The Detection of Serum IgMs to Thyroglobulin in Subacute Thyroiditis Suggests a Protective Role of IgMs in Thyroid Autoimmunity

2020 ◽  
Vol 105 (6) ◽  
pp. e2261-e2270 ◽  
Author(s):  
Debora Ricci ◽  
Alessandro Brancatella ◽  
Michele Marinò ◽  
Mario Rotondi ◽  
Luca Chiovato ◽  
...  
Keyword(s):  
De Novo ◽  
Thyroid Autoimmunity ◽  
High Serum ◽  
Subacute Thyroiditis ◽  
Autoimmune Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Abstract Context The role of serum immunoglobulin (Ig)Ms in autoimmune thyroid diseases is uncertain. Objective We looked for IgMs to thyroglobulin (Tg) in patients with subacute thyroiditis (SAT), which is characterized by high serum Tg levels, the possible de novo appearance of IgGs to Tg (TgAb-IgGs), and no autoimmune sequelae. Main Outcome Measures TgAb-IgMs and TgAb-IgGs were detected by binding to Tg using the enzyme-linked immunosorbent assay (ELISA). The upper reference limit of TgAb-IgMs and TgAb-IgGs was established in 40 normal subjects. We looked for TgAb-IgMs in 16 patients with SAT, 11 with Hashimoto’s thyroiditis (HT), and 8 with Graves’ disease (GD) who were all positive for TgAb-IgGs. IgM binding to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH), and glucagon in ELISA was measured. Inhibition of TgAb-IgMs binding to coated Tg was evaluated by preincubating serum samples or IgG-depleted samples with soluble Tg. Results TgAb-IgMs were positive in 10/16 patients with SAT, 2/11 with HT, and 1/8 with GD. TgAb-IgMs were higher in SAT (0.95; 0.42–1.13) (median; 25th–75th percentiles) than in HT (0.47; 0.45–0.51) and GD patients (0.35; 0.33–0.40) (P < .005 for both). IgM binding of SAT sera to BSA, KLH, and glucagon was significantly lower than Tg. Preincubation with soluble Tg reduced the binding of IgMs to coated Tg by 18.2% for serum samples and by 35.0% and 42.1% for 2 IgG-depleted samples. TgAb-IgM levels were inversely, although nonsignificantly, correlated with Tg concentrations. Conclusions Tg leak associated with thyroid injury induces the production of specific TgAb-IgMs, which, in turn, increases the clearance of Tg and might prevent the establishment of a persistent thyroid autoimmune response.

scholarly journals Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

2019 ◽  
Vol 73 (2) ◽  
pp. 67-77
Author(s):  
Tatjana Zaķe ◽  
Sandra Skuja ◽  
Aivars Lejnieks ◽  
Valērija Groma ◽  
Ilze Konrāde
Keyword(s):  
Thyroid Autoimmunity ◽  
Treg Cells ◽  
Thyroid Diseases ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Th17 Lymphocytes ◽  
Immunological Mechanisms ◽  
Thyroid Autoantigens ◽  
The Impact

Abstract Autoimmune thyroid diseases (AITD) mainly include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.

scholarly journals TGF-β Physiology as a Novel Therapeutic Target Regarding Autoimmune Thyroid Diseases: Where Do We Stand and What to Expect

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 621
Author(s):  
Efstratios Kardalas ◽  
Spyridoula Maraka ◽  
Maria Papagianni ◽  
George Paltoglou ◽  
Charalampos Siristatidis ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Thyroid Autoimmunity ◽  
Treatment Options ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Activation Pathways ◽  
Novel Therapeutic

Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-β, scientific interest was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-β in thyroid autoimmunity. Suggested TGF-β-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmunity. For example, the application of hr-TGF-β can be used to bolster the inhibitory role of TGF-β regarding the development of thyroid diseases, whereas anti-TGF-β antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-β biosynthesis and activation pathways. In conclusion, TGF-β could evolve to a promising, novel therapeutic tool for thyroid autoimmunity.

The role of hereditary and environmental factors in autoimmune thyroid diseases

2012 ◽  
Vol 153 (26) ◽  
pp. 1013-1022 ◽  
Author(s):  
Csaba Balázs
Keyword(s):  
Environmental Factors ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Thyroid Autoimmunity ◽  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Histocompatibility Complex

Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves’ disease to hypothyroidism in Hashimoto’s thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DRβ1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves’ disease and Hashimoto’s thyroiditis, while glutamine at position DRβ1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DRβ1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being presented in vivo and activating T-cells in autoimmune thyroid diseases. Taken together these findings suggest that thyroglobulin 2098, a strong and specific binder to the disease-associated HLA-DRβ1-Arg74, is a major human T-cell epitope and it participates in the pathomechanism of the autoimmune thyroid disease. The exact nature of the role of environmental factors in the autoimmune thyroid disease is still not well known, but the importance of several factors such as iodine, drugs and infections has been reported. Further knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for diagnosis, prevention and treatment. Orv. Hetil., 2012, 153, 1013–1022.

