Development Of Autoimmune Thyroid Disease Research Articles

Association between allergic rhinitis and development of autoimmune thyroid diseases in Egyptian patients

BackgroundAutoimmune thyroid diseases (AITD) and allergic rhinitis (AR) are prevalent conditions; however, limited research has investigated their association. This study aimed to evaluate whether AR can be considered a risk factor for developing AITD.MethodsA retrospective cohort study analyzed the records of AITD patients who visited Alexandria University Students Hospital between January 2017 and December 2021. The parameters included in the study were thyroid-stimulating hormone (TSH), Free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibodies (TPOAb), thyrotropin receptor antibody (TRAb), eosinophils count, and IgE.ResultsOut of 4,515 eligible patients, 41.7% were diagnosed with AR in addition to AITD. Among the patients with both conditions, 81% were females, their mean age was 45.71 ± 24.14 years, and the mean duration of AITD was 7.32 ± 2.11 years. The Kaplan–Meier analysis revealed that the AR cohort had a higher cumulative incidence of AITD than did the non-AR cohort (log-rank test, p = 0.001). Multivariate-adjusted hazardous ratios showed that patients with AR, female sex, higher white blood cell count, and diagnosis in November had a higher risk of developing AITD.ConclusionsScreening for AITD should be conducted at the time of diagnosis of AR as it could be a risk factor for AITD.

A pilot study of interferon-induced helicase and glutamate decarboxylase gene polymorphism with autoimmune thyroid disease

ABSTRACT Background Numerous genes are involved in immune system modulation, and their polymorphisms may contribute to developing autoimmune disorders. Genetic variation contributes significantly to disease susceptibility to autoimmune thyroid disease (AITD). Objectives This work aims to investigate the role of single-nucleotide polymorphisms (SNPs) of interferon induced with helicase C domain 1 (IFIH1) rs1990760 and glutamate decarboxylase (GAD) rs769404 in AITD development. Methods The study had 330 participants, including 153 cases of Hashimoto’s thyroiditis (HT), 77 cases of Graves’ disease (GD), and 100 healthy controls. All subjects underwent medical history assessment and clinical evaluation. Tests were conducted using real-time PCR, including genotyping of IFIH1 (rs1990760) and GAD (rs769404) via an allele discrimination assay. Results Most patients with AITD were females. About 18.3% of HT cases and 15.6% of GD cases have a positive family history of thyroid disease. A significant statistical difference was observed between AITD cases and control regarding IFIH1 (rs1990760) and GAD (rs769404) gene polymorphism. Moreover, GD patients, HT patients, and the control group showed increased CT and TT alleles in patients compared to those in controls. Conclusion IFIH1 and GAD polymorphisms are involved in AITDs (HT and GD) development and are associated with some clinical presentations. HT and GD cases had a positive family history of thyroid disease. There was a significant statistical difference between AITD cases and control regarding IFIH1 (rs1990760) and GAD (rs769404) gene polymorphism.

Analysis of risk factors for autoimmune thyroid disease based on blood indicators and urinary iodine concentrations.

The aim of this study was to elucidate the relationships between thyroid hormones, lifestyle factors, biochemical markers, and autoimmune thyroid disease (AITD), thereby identifying the factors influencing the development of these diseases. The study encompassed 517 patients with AITD and 549 patients with non-autoimmune thyroid disease. Demographic and clinical data were collected, and various laboratory indicators, including urinary iodine and thyroid hormones, were measured and compared between the groups. Lasso regression was employed to select the independent variables, while logistic regression analysis determined the factors associated with the development of AITD. The prevalence of drinking alcohol history, median urinary iodine, and TSH concentrations proved significantly greater in the AITD group compared to the control group, while FT3 levels demonstrated lower values within the AITD group (p<0.05). Furthermore, there was a significant difference in the distribution of iodine nutrition status between the two groups (p<0.05). Both univariate and multivariate logistic regression analyses revealed significant associations among excessive iodine intake, drinking alcohol history, TSH, FT3, and the development of AITD. Excessive iodine intake and drinking alcohol history are implicated in an augmented risk of developing AITD. The prevention of AITD may necessitate the regular monitoring of TSH and FT3 concentrations.

