scholarly journals Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 665 ◽  
Author(s):  
Tiphaine C. Martin ◽  
Kristina M. Ilieva ◽  
Alessia Visconti ◽  
Michelle Beaumont ◽  
Steven J. Kiddle ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Immune Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Altered Expression ◽  
Germline Variants ◽  
Autoimmune Thyroid

The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.

scholarly journals Multi-omic analyses reveal antibody-dependent natural killer cell-mediated cytotoxicity in autoimmune thyroid diseases

2019 ◽  
Author(s):  
Tiphaine C. Martin ◽  
Kristina M. Illieva ◽  
Alessia Visconti ◽  
Michelle Beaumont ◽  
Steven J. Kiddle ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Thyroid Diseases ◽  
Cell Subpopulation ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Core Fucosylation

AbstractThe pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation of peripheral blood mononuclear cells in AITD, correlated with thyroid peroxidase antibody (TPOAb) levels. We hypothesized that deficiency in IgG core fucose enhances antibody-dependent cell-mediated cytotoxicity of thyrocytes by TPOAb, contributing to thyroid autoimmunity. Multi-omic evaluations in 622 individuals (172 with AITD) from the TwinsUK cohort showed decreased IgG core fucosylation levels associated with a subpopulation of natural killer (NK) cells featuring CD335, CD314, and CD158b immunoreceptors, and increased levels of apoptosis-associated Caspase-2 and Interleukin-1α, positively associated with AITD. AITD-associated genetic variants rs1521 and rs3094228 alter expression of thyrocyte ligands of the CD314 and CD158b immunoreceptors on NK cells. The combination of low-core fucose IgG associated with an NK cell subpopulation and genetic variant-promoted ligand activation in thyrocytes may promote antibody-dependent NK cell-mediated cytotoxicity of thyrocytes in AITD.

scholarly journals Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

2005 ◽  
Vol 152 (5) ◽  
pp. 703-712 ◽  
Author(s):  
Sebastiano Bruno Solerte ◽  
Sara Precerutti ◽  
Carmine Gazzaruso ◽  
Eleonora Locatelli ◽  
Mauro Zamboni ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hashimoto’S Thyroiditis ◽  
Nk Cell ◽  
Secretory Activity ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Tnf Α

Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves’ disease, 11 patients with Hashimoto’s thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 × 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-β (IFN-β) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-α (TNF-α) from NK cells. Results: Lower spontaneous, IL-2- and IFN-β-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-α release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-β + DHEAS at different molar concentrations (from 10−8 to 10−5 M/ml/NK cells) promptly normalized NKCC and TNF-α secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases

2002 ◽  
Vol 54 (3) ◽  
pp. 141-157 ◽  
Author(s):  
Thierry Chardès ◽  
Nicolas Chapal ◽  
Damien Bresson ◽  
Cédric Bès ◽  
Véronique Giudicelli ◽  
...  
Keyword(s):  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Genetic Variants in TMEM39A Gene Are Associated with Autoimmune Thyroid Diseases

2019 ◽  
Vol 38 (11) ◽  
pp. 1249-1256
Author(s):  
Qiuming Yao ◽  
Bin Wang ◽  
Qiu Qin ◽  
Xi Jia ◽  
Ling Li ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

scholarly journals The mutual cooperation of blood platelets and lymphocytes in the development of autoimmune thyroid diseases

2018 ◽  
Vol 65 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Małgorzata Tomczyńska ◽  
Joanna Saluk-Bijak
Keyword(s):  
Immune Cell ◽  
Blood Platelets ◽  
Lymphocyte Activation ◽  
Thyroid Diseases ◽  
Specific Cell ◽  
Lymphocyte Function ◽  
Autoimmune Thyroid Diseases ◽  
Mutual Cooperation ◽  
Autoimmune Thyroid ◽  
Cell Functions

Autoimmune thyroid diseases include several distinct clinical entities and mainly concern Graves` disease and Hashimoto's thyroiditis. An incompetent immune response directed against the body’s own tissues and the production of antibodies against specific cell antigens, accompanied by chronic inflammation occur in autoimmune thyroid diseases. The autoimmune process is induced by difficult to identify genetic and environmental factors, and generates the development of concomitant diseases of other systems. The inflammatory mediators, high level of thyroid hormones, lymphocyte activation and other immune cells play an important role in the chronic course of these diseases.  Autoimmune thyroid diseases are caused by disruptions of T-cells and other cells functions. The autoantibodies react with target antigens in different kinds of cells, including blood platelets. The autoimmune processes can cause the increased activity different kinds of cells including blood platelets and lymphocytes. The activity of blood platelets and lymphocytes is reciprocally regulated. It is suggested that blood platelets can influence lymphocyte function by direct contact through the receptors and via soluble mediators. The platelet–immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions.

scholarly journals Prevalence of Thyroid Abnormalities in Thai Patients with Vitiligo

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Vasanop Vachiramon ◽  
Sarawin Harnchoowong ◽  
Woranit Onprasert ◽  
Kumutnart Chanprapaph
Keyword(s):  
Thyroid Function Test ◽  
Female Gender ◽  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Thyroid Antibodies ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Dermatology Clinic ◽  
Thyroid Abnormalities ◽  
Serum Tsh

Background. Vitiligo is an acquired hypopigmentary disorder. The prevalence of vitiligo is 0.1–2% worldwide. Numerous autoimmune diseases are associated with vitiligo, including autoimmune thyroid diseases. The prevalence of thyroid abnormalities is up to 34% in vitiligo patients depending on ethnicities. Objective. This study aims to investigate thyroid abnormalities in Thai patients with vitiligo. Methods. Medical records of vitiligo patients attending outpatient dermatology clinic at a university-based hospital from 2012 to 2016 were retrospectively reviewed. Data regarding vitiligo, clinical features, and autoimmune thyroid laboratory results were retrieved and analyzed. Results. Among 325 vitiligo patients identified, anti-thyroid peroxidase and anti-thyroglobulin were positive in 90 (27.7%) and 63 patients (19.4%), respectively. Positive thyroid antibody was associated with female gender (p<0.001) and vitiliginous hand lesions (p<0.02). Out of 197 patients with complete thyroid function test, the prevalence of autoimmune thyroid diseases (AITD) is 12.7%. Female, nonsegmental type, higher affected area, and the presence of leukotrichia are significantly associated with AITD in vitiligo patients. Conclusions. Prevalence of positive thyroid antibodies and AITD in Thai patients with vitiligo is compatible with previous studies around the world. Screening for AITD with thyroid antibodies and serum TSH is essential for vitiligo patients.

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.

Sign in / Sign up

Export Citation Format

Share Document