scholarly journals Susceptibility Genes in Thyroid Autoimmunity

2005 ◽  
Vol 12 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Yoshiyuki Ban ◽  
Yaron Tomer
Keyword(s):  
Genetic Susceptibility ◽  
Thyroid Autoimmunity ◽  
Twin Studies ◽  
Epidemiological Data ◽  
Susceptibility Genes ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Genome Screening ◽  
Shared Genetic

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity.

scholarly journals The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

2004 ◽  
pp. 225-234 ◽  
Author(s):  
G Aust ◽  
D Sittig ◽  
L Becherer ◽  
U Anderegg ◽  
A Schutz ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Thyroid Autoimmunity ◽  
Thyroid Tissue ◽  
Mrna Levels ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Lymphocytic Infiltrates ◽  
Secondary Lymphoid Organs

OBJECTIVE: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are characterized by lymphocytic infiltrates partly resembling secondary lymphoid follicles in the thyroid. CXCR5 and its ligand CXCL13 regulate compartmentalization of B- and T-cells in secondary lymphoid organs. The aim of the study was to elucidate the role of this chemokine receptor-ligand pair in thyroid autoimmunity. METHODS: Peripheral blood and thyroid-derived lymphocyte subpopulations were examined by flow cytometry for CXCR5. CXCR5 and CXCL13 cDNA were quantified in thyroid tissues by real-time RT-PCR. RESULTS: We found no differences between the percentages of peripheral blood CXCR5+ T- and B-cells in GD patients (n=10) and healthy controls (n=10). In GD patients, the number of memory CD4+ cells expressing CXCR5 which are functionally characterized as follicular B helper T-cells is higher in thyroid-derived (18+/-3%) compared with peripheral blood T-lymphocytes (8+/-2%). The highest CXCL13 mRNA levels were found in HT (n=2, 86.1+/-1.2 zmol (10(-21) mol) cDNA/PCR) followed by GD tissues (n=16, 9.6+/-3.5). Only low amounts were determined in thyroid autonomy (TA) (n=11) thyroid tissues, irrespective of whether the autonomous nodule (0.5+/-0.1) or the surrounding normal tissue (1.8+/-0.7) had been analyzed. The same differences were found for CXCR5 (HT: 179.1+/-6.8; GD: 17.4+/-10.6; TA(nodule): 0.8+/-0.5; TA(normal): 4.4+/-3.6). In GD, there is a correlation between CXCL13 and CXCR5 mRNA levels and the number of focal lymphocytic infiltrates and germinal centers as well as anti-thyroperoxidase but not anti-TSH receptor autoantibodies. CONCLUSIONS: CXCR5 and CXCL13 play an essential role in maintaining B- and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity.

scholarly journals Serum YKL-40 Levels in Patients with Gastric Cancer

2011 ◽  
Vol 3 ◽  
pp. BIC.S7154 ◽  
Author(s):  
Veyis Itik ◽  
Ozgur Kemik ◽  
Ahu Kemik ◽  
A. Cumhur Dulger ◽  
Aziz Sümer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colorectal Cancers ◽  
Healthy Population ◽  
Serum Samples ◽  
Future Studies ◽  
Male Patients

Aims and background YKL-40 is secreted by several types of tumors. Increased serum YKL-40 levels have been reported in prostate, glioblastoma, breast and colorectal cancers. Determination of YKL-40 levels may serve as a valuable biomarker for the diagnosis and treatment of gastric cancer. The purpose of this study was to determine the serum YKL-40 levels expressed in gastric carcinomas. Methods Between 2009 and 2011, we retrospectively reviewed 100 patients with gastric cancer and compared their serum samples to 75 healthy volunteers. YKL-40 levels were determined by an enzyme-linked immunosorbent assay (ELISA). Results We found significantly higher serum levels of YKL-40 in patients with gastric cancer compared to the healthy population ( P < 0.0001). We also found significant differences in serum YKL-40 levels between female and male patients with gastric cancer ( P < 0.01). Conclusions YKL-40 is over-expressed in gastric cancer, suggesting a more aggressive phenotype. YKL-40 may be a useful serum biomarker for gastric cancer identification, and future studies should focus on the role of YKL-40 in the tumorigenesis of gastric cancer and responsiveness toward treatment.

scholarly journals The role of selenium in the pathogenesis of thyroid disease

2019 ◽  
Vol 14 (4) ◽  
pp. 192-205 ◽  
Author(s):  
Ekaterina A. Troshina ◽  
Evgeniya S. Senyushkina ◽  
Maria A. Terekhova
Keyword(s):  
Immune Response ◽  
Thyroid Disease ◽  
Animal Experiments ◽  
Optimal Level ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Increased Risk ◽  
Combined Deficiency