The Absence of Thyroid-Stimulating Hormone Receptor Expression on Natural Killer T Cells: Implications for the Immune-Endocrine Interaction.

The expression of thyroid-stimulating hormone receptor (TSHR) has been documented on various immune cells, including B lymphocytes, T lymphocytes, Natural Killer (NK) cells, monocytes, and dendritic cells (DCs). Natural Killer T (NKT) cells serve as a crucial link between innate and adaptive immunity, playing significant roles in immunological interactions and autoimmune diseases. The aim of the present study was to evaluate the presence of TSHR on NKT cells. Our research involved patients with thyroid disease, as well as healthy controls. Peripheral blood mononuclear cells (PBMCs) and, thereafter, NKT cells were isolated from 86 patients with benign nodular thyroid disease with and without autoimmune thyroid disease (AITD) (28 and 56 cases, respectively), and TSHR expression was analyzed using fluorescence-activated cell sorting (FACS). In order to confirm the results, the reverse-transcription polymerase chain reaction (RT-PCR) method was used in cells obtained from healthy individuals. Our findings obtained with application of the FACS method revealed that TSHR is not expressed on NKT cells in either AITD or non-AITD patients, though TSHR was detected in the total PBMC population (TSHR+ cells 2.77%). The absence of TSHR on NKT cells was further confirmed with RT-PCR in healthy individuals (p < 0.0001). These results questioned the previously suggested direct influence of NKT cells on AITD development.

Thyroid autoimmunity is associated with dietary fat consumption.

Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.

Iron and ferritin deficiency in women with hypothyroidism and chronic lymphocytic thyroiditis - systematic review.

Iron is one of the essential microelements necessary for maintaining the body's homeostasis. It serves various roles, including being a crucial component in the proper structure of many enzymes and supporting the transport of oxygen and electrons. Its deficiency can lead to anaemia, which is a common clinical condition often associated with thyroid diseases. Iron deficiency is one of the most common nutritional deficiencies, and its prevalence is strongly associated with socioeconomic status. It is the primary cause of anaemia in 42% of children and 50% of women. Importantly, iron deficiency is placed among the top 5 causes of disability in women. Thyroid peroxidase (TPO) is an enzyme essential for the production of thyroid hormones, and iron is a key factor in its proper functioning. Therefore, in the case of iron deficiency, the activity of this enzyme is also reduced. Iron is also a factor that is important in epigenetic modification processes, and its deficiency may contribute to genomic changes potentially promoting the development of autoimmune thyroid diseases. Adequate supplementation in patients with Hashimoto's disease is one of the crucial elements of effective therapy. In addition to iodine, selenium, and magnesium supplementation, attention should be paid to proper iron intake. Iron is an element that is a component of the heme enzyme- thyroid peroxidase, which owes its activity to the binding of haem, and its function is the production of thyroid hormones. Iron can be delivered to the body in haem and non-haem forms. The haem form is found particularly in haemoglobin-rich red meat, but also in eggs, fish, and poultry. On the other hand, non-haem iron can be found in legumes, grains, fruits, and vegetables. Our study aimed to gather and summarise knowledge from scientific literature regarding iron deficiency anaemia and its association with hypothyroidism in women, as well as the possible mechanisms and pathogenesis of these conditions. The paper also aims to highlight that considering the high risk of iron deficiency, assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease.

HLA Class II Allele Groups Involved in Autoimmune Thyroid Diseases: Hashimoto's Thyroiditis and Basedow-Graves Disease.

