The expression of microvesicles in the blood of patients with<scp>G</scp>raves' disease and its relationship to treatment

Mobarrez, Fariborz; Abraham-Nordling, Mirna; Aguilera-Gatica, Katherina; Friberg, Inger; Antovič, Aleksandra; Pisetsky, David S.; Jörneskog, Gun; Wallén, Håkan

doi:10.1111/cen.12872

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…A previous study has shown that HMGB1 is overexpressed in the thyroid of HT patients, and HMGB1 expression is very low in healthy thyroids (44). Recent results also revealed increased numbers of HMGB1-positive monocytes in GD patients compared to healthy controls; with expression decreased by approximately 50% under antithyroid drug treatment (45). HSP60 is an intracellular chaperone that plays an important role in protein folding and stability.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…In autoimmunity, platelet EVs seem to influence the course of disease, being present in high levels in patients with RA (96–98), SLE (98, 99), Grave's disease (100) and systemic sclerosis (101). In RA, EVs can act through several different pathways, presenting antigens to the immune system, degrading extracellular matrix, carrying miRNA and autoantigens, such as citrullinated proteins, resulting in induction of inflammation, as well as perpetuating it by formation of bioactive immunocomplexes (ICs) (23, 98).…”

Section: Hmbg1 and Autoimmunitymentioning

confidence: 99%

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

et al. 2019

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Although much has been made of the role of HMGB1 acting as an acute damage associated molecular pattern (DAMP) molecule, prompting the response to tissue damage or injury, it is also released at sites of chronic inflammation including sites of infection, autoimmunity, and cancer. As such, the biology is distinguished from homeostasis and acute inflammation by the recruitment and persistence of myeloid derived suppressor cells, T regulatory cells, fibrosis and/or exuberant angiogenesis depending on the antecedents and the other individual inflammatory partners that HMGB1 binds and focuses, including IL-1β, CXCL12/SDF1, LPS, DNA, RNA, and sRAGE. High levels of HMGB1 released into the extracellular milieu and its persistence in the microenvironment can contribute to the pathogenesis of many if not all autoimmune disorders and is a key factor that drives inflammation further and worsens symptoms. HMGB1 is also pivotal in the maintenance of chronic inflammation and a “wound healing” type of immune response that ultimately contributes to the onset of carcinogenesis and tumor progression. Exosomes carrying HMGB1 and other instructive molecules are released and shape the response of various cells in the chronic inflammatory environment. Understanding the defining roles of REDOX, DAMPs and PAMPs, and the host response in chronic inflammation requires an alternative means for positing HMGB1's central role in limiting and focusing inflammation, distinguishing chronic from acute inflammation.

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“…Microvesicles are released into the circulation from multiple cell types during apoptosis and reflect metabolic stress. A very recent case–control study from Sweden investigated the number of microvesicles (i.e., diameter < 1 μm) in the blood of patients with GD, which was seen to be increased in the blood of GD patients compared with healthy controls and to remain elevated after medical therapy, albeit at a lower level [ 80 ]. This concept might as well offer a new biomarker to guide future treatment decisions in patients with GD.…”

Section: Main Textmentioning

confidence: 99%

Is Graves’ disease a primary immunodeficiency? New immunological perspectives on an endocrine disease

Struja

Kutz

Fischli

et al. 2017

BMC Med

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BackgroundUncertainty about factors influencing the susceptibility and triggers for Graves’ disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research.Main textRelevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms “Graves’ Disease” or “Basedow” or “thyrotoxicosis” together with the terms “etiology”, “pathophysiology”, “immunodeficiency”, “causality”, and “autoimmunity”. The terms “orbitopathy”, “ophthalmopathy”, and “amiodarone” were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion.ConclusionsWhile concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves’ disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

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The expression of microvesicles in the blood of patients withGraves' disease and its relationship to treatment

Cited by 14 publications

References 28 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

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

Is Graves’ disease a primary immunodeficiency? New immunological perspectives on an endocrine disease

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