scholarly journals Decreased IgG core fucosylation, a player in antibody-dependent cell-mediated cytotoxicity, is associated with autoimmune thyroid diseases

2018 ◽  
Author(s):  
Tiphaine C. Martin ◽  
Mirna Šimurina ◽  
Marta Ząbczyńska ◽  
Marina Martinić Kavur ◽  
Magdalena Rydlewska ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Thyroid Diseases ◽  
Thyroid Peroxidase ◽  
Inverse Association ◽  
Autoimmune Thyroid Diseases ◽  
Peripheral Blood Mononuclear ◽  
Autoimmune Thyroid ◽  
Surface Receptors ◽  
Dependent Cell ◽  
Core Fucosylation

AbstractAutoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins (Igs) and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells (PBMCs) glycosylation with AITD and the influence of genetic background. The study revealed an inverse association of IgG core fucosylation with TPOAb and PBMCs antennary α1,2 fucosylation with AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity (ADCC) associated with TPOAb levels.

scholarly journals Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases

2020 ◽  
Vol 19 (5) ◽  
pp. 774-792 ◽  
Author(s):  
Tiphaine C. Martin ◽  
Mirna Šimurina ◽  
Marta Ząbczyńska ◽  
Marina Martinic Kavur ◽  
Magdalena Rydlewska ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Peripheral Blood Mononuclear ◽  
Autoimmune Thyroid ◽  
Blood Mononuclear Cells ◽  
Dependent Cell ◽  
Core Fucosylation

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels.

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.

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

scholarly journals Imbalance of Th17/Treg in Different Subtypes of Autoimmune Thyroid Diseases

2016 ◽  
Vol 40 (1-2) ◽  
pp. 245-252 ◽  
Author(s):  
Cui Li ◽  
Jianghong Yuan ◽  
Yuan-feng Zhu ◽  
Xiang-ju Yang ◽  
Qiong Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Thyroid Diseases ◽  
Control Group ◽  
Clinical Activity ◽  
Autoimmune Thyroid Diseases ◽  
Foxp3 Mrna ◽  
Autoimmune Thyroid ◽  
Th17 Lymphocytes

Aims: To clarify the imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases (AITDs) including Graves' disease(GD), Hashimoto's thyroiditis(HT) and Graves' ophthalmopathy (GO). Methods: 47 patients with AITD (including 16 GD, 15 HT, and 16 GO) and 12 healthy controls were enrolled in this study. The percentages of Th17 and Treg cells, the ratio of Th17/Treg, as well as their related transcription factors RORγt and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry and real-time quantitative PCR Results: Compared with those in control group, the percentage of CD4+IL-17+T cell(Th17) and the mRNA expression of its transcription factor RORγt were higher in PBMCs of AITDs (P<0.05), particularly in HT subgroup (P<0.01). The percentage of CD4+Foxp3+T (Treg) cells and its transcription factor Foxp3 mRNA were significantly decreased in PBMCs of GD (P<0.05). In addition, the ratio of Th17/Treg was elevated in AITD group and GO subgroup (P<0.01). In GO subgroup, the patients with clinical activity score (CAS) above 4.5 had higher percentages of Th17 than those with CAS ranging from 3 to 4.5 (P<0.05). Conclusion: Increased Th17 lymphocytes may play a more important role in the pathogenesis of HT and GO while decreased Treg may be greatly involved in GD.

Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases

2017 ◽  
Vol 55 (5) ◽  
Author(s):  
Hiroshi Otsu ◽  
Mikio Watanabe ◽  
Naoya Inoue ◽  
Ryota Masutani ◽  
Yoshinori Iwatani
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Intraindividual Variation ◽  
Autoimmune Thyroid Diseases ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Autoimmune Thyroid ◽  
Blood Mononuclear Cells

AbstractBackground:microRNAs (miRNAs) circulate in the blood and negatively regulate the expression of mRNAs. Some miRNAs are associated with the development of autoimmune thyroid diseases (AITD); however, there are few reports on the association between miRNA expression and the pathogenesis of AITD or the physiological variations of circulating miRNAs, which are important to examine as biomarkers.Methods:We examined the circadian and day-to-day variations in the expression levels of 5 miRNAs (miR-125a, miR-146a, miR-155, let-7e and miR-106a) in plasma and peripheral blood mononuclear cells (PBMC). We also analysed the expression levels of two of these miRNAs (miR-146a and miR-155) in 20 healthy controls, 60 Graves’ disease (GD) patients and 50 Hashimoto’s disease (HD) patients.Results:For each miRNA, we observed wide intraindividual variation [coefficient of variation value (CV): 70%–100%] compared to measurement error (CV: 20%–40%). In patients with AITD, HD, GD in remission and mild HD, the expression levels of miR-146a in PBMC were increased 296%, 328%, 348% and 464% above the levels in healthy controls, respectively (p=0.0443 and p=0.0273, p=0.0267 and p=0.0052, respectively). In severe HD, the expression level of miR-155 in plasma was increased to 347% of that in healthy controls (p=0.0256).Conclusions:The expression levels of miRNAs in plasma and PBMC showed wide intraindividual variation. In addition, miR-146a may be associated with the development of AITD.

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.

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