Autoimmune thyroid diseases (AITD), particularly Hashimoto's thyroiditis (HT) and Basedow-Graves disease (BGD) are diseases of global public health concern, characterized by autoimmune attacks on the thyroid gland, leading to hypothyroidism in HT and hyperthyroidism in BGD. We conducted a study between 2019 and 2021 in northwestern Transylvania (Romania) on patients with HT and with BGD compared to the control group. The aim of the study was to investigate the correlations of HLA class II alleles with AITD by identifying potential genetic susceptibility factors such as HLA-DRB1 and HLA-DQB1 genes in patients diagnosed with HT and BGD. Various molecular biology methods, including SSP-PCR low-resolution and PCR-SSO were employed to analyze DNA samples from patients and control subjects. Our study revealed the influence of the HLA-DRB1*03/*16 genotype as a genetic susceptibility factor for HT, a similar influence regarding BGD being observed for the HLA-DRB1*03 allele group, DRB1*03/*16 genotype, and the DRB1*03/DQB1*06 haplotype. The only protective factor detected in our study was the HLA-DRB1*13 allele group, for both HT and BGD. By elucidating any specific allele or genotype associations that might contribute to the development of AITD, our study can contribute to the prevention and early detection of these diseases.

Genetic and Environmental Factors in Autoimmune Thyroid Disease: Exploring Associations with Selenium Levels and Novel Loci in a Latvian Cohort.

The interplay of genetic, immune and environmental factors strongly contributes to the development of autoimmune thyroid disease (AITD), which can be classified as Graves' disease (GD) or Hashimoto thyroiditis (HT). One of the most studied exogenous factors in the pathogenesis of AITD is selenium, which, in the form of selenoproteins, strengthens the antioxidative defence system of thyroid cells against superoxide production. Furthermore, it modulates inflammatory cytokine release and autoantibody production. The aim of this study was to assess the associations of genetic factors with selenium levels in a cohort of adults with HT and GD and healthy controls from Latvia. A total of 148 GD patients, 102 HT patients and 2442 control participants were included in the study. The genotypes were determined using genome-wide genotyping; imputation was carried out using the TOPMed r2 imputation panel; and association analysis was performed with PLINK v1.90b7. We found three loci associated with GD (LSAMP, HNRNPA3P5, and NTN1) and one locus associated with HT (VAT1L); furthermore, one locus was associated with a serum selenium concentration > 80 µg/L (LINC01544/RNF152/PIGN). The detected associations could be attributed to population-specific effects or unknown stratification in our cohort, and further assessment of these results is required to explain the relationships of genetic traits with AITD and other phenotypes.

Stress-induced urgent conditions in endocrinology

The literature review deals with the influence of chronic stress on the functioning of the endocrine system. The most significant pathological conditions induced by chronic stress are decompensation of carbohydrate metabolism, disorders of the thyroid gland, reproductive system, depressive disorders, electrolyte disorders. The significance of these pathologies is determined by a pronounced decrease in the quality of life, the occurrence of severe complications, and an increase in mortality. The development of hyperglycemia during the acute period of the disease is an established connection between the stress system and glucose homeostasis, which is confirmed by the development of stress hyperglycemia and increased morbidity. Glucocorticoids have a contrainsular effect, and the significance of their impact on carbohydrate metabolism is due to the pleiotropic action: induction of insulin resistance, stimulation of gluconeogenesis, increase in the blood content of glucagon due to dysregulation of its synthesis and secretion. The effects of stress on the thyroid gland are determined by its duration, characterized by the activation of the pituitary-thyroid system in the acute period and its suppression during long-term and chronic stress. The contribution of the stress component and glucocorticoid deficiency to the development of autoimmune thyroid diseases due to the suppression of cellular and strengthening of humoral immunity is discussed. Under conditions of psychological stress, the development of hypothyroidism was noted in emigrants with anxiety-depressive syndrome and insomnia, as evidenced by a decrease in the concentration of thyroid hormones. A decreased thyroid status in these patients is associated with the severity of chronic stress. Research data show that chronic stress can significantly change a person’s thyroid status, leading to the development of triiodothyronine deficiency syndrome and an increase in the production of inactive reverse triiodothyronine, inducing the development of hypothyroidism. It is possible that the pronounced growth of subclinical forms of hypothyroidism, noted in many countries of the world, is a consequence of chronic stress. The hypothalamic-pituitary-adrenal axis is involved in the formation of stress-induced reactions almost immediately after exposure to the stressor. Stress-induced changes in the endocrine system arise and develop in close connection, forming a vicious circle of pathological changes and emergencies.

