unadjusted logistic regression model, as well as in a model adjusted for age, bMI and smoking. TSH was a better predictive factor for fractures in women with subclinical hypothyroidism (FRAX main p <0.001; 95% CI for SE 0.858-0.959 and FRAX hip p <0.001; 95% CI for SE 0.628-0.854). CONCLUSION: Autoimmune thyroid disease is associated with decreased bone mineral density at both spine and hip and risk of future fracture incidence in euthyroid postmenopausal women. Presence of TPOAb is a potential marker of higher fracture risk in these patients. However, in subclinical hypothyroidism, TSH is a better indicator of future fragility fractures than TPOAb.

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“…Anti-TPO antibodies are more common than anti-Tg antibodies and more indicative for thyroid disease (21). Anti-TPO antibodies are inductors of oxidative stress evidenced by decreased antioxidant potential, advanced glycosylation products and oxygen metabolites in blood (27). However, their contribution to thyroid damage compared to T cell and cytokine-mediated apoptosis is minor (28).…”

Section: Factors Linked To Thyroid Autoimmunitymentioning

confidence: 99%

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

2017

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Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis.

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Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis

Cited by 77 publications

References 43 publications

Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases

Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases

The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

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