The past few years have been actively discussing the role of individual macro- and micronutrients as factors regulating the functional activity of organs and systems and reducing the risk of developing a number of diseases, including thyroid diseases. Selenium is one of the most important and intensively studied at present microelements. According to several studies, its low plasma level is associated with an increased risk of developing autoimmune thyroid diseases. In animal experiments, it was shown that a combined deficiency of selenium and iodine leads to more pronounced hypothyroidism than iodine deficiency alone. Some authors believe that cretinism in the newborn is a consequence of the combined deficiency of these two elements in the mother. It is also important that the optimal level of selenium is necessary both to initiate an immune response and to regulate an excessive immune response, as well as chronic inflammation. The review article discusses the relationship between selenium and thyroid pathology, discusses the role of selenium in the physiology of the thyroid gland and in the development of autoimmune diseases. The biochemical aspects of the pathogenesis of thyroid disease are presented.

scholarly journals Serosurvey of bluetongue, caprine arthritis-encephalitis (CAE) and Maedi-Visna in Barbary sheep (Ammotragus lervia) of a southern Brazilian zoo

2018 ◽  
Vol 38 (6) ◽  
pp. 1203-1206
Author(s):  
Vivien M. Morikawa ◽  
Maysa Pellizzaro ◽  
Igor A.D. Paploski ◽  
Mariana Kikuti ◽  
Maria C.C.S.H. Lara ◽  
...  
Keyword(s):  
Enzyme Linked Immunosorbent Assay ◽  
High Morbidity ◽  
Serum Samples ◽  
Agar Gel ◽  
Ammotragus Lervia ◽  
Wildlife Species ◽  
Barbary Sheep ◽  
Visna Virus ◽  
Compulsory Notification

ABSTRACT: Bluetongue (BT) is an infectious and non-contagious disease of compulsory notification which may affect domestic and wild ruminants, transmitted by Culicoides spp. midges. Despite the high morbidity and mortality in sheep, role of wild animals in the BT cycle remains unclear. Caprine arthritis-encephalitis (CAE) and Maedi-Visna virus (MVV) have been reportedly found in goats and sheep, but not described in wildlife species. Accordingly, serum samples from 17 captive Barbary sheep (Ammotragus lervia) from Curitiba zoo, southern Brazil, were tested for bluetongue, caprine arthritis-encephalitis (CAE) and Maedi-Visna viruses by agar gel immunodiffusion (AGID) and enzyme linked immunosorbent assay (ELISA). Antibodies for bluetongue were observed in 6/17 (35.3%) Barbary sheep by AGID test and in 7/17 (41.2%) by ELISA. All samples were negative for the presence of antibodies against caprine arthritis-encephalitis (CAE) and Maedi-Visna viruses. These findings indicate that Barbary sheep may be infected by bluetongue virus and act as wildlife reservoir in both captive and free-range environments.

Serum Calprotectin as a Blood-Based Biomarker for Monitoring Knee Osteoarthritis at Early but Not Late Stages

Cartilage ◽  
2020 ◽  
pp. 194760352096116
Author(s):  
Amin Safa ◽  
Abolfazl Bagherifard ◽  
Hamadalla Hadi Al-Baseesee ◽  
Azade Amini Kadijani ◽  
Hooman Yahyazadeh ◽  
...  
Keyword(s):  
Disease Duration ◽  
Early Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Knee Oa ◽  
Calprotectin Level ◽  
Healthy Control ◽  
Grade Ii ◽  
Late Stages

Objective The identification of early-stage osteoarthritis (OA) is crucial for the deceleration of its progression; however, no reliable biomarker is available for this purpose. The current study aimed to determine the role of serum calprotectin in the detection of early-stage knee OA. Design In a case-control study, serum samples were collected from 84 patients with primary bilateral knee OA and 52 healthy controls. The radiographic grading of knee OA was performed using the Kellgren-Lawrence classification system. Serum concentrations of calprotectin were measured using an enzyme-linked immunosorbent assay. Results The mean serum calprotectin level was 2908 ± 2516 ng/mL in OA patients and 901 ± 875 ng/mL in healthy control subjects ( P < 0.001). Mean serum calprotectin levels were significantly higher in the lower stages of OA: 3740 ± 2728 ng/mL in OA grade I, 3100 ± 2084 ng/mL in OA grade II, 2246 ± 1418 ng/mL in OA grade III, and 2035 ± 765 ng/mL in OA grade IV ( P = 0.047). Serum calprotectin levels were significantly higher in patients with a disease duration <42 months compared with those with a disease duration >42 months ( P = 0.043). Conclusion Serum calprotectin level increases significantly in the early stages of OA and shows a reverse association with disease severity. Therefore, it could be suggested as a promising blood-based marker for early-stage knee OA.

A potential role of TNFR gene polymorphisms in autoimmune thyroid diseases in the Tunisian population

Cytokine ◽  
2008 ◽  
Vol 43 (2) ◽  
pp. 110-113 ◽  
Author(s):  
Maha Kammoun-Krichen ◽  
Noura Bougacha-Elleuch ◽  
Kaouthar Makni ◽  
Mouna Mnif ◽  
Joumaa Jouida ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Potential Role ◽  
Thyroid Diseases ◽  
Tunisian Population ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid
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