A Flexible Mouse Model of Autoimmune Thyroiditis Induced by Immunization with an Adenovirus Containing Full-Length Thyroglobulin cDNA.

The main challenge in the "post-GWAS" era is to determine the functional meaning of genetic variants and their contribution to disease pathogenesis. Development of suitable mouse models is critical because disease susceptibility is triggered by complex interactions between genetic, epigenetic, and environmental factors that cannot be modeled by in vitro models. Thyroglobulin (TG) is a key gene for autoimmune thyroid disease (AITD) and several single nucleotide polymorphisms (SNPs) in the TG coding region have been associated with AITD. The classical model of experimental autoimmune thyroiditis (EAT), based on immunization of genetically susceptible mouse strains with purified TG protein in adjuvant, does not allow testing the impact of TG sequence variants on the development of autoimmune thyroiditis. Here we describe a protocol for the induction of EAT by immunization of mice susceptible to thyroiditis with an adenovirus vector carrying full-length human TG cDNA (Ad-TG EAT). We also provide support protocols for evaluation of autoimmune thyroiditis including serological assessment of TG antibodies, in vitro splenocyte proliferation assay and cytokines secretion, thyroid histology, and evaluation of thyroid lymphocytic infiltration by immunostaining. This protocol for EAT induction allows manipulation of the TG cDNA to introduce variants associated with AITD, enabling the testing of the functional effects of susceptible variants and their haplotypes on the immunogenicity of TG. Furthermore, the Ad-TG EAT mouse model is a valuable model for studying the interactions of the TG variants with non-genetic factors influencing AITD development (e.g., cytokines, iodine exposure) or with variants of other susceptible genes (e.g., HLA-DRβ1). © 2024 Wiley Periodicals LLC. Basic Protocol: Development of a mouse model of autoimmune thyroiditis induced by immunization with adenovirus containing full-length thyroglobulin cDNA Support Protocol 1: Splenocytes isolation Support Protocol 2: T cell stimulation and carboxyfluorescein diacetate succinimidyl ester (CFSE) based cell proliferation assay Support Protocol 3: Cytokine assays: measuring levels of interferon gamma (IFNγ) and interleukins IL-2, IL-4, and IL-10 in splenocyte supernatants Support Protocol 4: Evaluating thyroid histology and infiltration with immune cells: hematoxylin-eosin staining of mice thyroid glands Support Protocol 5: Immunohistochemistry of thyroid tissues: Immunofluorescence protocol of paraffin-embedded thyroid sections Support Protocol 6: Anti-thyroglobulin antibody measurement in mice sera by enzyme-linked immunosorbent assay (ELISA).

Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study.

Dyslipidemia has been implicated in the pathogenesis of several diseases, including thyroid dysfunction and immune disorders. However, whether circulating lipids and long-term use of lipid-lowering drugs influence the development of autoimmune thyroid disease (AITD) remains unclear. This study aims to evaluate the effects of lipid-lowering drugs on AITD and explore their potential mechanisms. Two-sample and two-step Mendelian randomization (MR) studies were performed to assess the causal relationships between circulating lipids (LDL-C, TC, TG, and ApoB) and seven lipid-lowering drug targets (ApoB, CETP, HMGCR, LDLR, NPC1L1, PCSK9, and PPARα) with AITD. Mediation analyses were conducted to explore potential mediating factors. There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD (p > 0.05). ApoB inhibition is related to a reduced risk of autoimmune thyroiditis (AT) (OR = 0.462, p= 0.046), while PCSK9 inhibition is related to reduced Graves' disease (GD) risk (OR = 0. 551, p = 0.033). Moreover, PCSK9 inhibition (OR = 0.735, p = 0.003), LDLR inhibition (OR = 0.779, p = 0.027), and NPC1L1 inhibition (OR = 0.599, p = 0.016) reduced the risk of autoimmune hypothyroidism (AIH). Mediation analysis showed that NPC1L1 inhibition and PCSK9 inhibition exerted effects on AIH through IL-4 and FGF-19 levels. And the effect of PCSK9 inhibition on GD through TNF-β levels. There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD. Lipid-lowering drug target gene inhibitors reduced the AITD risk by modulating inflammatory factors.

Impact of Helicobacter pylori virulence on development of autoimmune thyroid diseases

Abstract Background: H. pylori infection has been linked in some controversial studies to the existence of extra-gastrointestinal disorders like autoimmune thyroid disease (AITD). Objective: The study aimed to investigate the impact of the H.pylori virulence factor on progression of autoimmune thyroid disease. Materials and Methods: The study carried out on 90 patients (male and female) with thyroid disorders, and 50 healthy individuals as a control group. Venous blood samples were drawn from all participants, serum obtained after centrifugation and kept in in a labeled Eppendorf tube then stored at -20°C till used in biochemical and immunological assays including: estimation of anti H.pylori IgG to investigate H.pylori infection and detection anti-cag-A IgG titer by ELISA method, while measurement of (T3), (T4), (TSH) and (ATPO) by (e601 cobas) automated immunoassay analyzer. Results: The results of the study recorded a significant increase in mean of TSH concentration (P &lt; 0.01) in patients group particularly in hypothyroidism patients, and a significant increase recorded (P &lt; 0.01) in patients according ATPO level in comparison to control group. On other hand the highest prevalence of H.pylori IgG positive (84%) occur in autoimmune thyroid diseases (AITD) group followed by (63%) for non-AITD while (56%) occur in control group. The results also recorded a highly significant increase in titer of H.pylori IgG (P &lt; 0.01) in patient group as compared to control group, the proportion of female was significantly higher in AITD group (75%), however, there was a significant increase (P &lt; 0.01) in the level of anti-cag IgG in patients as compared to control group, The ratio of infection with H.pylori was greater in the Hashimoto’s thyroiditis group (85.2%) than in the Graves’ disease group (82.4%). Conclusion: our findings state that H. pylori by expressing Cag A may have an impact on the development of autoimmunity thyroiditis.

Exploring the role of gut microbiota in autoimmune thyroid disorders: a systematic review and meta-analysis.

Autoimmune thyroid diseases (AITDs) are characterized by unique immune responses against thyroid antigens and persist over time. The most common types of AITDs are Graves&apos; disease (GD) and Hashimoto&apos;s thyroiditis (HT). There is mounting evidence that changes in the microbiota may play a role in the onset and development of AITDs. The purpose of this comprehensive literature study was to answer the following query: Is there a difference in microbiota in those who have AITDs? According to the standards set out by the PRISMA statement, 16 studies met the requirements for inclusion after being screened for eligibility. The Simpson index was the only diversity measure shown to be considerably lower in patients with GD compared to healthy participants, whereas all other indices were found to be significantly greater in patients with HT. The latter group, however, showed a greater relative abundance of Bacteroidetes and Actinobacteria at the phylum level, and consequently of Prevotella and Bifidobacterium at the genus level. The strongest positive and negative relationships were seen for thyroid peroxidase antibodies and bacterial load. Overall, both GD and HT patients showed significant changes in the gut microbiota&apos;s diversity and composition. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432455.

Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases.

Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the work of many organs and systems of the body, including the immune system and the thyroid gland, and a violation of their supply can be the cause of pathological changes in them. In pathology, the interaction between thyroid hormones (TG), minerals and the immune system is disturbed. The review of the literature examines the immunomodulatory role of TG, minerals, their properties, and their participation in the pathogenesis of autoimmune thyroid diseases (AITD). The study of the relationship between the excess or deficiency of minerals and AITD is described. The basis of the development of AITD - Hashimoto's thyroiditis (HT), Graves' disease (GD), Graves' ophthalmopathy (GO) is the loss of immune tolerance to thyroid antigens - thyroid peroxidase (TPO), thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R). Immune-mediated mechanisms - production of autoantibodies to thyroid antigens and lymphocytic thyroid infiltration - are involved in the pathogenesis of AITD. Insufficiency of regulatory T cells (Treg) and regulatory B cells (Breg), imbalance between Th17-lymphocytes and Treg-lymphocytes, abnormal production of pro-inflammatory cytokines has a significant influence on the progression of AITD. With AITD, the balance between oxidants and antioxidants is disturbed and oxidative stress (OS) occurs. The lack of modern effective pharmacological therapy of AITD prompted us to consider the mechanisms of influence, possibilities of immunocorrection of pathogenetic factors using TG, micro/macronutrients. In order to develop a more effective treatment strategy, as well as approaches to prevention, a critical analysis of the ways of immunotherapeutic use of dietary supplements of I, Se, Zn, Mg and other minerals in AITD was carried out.

COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1β, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.

Potential role of latent toxoplasmosis in inducing thyroid disorders with relevance to autoimmune thyroid disease and interleukin-33 level during pregnancy

Background and Aim: Latent toxoplasmosis is the most frequently occurring parasitic infection worldwide, which causes hormonal and behavioral changes that seriously affect pregnant women. It has also been linked to several autoimmune diseases, including autoimmune thyroid disease (AITD). This study aimed to investigate the association between Toxoplasma gondii seropositivity and thyroid dysfunction, considering the impact of latent toxoplasmosis on the prevalence of maternal AITD and interleukin-33 (IL-33) levels in infected and non-infected pregnant women. Materials and Methods: We conducted a cross-sectional study on 400 pregnant women aged 15–50 in the 8th–36th gestational week. Toxoplasma status was confirmed by detecting anti-Toxoplasma immunoglobulin (Ig)G antibodies. Recent and past chronic toxoplasmosis status was differentiated using the Toxoplasma IgG avidity test. Free triiodothyronine (FT3), free thyroxine, and thyroid-stimulating hormone (TSH) levels were determined to evaluate thyroid disorders. Antibodies against thyroid peroxidase, thyroglobulin, and TSH receptor were assessed to distinguish patients with autoimmune thyroid disorders from those with other thyroid diseases. We divided the subjects into four groups (Toxo+ and abnormal hormone level, Toxo– and normal hormone level, Toxo+ and normal hormone level, and Toxo– and abnormal hormone level) and evaluated their IL-33 levels to investigate its role during the infection. All the tests were performed using the enzyme-linked immunosorbent assay. Results: The results showed that (205/400, 51.2%) samples were seropositive for anti-Toxoplasma IgG antibodies. Of these, (25/205, 12.2%) and (180/195, 87.8%) had recent and past chronic infections, respectively. High infection rates were reported among rural dwellers (150/400, 37.5%) and those in their 3rd trimester (110/400, 27.5%). Of the 205 seropositive patients, (131/205, 63.9%) had thyroid disorders, among which (69/205, 33.7%) and (119/205, 58.0%) had abnormal FT3 and TSH hormone levels, respectively. In contrast, out of 195 Toxoplasma seronegative samples, (99/195, 50.8%) had thyroid disorders; (48/195, 24.6%) and (90/195, 46.2%) had abnormal FT3 and TSH hormone levels, respectively. Groups with abnormal FT3 and TSH levels had significantly higher seropositive anti-toxoplasma IgG antibodies (p = 0.01). Women with seropositive anti-Toxoplasma IgG antibodies had a high hypothyroidism rate (115/205, 56.1%) compared with those with seronegative anti-Toxoplasma IgG antibodies (86/195, 44.1%). We found an association between toxoplasmosis and thyroid status (p &lt; 0.05). Out of 400 samples, 85 (85/400, 21.25%) had AITD. Further, (58/205, 28.3%) of women with seropositive anti-toxoplasma IgG antibodies had AITD compared to (27/195, 13.85%) in the seronegative ones. We found a significant association between toxoplasmosis and AITD (p &lt; 0.05). The IL-33 level was highest in the Toxo+ and abnormal hormone level group (210.86 ± 44.39 pg/mL) and lowest in the Toxo-and normal hormone level group (22.27 ± 8.41 pg/mL). Conclusion: Our results suggest that latent toxoplasmosis was significantly associated with thyroid hormone secretion, which might stimulate the immune system, leading to the development of AITD among pregnant women. Furthermore, the T. gondii seroprevalence was positively correlated with pregnant patients who were rural dwellers and in their 3rd trimester. Keywords: autoimmune thyroiditis disease, interleukin-33, pregnancy, thyroid hormones, toxoplasmosis.

Exposure of Akwesasne Mohawk women to polychlorinated biphenyls and hexachlorobenzene is associated with increased serum levels of thyroid peroxidase autoantibodies

ABSTRACT Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and dichlorodiphenyltrichloroethane (p,p’-DDT) were reported to influence immunological activity. As endocrine-disrupting chemicals (EDC), these pollutants may disrupt normal thyroid function and act as catalysts for development of autoimmune thyroid disease by directly and indirectly affecting levels of thyroid peroxidase antibodies (TPOAbs). Native American communities are disproportionately exposed to harmful toxicants and are at an increased risk of developing an autoimmune disease. The aim of this study was to determine the association between POPs and TPOAbs in serum obtained from Native American women. This assessment was used to measure whether increased risk of autoimmune thyroid disease occurred as a result of exposure to POPs. Data were collected from 183 Akwesasne Mohawk women, 21–38 years of age, between 2009 and 2013. Multivariate analyses were conducted to determine the association between toxicant exposure and levels of TPOAbs. In multiple logistic regression analyses, exposure to PCB congener 33 was related to elevated risk of individuals possessing above normal levels of TPOAbs. Further, HCB was associated with more than 2-fold higher risk of possessing above normal levels of TPOAbs compared to women with normal levels of TPOAbs. p,p’-DDE was not associated with TPOAb levels within this study. Exposure to PCB congener 33 and HCB was correlated with above normal levels of TPOAbs, a marker of autoimmune thyroid disease. Additional investigations are needed to establish the causes and factors surrounding autoimmune thyroid disease which are multiple and complex.

TPO gene rs2071400 polymorphisms as an independent risk factor for hypothyroidism in Iraqi patients

Introduction and Aim: Thyroid peroxidase (TPO) is a thyroid-specific antigen, and the presence of TPO antibodies is known to be associated with developing hypothyroidism. In this study we aimed to investigate the genotypes prevalent for the SNP rs2071400 of the TPO gene and its association to the development of autoimmune thyroid disease. Materials and Methods: This study involved 43 patients with hypothyroidism and 44 healthy controls. Genotyping of the TPO SNP rs2071400 (C/T) was undertaken using Quantitative Real-Time Polymerase Chain Reaction using the TaqMan® Assay. Data obtained was subjected to statistical analysis using the SPSS 25 software Results: TPO rs2071400 T carriers (CT + TT genotypes) were more frequent in patients with hypothyroidism compared with healthy control (P=0.0006), with an adjusted odds ratio of 8.0. Serum levels of Anti-TPOAb were also significantly higher in hypothyroid patients. There was no significant correlation between rs2071400 T mutation and the presence of high Anti-TPOAb. Conclusion: Study revealed TPO rs2071400 polymorphism to be an independent risk factor for developing hypothyroidism in those with or without high serum levels of TPOAb.

COVID-19 and the possible development of autoimmune thyroid diseases

In the midst of continuing coronavirus infection (COVID-19) there has been an increase in the incidence of various autoimmune pathologies. Particular attention to the potential relationship between coronavirus infection and autoimmune diseases is attracted by the positive therapeutic effect of the treatment of severe forms of COVID-19 with drugs used in the treatment of rheumatologically diseases.The results of the study should be the starting point for understanding the mechanisms of possible breakdown of immunological tolerance and the development of autoimmune thyroid diseases.AIM: To assess the risks of developing autoimmune thyroid disease after COVID-19, and to investigate the effect of therapy in the acute period on the possible development of autoimmune thyroid diseases.MATERIALS AND METHODS: This prospective comparative study included patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia (n=41). Patients with COVID-19 were divided into two subgroups: a subgroup of patients who received tocilizumab therapy in acute period (n=10), the second subgroup of patients who received symptomatic therapy during the acute period COVID-19 (n=31).To assess the functional status of the thyroid gland all patients underwent observation of the thyroid-stimulating hormone (TSH), free triiodothyronine (T3f), free thyroxine (T4f), antibodies to thyroperoxidase (Ab-TPO) and antibodies to the TSH receptor (Ab-recTSH).The concentrations of 27 signaling molecules in the blood serum were assessed by the technology of multiplex flow immunoassay using the Bio-Plex Pro Human Cytokine 27-plex Assay kit of cytokines and chemokines: interleukins-1b, -1ra, -2, 4-10, -12, -13, -15, -17 (IL-1b, IL-1ra, IL-2, IL - 4-10, IL-12, IL-13, IL-15, IL-17), Eotaxin, fibroblast growth factor (FGF), granulocyte- macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G -CSF), interferon-gamma (IFN-g), IFNγ-inducible protein 10 (IP-10), monocyte chemotactic protein-1 (MCP-1), also known as monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein -1 (MIP-1a and -1b), platelet growth factor BB (PDGF-bb), Regulated on Activation Normal T-cell Expressed and Secreted (RANTES), tumor necrosis factor-alpha (TNF-a), vascular endothelial growth factor (VEGF).All patients denied the presence of thyroid diseases, palpation of the thyroid gland revealed nodular formations in 5% of patients, and appropriate recommendations were given to patients.RESULTS: The overt hypothyroidism was detected in 2.4% of patients, subclinical - in 7.3% of patients in six months after the onset of coronavirus infection, and also found increased levels of the Ab-TPO in six months after recovery (p = 0.023 - Wilcoxon test). In the group of patients with increased Ab-TPO levels after COVID-19, statistically significantly high levels of IFN-g (p = 0.007), Eotaxin (p = 0.008) were obtained. An increased Ab-recTSH were revealed in the group of patients with severe COVID-19 who did not receive pathogenetic therapy with tocilizumab in the acute period (p = 0.046 - Mann-Whitney test).CONCLUSION: The results of our study and the scientific work of foreign colleagues demonstrate the potential risks of developing autoimmune thyroid diseases after a coronavirus infection. A close relationship was found between changes in the thyroid profile and hyperactivation of the immune system with hyperproduction of pro-inflammatory interleukins in COVID-19. This statement is confirmed by the revealed overt and subclinical hypothyroidism, as well as an increase in Ab- TPO levels in this group of patients after a coronavirus infection (p = 0.023 - Wilcoxon test) with a simultaneous persistent increased levels of some pro-inflammatory cytokines in dynamics, determined by autoimmune thyroiditis.The hypothesis of thyroid tissue damage by pro-inflammatory cytokines during COVID-19, as well as the hypothesis suggesting a protective effect on the development of autoimmune thyroid diseases by therapy with tocilizumab in the acute period were confirmed by increased levels of Ab-recTSH in patients with severe COVID-19 who did not receive tocilizumab in the acute period (p = 0.046 - Mann-Whitney test).

Stress-Related Immune Response and Selenium Status in Autoimmune Thyroid Disease Patients.

Autoimmune thyroid disease (AITD), including Graves' disease (GD) or Hashimoto's thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT (n = 47), GD (n = 13), and a control group (n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4-12)) than a positive stress level (3 (1-9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: rs = -0.296, p = 0.048, and the GD group between GPx and the negative stress level (rs = -0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events (p = 0.023), the number of major life events in the last 7-12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease.