Thyroid Antigens Research Articles

Expression of thyroid antigens in the female reproductive system.

Thyroid autoimmunity (TAI) has been linked to fertility disorders and pregnancy complications, even in euthyroid women. However, the exact pathophysiological mechanism underlying this association is not fully understood. This study seeks to investigate the expression of thyroid antigens within the human female reproductive system, potentially identifying targets for thyroid antibodies. Human biopsies of endometrium and follicular granulosa cells were collected and thyroperoxidase (TPO) and thyroglobulin (TG) expression was evaluated in these tissues by immunohistochemistry. Results showed, for the first time, the expression of TG protein and confirmed the presence of thyroid TPO in human endometrium and granulosa cells. Results suggest that TPO antibodies (TPOAbs) and TG antibodies (TGAbs) could interact with TPO and TG expressed in the reproductive system in patients with positive thyroid antibodies, thereby disrupting the function of TPO and TG and generating an inflammatory response, leading to fertility disorders and pregnancy complications.

The immune response formed by the introduction of a DNA vector containing a cDNA fragment of the human thyroid-stimulating hormone receptor gene into transgenic mice

The number of patients with autoimmune thyroid diseases (Graves’disease, Hashimoto’sthyroiditis) is increasing globally. The most important part in the diagnosis of Graves’ disease (GD) is the detection of autoantibodies to the thyrotropin receptor (TSHR) in Graves’ patients’ sera. For the differential diagnosis of antibodies to thyroid antigens, it is promising to use tests based on monoclonal antibodies to TSHR, which can be obtained not only as a result of immunization with native or recombinant TSHR protein, but also through DNA immunization with genetically engineered constructs containing fragments of the TSHR gene. Based on mRNA we isolated from the thyroid tissue in GD, a number of fragments of the thyrotropin receptor gene were cloned, suitable for DNA immunization of animals. The purpose of this work is to evaluate the immunogenic properties of one of the constructed vectors, pVAX1-TSHR (1160), in a mouse model. The successful inclusion of the extracellular domain gene fragment of the human TSHR (1160), which was transfected into CHO cells as a part of the pVAX1 vector was confirmed by immunoblotting and ELISA. The immune response formed to the injection of the pVAX1 vector into BALB/c mice, containing a fragment of the human TSHR gene, was detected in different versions of ELISA. Immunization of animals with the DNA vector pVAX1-TSHR according to an experimentally selected scheme was effective for the formation of mouse splenocytes, secreting antibodies to TSHR, which were used for successful hybridization. This was confirmed by the results of determining antibody production to TSHR in murine blood sera. The level of antibody production remained high (titer more than 1:10.000) at the 8th week of the experiment. As a result of selection of individual clones according to the criteria of proliferative activity and stability of antibody production, the most stable cultures secreting mAbs against TSHR were selected.

Content of macro- and microelements in rats with experimental autoimmune thyroiditis and under the influence of lemna minor

The aim was to study the effect of aqueous extract and 30 % alcohol tincture of Lemna minor frond (AELM and TLM) on the content of macro- and microelements in rats with experimental autoimmune thyroiditis. Materials and methods. The effect of AELM and TLM was studied in a model of experimental autoimmune thyroiditis in rats, induced by immunization with human thyroid antigen. The serum levels of total thyroxine, total triiodothyronine, antibodies to thyroglobulin, antibodies to thyroperoxidase, and concentrations of macro- and microelements were studied. Results. The development of experimental autoimmune thyroiditis led to a decrease in the content of total thyroxine and antibodies to thyroperoxidase in the blood serum, an increase in the content of antibodies to thyroglobulin and a decrease in the concentrations of sodium, chlorine, potassium phosphorus, zinc, copper, iron and magnesium. It was found that the use of AELM and TLM against the background of autoimmune thyroiditis led to the restoration of T4 and elemental balance in rats, which was manifested in an increase in the content of sodium, chlorine, phosphorus, magnesium, zinc, iron, copper and calcium in the blood serum. It was also shown that TLM had a more powerful effect on the normalisation of the content of such elements as chlorine, potassium, copper and zinc. The obtained effect of AELM and TLM on the content of macro- and microelements in the blood serum of animals with experimental AIT can be explained by their positive effect on the functional activity of the thyroid gland. The studied extract and tincture may also affect other physiological and biochemical processes due to the content of macro- and microelements and other biologically active substances, which requires further research. Conclusions. Administration of AELM and TLM to rats with experimental AIT contributed to lowering the level of Anti-TG and restoring the thyroid and elemental status in the animals' blood serum. The obtained research data allow us to recommend AELM and TLM as a regulator of the elemental status of the body in case of changes in thyroid function

Graves Disease - A Comprehensive Review

Graves Disease (GD) is an inflammatory disorder that often results in hyperthyroidism. GD is particularly prone to affecting women, African Americans, individuals with pre-existing autoimmune conditions, and first-degree relatives of those with GD. GD presents through a breakdown of immune tolerance against thyroid antigens. This occurs through a multifactorial autoimmune dysfunction of environmental and mainly genetic contribution. Hereditary predisposition accounts for 79% of the GD risk and increases susceptibility to dysfunction by environmental risk factors such as smoking, vitamin D deficiency, and stressful life events. GD is caused by a disruption of the thyroid gland on a molecular level. The disease is characterized by an overstimulation of the thyroid gland causing hyperthyroidism. This issue is caused by thyroid-stimulating immunoglobulin (TSI) synthesized by B cells. These immunoglobulins bind to the TSH receptors on the thyroid gland, activating it and producing an abundance of the thyroid hormones, levothyroxine (T4) and triiodothyronine (T3). The clinical presentation of GD encompasses a diverse array of signs and symptoms, from common manifestations such as palpitations, weight reduction, and exophthalmos, to less conventional presentations like cardiac complications and cholestatic hepatic injury. There are many methods of diagnosis that are used for GD including the gold standard, which tests for TSI and antibodies against the TSH receptor. Other methods include radioactive iodine uptake and CT scans that test for thyroid enlargement and are used to substitute radioactive iodine uptake tests for pregnant women. The three classical treatments for GD are antithyroid drugs, radioiodine treatment, and thyroidectomy. Additional treatments include corticosteroids which are used to decrease exophthalmos. Beta-adrenergic blockers are used for tachycardia, palpitations, and also blocking the peripheral conversion of T4 to T3. Immunotherapies, such as Mycophenolate mofetil and Azathioprine show promise as potential treatments are currently being investigated. This comprehensive review provides an up-to-date compact analysis of literature pertinent to the epidemiology, etiology, risk factors, genetics, pathophysiology, classifications, clinical presentation, diagnosis, and treatments of GD.

From Antibodies to Artificial Intelligence: A Comprehensive Review of Diagnostic Challenges in Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) poses diagnostic challenges due to its diverse clinical presentation and the intricacies of autoimmune thyroid diseases. This comprehensive narrative review explores the evolving landscape of diagnostic challenges in HT, aiming to provide a thorough understanding of the complexities involved in its diagnosis. The diagnostic criteria for HT involve a multifaceted approach, including clinical features, laboratory findings, and imaging studies. Serum antibodies against thyroid antigens, primarily thyroperoxidase (TPO) and thyroglobulin, play a crucial role in confirming the autoimmune nature of the disease. However, seronegative HT adds complexity by presenting without detectable antibodies. The significance of addressing diagnostic challenges lies in potential delays and misdiagnoses, emphasizing the need for accurate and timely intervention. The review explores future directions, emphasizing molecular and cellular aspects, genetic factors, and the emerging field of thyroid regeneration. Standardized diagnostic criteria are essential, considering the subjective nature of the current process. The heterogeneity of disease manifestations complicates targeted treatments, necessitating a deeper understanding of clinical presentations and underlying pathophysiology. Future research directions and challenges outlined in this review contribute to advancing our understanding and improving diagnostic precision in HT.

The association of gluten-free diet with thyroid autoimmunity in patients with celiac disease: a meta-analysis.

Background: Thyroid autoimmunity is an immune response to thyroid antigens that causes varying degrees of thyroid dysfunction. The sole effective treatment for Celiac Disease (CD) is a gluten-free diet (GFD). However, the association between GFD and thyroid autoimmunity in patients with CD has not been confirmed. Methods: A comprehensive search of several databases, involving PubMed, Embase, Web of Science, Medline, and Cochrane databases, was conducted to identify studies that primarily addressed the effects of GFD on thyroid autoimmunity in CD subjects. The meta-analysis involved studies that compared the risk of ATPO and ATG antibody positivity in CD patients with GFD, the risk of developing AITD, and the risk of developing thyroid dysfunction. Fixed-effects models or random-effects models were used to calculate the odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results: A total of 10 observational studies met the inclusion criteria and included 6423 subjects. The results indicated that GFD is positively associated with thyroid autoimmunity in the children subgroup of CD patients (OR = 1.61, 95%CI 1.06-2.43, P = 0.02). However, there was no significant difference in thyroid autoimmunity between the group adhering to GFD and the control group in the total CD population. Conclusion: The results seem to indicate that subjects with a more pronounced autoimmunity (such as to have an early onset of CD) appear to have a greater risk of thyroid autoimmunity.

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' disease (GD) and Hashimoto'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's diversity and composition. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432455.

The Potential Effect of Simvastatin on Regulatory T cells in Experimentally Induced Autoimmune Thyroiditis in Female Rats

Autoimmune thyroiditis also named Hashimoto's thyroiditis: is an inflammatory disorder of the thyroid gland. It is characterized by circulating antibodies to thyroid antigens, and enlargement of the gland with lymphocytic infiltration.
 Regulatory T cells (Tregs), a particular subset of CD4+ T cells that express CD25 at a markedly increased level. they can regulate immune response in order to preserve homeostasis and self-tolerance. T cell expansion and cytokine production are restricted by Tregs. The development of this autoimmune disease is influenced by TGF-ß1 shortage. Management of HT is usually a symptomatic therapy that concentrates on HT's symptoms rather than its underlying cause. Statins, the lipid lowering medications have pleotropic effects. they can alter immunological reactions. Twenty-four female rats were used for this experiment divided into four groups (n=6), the disease was induced in all groups except group1 (control) where rats only received phosphate buffer saline, group 2 (induction group), group 3 received Prednisolone 2mg\kg orally for 30 days and group 4 received Simvastatin (4mg\kg) orally for 30 days too. Hashimoto’s thyroiditis was induced experimentally by subcutaneous injection of porcine thyroglobulin in Freund’s adjuvant emulsion (4mg/ml). Results showed an increase in Tregs and serum TGF-ß level in rats treated with simvastatin.
 In conclusion, simvastatin improves the number of functioning Tregs and increases TGF-ß signaling to suppress the autoimmune reaction. Therefore, simvastatin can be a promising approach in the treatment of this disease.

FRI549 The See-Saw Theory - Hypothyroidism Due To Hashimoto's Thyroiditis Followed By Hyperthyroidism Due To Graves' Disease

Abstract Disclosure: P. Sharma: None. Introduction: Hashimoto's thyroiditis is an autoimmune disorder characterized by chronic inflammation of the thyroid gland that leads to hypothyroidism due to formation of autoantibodies against thyroid antigens such as thyroid peroxidase (TPO Ab). Graves' disease is caused by stimulating TSH-receptor antibodies (TRAb) that cause hypertrophy of the thyroid gland leading to hyperthyroidism. While the transformation of Graves' disease to Hashimoto's thyroiditis has been reported, flipping from Hashimoto's thyroiditis to Graves' disease is uncommon. Case Report: A 62 year old female with 20 year history of hypothyroidism secondary to Hashimoto's thyroiditis presented to establish care. She had run out of levothyroxine refills one year prior during COVID-19 pandemic restrictions. She had tachycardia, diarrhea, fatigue, tremors, hair loss, dysphagia, and weight gain. Thyroid panel testing showed hyperthyroidism with an undetectable TSH (normal range 0.45-4.5uIU/ml) and elevated free T4 (2.84, normal 0.82-1.77ng/ml). Patient denied recent infections, iodine intake or iodine contrast exposure. Repeat labs confirmed hyperthyroidism with undetectable TSH with elevated free T4 (3.17ng/ml). Antibody testing comfirmed hyperthyroidism secondary to Graves disease (TRAb 20.7, normal <1.75IU/L). Patient has been on methimazole with fluctuating response and is reviewing definitive therapy options. Discussion: We demonstrate the rare phenomenon of thyroid function transformation from long-standing inhibition to stimulation after 20 years. Hashimoto's thyroiditis is characterized by chronic inflammation due to autoantibodies against TPO, thyroglobulin and the TSH receptor with gradual gland destruction and hypothyroidism. Stimulating autoantibodies to the TSH receptor (thyroid stimulating immunoglobulin (TSIg), TRAb) in Graves' disease lead to hyperthyroidism from gland hypertrophy. The flip from underactivity to overactivity can be explained by recovery of the gland from Hashimoto's thyroiditis injury which gradually leads to an overt response to TSIg, causing a hyperfunctioning gland. An imbalance between the inhibitory and stimulating antibodies can also lead to this transformation. Age, pregnancy and immunomodulating drugs such as alemtuzumab are also thought to play a role. The recovery theory is unlikely in our patient with a 20 year history of Hashimoto's thyroiditis. We believe that she had a high inhibitory antibody titre initially and now has higher titre of stimulating antibodies later, leading to Graves' disease. Luckily, she ran out of levothyroxine otherwise the additive effect of levothyroxine and intrinsic gland activity could have led to worse symptoms. This case highlights that autoimmune hypothyroidism and hyperthyroidism are conditions in the same spectrum, rather than two distinct entities as previously thought. Presentation: Friday, June 16, 2023

FRI559 An Uncommon Association Of Two Common Etiologies Of Hyperthyroidism

Abstract Disclosure: C. Chew: None. Introduction: Subacute thyroiditis and Graves’ disease are two common etiologies of hyperthyroidism. Association of these two diseases in patient presented with recurrent hyperthyroidism has rarely been reported. Case Report: A 35 years old women, with no known medical illness, was referred to Endocrine Clinic for painful anterior neck swelling associated with palpitation for 2 weeks. The symptoms were preceded by 3 days history of sore throat and mild fever She denied other symptoms of hyperthyroidism. Her last menses was 3 weeks prior. On physical examination, she was tachycardic with heart rate of 115 beats per minute. Her blood pressure was 135/90 mmHg and she was afebrile. There was a tender and diffusely enlarged goiter. However, there were no signs of thyroid eye disease and other signs of hyperthyroidism. Examinations of her throat, lung, abdomen, cardiovascular system and neurological system were unremarkable. There was also absence of lymphadenopathy. She denied family history of thyroid disease. Results of laboratory investigations were suggestive of hyperthyroidism secondary to subacute thyroiditis: Free T4 52 pmol/L (8-16), TSH <0.01 mIU/L (0.45-4.50), TRAb 0.8 IU/L (0-1.0) and ESR 108 mm/hr (1-10). The technetium scan showed mildly enlarged gland with decreased uptake of Tc-99m tracer suggestive of thyroiditis. She was treated with Ibuprofen and Propranolol, and her symptoms improved. At 6 weeks follow up, her thyroid function normalized with Free T4 of 13 pmol/L (8-16), TSH of 1.28 mIU/L (0.45-4.50). However, she complained of weight loss and palpitation at 6 months follow up. Examination revealed a small painless diffuse goiter and she was tachycardic with heart rate of 115 beats per minute. Thyroid function test confirmed recurrence of hyperthyroidism: free T4 45.8 pmol/L (8-16) and TSH <0.01 mIU/L (0.45-4.50). Elevated TSH receptor antibody (TRAb) level at 16.8 IU/L confirmed the diagnosis of Graves’ disease. Carbimazole was then started. Discussion: Subacute thyroiditis and Graves’ disease are two common etiologies of hyperthyroidism. The incidence of association of these two diseases had been reported to be rare at 0.15% in patients with Graves’ disease and 0.76% in patients with subacute thyroiditis (1). The postulated mechanism of the association is that the release of thyroid antigens and corresponding activation of the immune system due to viral invasion of the thyroid gland in subacute thyroiditis may cause the subsequent Graves’ disease (1,2). Conclusion: Graves’ disease should be suspected in patient with persistent or recurrent hyperthyroidism after an episode of subacute thyroiditis although it is rare. Reference: 1. Nakano Y et al. Graves’ disease following subacute thyroiditis. Tohoku J. Exp. Med. 2011; 225:301-309. 2. Bartalena L et al. Graves’ disease occurring after subacute thyroiditis. Report of a case and review of the literature. Thyroid. 1996; 4:345-348. Presentation: Friday, June 16, 2023

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.

Hashimoto Thyroiditis - A Comprehensive Review

Hashimoto thyroiditis (HT) is an inflammatory disorder that often results in hypothyroidism. It has several global implications affecting different regions worldwide. Risk factors for acquiring HT include diet, inheritance, sex, epigenetics, and comorbidities. HT is a complex autoimmune illness characterized by an attack on the thyroid gland by the immune system. At the cellular level, genetic predisposition, environmental triggers, and the loss of immunological tolerance to thyroid antigens all play significant roles in the disease's genesis and progression. There are several mechanisms by which HT may develop, but the typical progression is autoimmune in origin. Many patients do not initially present with symptoms, but later develop symptoms of hypothyroidism. These symptoms include constipation, fatigue, dry skin, weight gain, cold intolerance, decreased energy, memory loss, muscle cramps, hair loss, and irregular menses. Patients with HT usually present with a firm, nontender neck goiter on a physical exam. To distinguish HT from other thyroid pathologies, patient serum should be collected to check for thyroid-specific auto-antibodies against thyroglobulin, thyroid peroxidase, thyroid stimulating hormone. Imaging studies such as ultrasonography with computer-aided techniques using gray-scale features are also diagnostic tools in differentiating between a healthy thyroid and HT. While the most common intervention of HT is synthetic hormone administration with levothyroxine sodium (L-T4), other alternatives or additional treatments include glucocorticoid use, diet alterations, selenium supplementation, vitamin D supplementation, and in more extreme cases, thyroidectomy. While research continues discovering new interventions, each treatment plan is highly variable based on underlying causes and presentations. This comprehensive review hopes to provide an up-to-date compact analysis of literature pertinent to the epidemiology, etiology, risk factors, genetics, pathophysiology, classifications, clinical presentation, diagnosis, and treatments of HT.

Hashimoto's Thyroiditis among Patients with Thyroid Disorders Visiting a Tertiary Care Centre.

Hashimoto's thyroiditis is a chronic autoimmune lymphocytic thyroiditis characterised by thyroid autoantibodies. Early detection and treatment of this condition help in reducing the morbidity and mortality associated with it. The aim of the study was to find out the prevalence of Hashimoto's thyroiditis among patients with thyroid disorders visiting a tertiary care centre. A descriptive cross-sectional study was conducted among patients visiting the outpatient department of a tertiary care centre. Data from 14 April 2017 to 13 April 2019 was collected between 30 June 2022 to 15 September 2022 from medical records. Ethical approval was obtained from the Nepal Health Research Council. Hashimoto's thyroiditis was diagnosed based on clinical presentation and positive antibodies to thyroid antigens. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Among 813 patients with thyroid disorders, 393 (48.33%) (44.89-51.77, 95% Confidence Interval) had Hashimoto's thyroiditis. The manifestation of the spectrum of Hashimoto's thyroiditis were euthyroid in 215 (54.70%), subclinical hypothyroidism in 102 (25.95%), subclinical hyperthyroidism in 23 (5.85%), overt hyperthyroidism in 9 (2.30%) and overt hypothyroidism in 4 (1.02%). The prevalence of Hashimoto's thyroiditis among patients with thyroid disorders was higher than in other studies done in similar settings. anti-thyroid peroxidase antibodies; Hashimoto's thyroiditis; thyroid disorders.

The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto's thyroiditis (HT) and hyperthyroidism (Graves-Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described.

The Effect of COVID-19 Severity, Associated Serum Autoantibodies and Time Interval after the Disease on the Outcomes of Fresh Oocyte ART Cycles in Non-Vaccinated Patients

It is assumed that SARS-CoV-2- and COVID-19-associated autoimmune processes may affect the outcomes of assisted reproductive technology (ART) cycles. This observational prospective study included 240 infertile patients: 105 patients had no history of COVID-19 (group 1) and 135 patients had experienced COVID-19 (group 2) in a mild (n = 85) or moderate (n = 50) form less than 12 months prior to oocyte retrieval. Using ELISAs, the profiles of their serum autoantibodies were determined, including antiphospholipid antibodies and antibodies to nuclear and thyroid antigens. The parameters of oogenesis and embryogenesis, as well as the pregnancy and childbirth rates, did not differ between groups 1 and 2, and also between the subgroups with different severities of COVID-19. However, when oocyte retrieval was performed less than 180 days after COVID-19, a higher proportion of poor-quality blastocysts was obtained (p = 0.006). A high risk of early miscarriage was found in the patients with moderate COVID-19. In group 2, IgG antibodies to annexin V, phosphatidylethanolamine (PE), and TSHr were detected more often than in group 1 (p = 0.035; p = 0.028; and p = 0.033, respectively), and a weak inverse correlation was revealed between anti-PE IgG and the number of oocytes and zygotes obtained. The results of the study suggest a possible adverse effect of COVID-19 and its associated autoantibodies on the outcomes of fresh oocyte ART cycles and early pregnancy, which depends on the severity of COVID-19 and the time interval after the disease.

STUDY THE EXPRESSION OF IL-22 GENE IN AUTOIMMUNE HYPOTHYROIDISM IN IRAQ

This study was aimed to assess expression of IL-22 gene in patients with newly diagnosed autoantibodies against the thyroid antigens; anti-thyroglobulin (anti-TG), and anti-thyroid peroxidase (anti-TPO) in comparison with patients previously diagnosed and treated for autoimmune hypothyroidism as well as healthy control individuals. Twenty-eight patients with positive anti-TG and/or anti-TPO were enrolled in this study along with twelve age- and gender-matched healthy controls. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess gene expression and fold change among the study groups. Results revealed anti-TG concentration ranges of 134.3 to 2998.9 IU/mL and anti-TPO concentration ranges of 41.6 to 1018.4 IU/mL in patients while control group individuals were negative for these autoantibodies. The mean fold change of IL-22 expression (2-∆∆Ct) was the highest in newly diagnosed patients compared to patients on treatment for autoimmune hypothyroidism and healthy controls indicating the potential role of IL-22 in the early stages of the disease and its contribution in immune imbalance.

Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments

Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne particle exposure.

Abstract #1395500: Silent Thyroiditis as a Complication of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine

Silent autoimmune thyroiditis, a type of chronic autoimmune thyroiditis, as an adverse effect of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is infrequently reported in the literature. We hereby describe a case of silent thyroiditis followed by Grave’s orbitopathy after vaccination against SARS-CoV2. An 84-year-old male presented to clinic with a 10-pound weight loss with no other symptoms of hyperthyroidism, no personal history of thyroid illnesses, or recent viral infections. He had normal thyroid function 3 months prior to presentation. He had received 3 doses of SARS-CoV2 Pfizer-BioNTech vaccine with the last dose 5 months prior to presentation. Thyroid exam was normal. Laboratory testing revealed thyroid stimulating hormone (TSH) level of 0.005 IU/ml (0.45-4.5 IU/ml), total T4 14.4 g/dl (4.5-12.1 g/dl), and total T3 1.22 nmol/l (0.6-1.81 nmol/l). Thyroid Ultrasound revealed a heterogeneous atrophic thyroid gland with no nodules or hypervascularity. He was started on Methimazole by primary care provider. Four months later, he was seen in the Endocrinology clinic and reported no hyperthyroidism symptoms. His TSH level at that time was 65.9 IU/ml, free T4 0.47 ng/dl (normal: 0.82-1.77 ng/dl), total T3 level 75 ng/dl (normal: 71-180 ng/dl), thyroid stimulating immunoglobulin 2.05 IU/l (0-0.55 IU/L), thyrotropin receptor antibody level 2.8 (0-1.75). Methimazole was discontinued. At 6 months after initial presentation laboratory testing showed TSH 5.010 IU/ml, free T4 1.2 ng/dl, thyroid peroxidase antibody of 148 IU/ml (normal 0-34 IU/ml), thyroglobulin antibody 131.6 IU/ml (normal 0.0-0.9 IU/ml). He was diagnosed with silent autoimmune thyroiditis. A few weeks later, the patient presented to an ophthalmologist with bilateral eye bulging and impaired vision. He was diagnosed with acute Graves’ orbitopathy and started on pulse-dose of intravenous Methylprednisolone 250 mg twice daily and urgently referred to a tertiary ophthalmology center for teprotumumab infusion. His thyroid function tests were normal at that time on no thyroid medications. The underlying mechanisms of thyroid impairment following SARS-CoV2 vaccination are not completely understood. There is a role of molecular mimicry between SARS-CoV2 antigens and thyroid antigens that may help to hasten the emergence of autoimmunity in vulnerable individuals. Our patient developed multiple thyroid-related antibodies following vaccination. Silent painless thyroiditis is a self-limiting condition, characterized by temporary thyrotoxicosis, followed by a brief period of hypothyroidism and then a complete return to normal thyroid function. A radioactive iodine uptake scan can help differentiate between the different causes of thyrotoxicosis in the acute thyrotoxic phase. Development of severe Graves orbitopathy following silent autoimmune thyroiditis after SARS COV2 vaccination has not been previously reported.

Evaluation of IL-10, MCP-1, IFN gamma, and protectin D1 levels in patients with Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is one of the most prevalent autoimmune endocrine diseases and caused by the loss of immune tolerance for the thyroid gland. Many pathophysiological mechanisms were speculated about the development of HT. In our study, we aimed to reveal the relationship between HT and IL-10, MCP-1, IFNɤ, and PD1 levels and compare them with control subjects. We collected 37 patients with HT and 25 controls referred to our outpatient clinic. The diagnosis of HT was based on the detection of circulating antibodies to thyroid antigens and decreasing echogenicity on thyroid USG in patients with appropriate clinical characteristics. Serum IL-10, MCP-1, IFNɤ, and PD1 levels were detected using an ELISA KIT (96T) method according to the manufacturer's instructions. All subjects were euthyroid (median TSH level was 1.68mU/L in HT vs 1.83mU/L in the controls, p = 0.672). Twenty-three of 37 patients with HT were taking L-thyroxin replacement. Levels of serum IL-10, IFNɤ, and PD1 in patients with HT were higher than the controls, but the differences were not statistically significant (p = 0.393, p = 0.495, and p = 0.052 respectively). The serum levels of MCP-1 in HT patients were statistically different and higher than the controls (p = 0.018). Correlation analysis displayed significant associations between IL-10, MCP-1, IFNɤ, and PD1 levels. Our study demonstrated that serum MCP-1 levels in HT patients were significantly increased; on the other hand, significant difference was not found between HT patients and the controls in terms of serum IL-10, IFNɤ, and PD1 levels.

Status of antithyroid immunity in children and adolescents with type 1 diabetes mellitus

Purpose: to determine the frequency of increased antibodies to thyroperoxidase in children and adolescents with type 1 diabetes, and to determine possible risk factors such as age, gender, age of manifestation, duration and level of glycemic control of type 1 diabetes for the development of autoimmune thyroid dysfunction. Material & Methods: anti-thyroid peroxidase antibodies (anti-TPO) level was determined in 165 children aged 8-18 years (85 girls and 80 boys) with T1DM, considering gender, duration of type 1 diabetes Mellitus (T1DM), level of sexual development at the time of T1DM manifestation and at the time of examination. Results: increased anti-TPO levels were observed in 15.8% of children with T1DM. In girls, antibodies were found twice as often (p=0.04) and were detected at a much younger age (p=0.007). The frequency of AB pressure levels before TPO significantly increased in puberty compared to childhood and puberty (p=0.03). Presumably, increased anti-TPO levels were found in children who developed T1DM before the onset of puberty (p=0.004). Conclusions: the obtained data indicate that increased levels of antithyroid antibodies are associated with female sex, puberty age and manifestation of T1DM before the onset of puberty. This confirms the need to screen all children and adolescents with type 1 diabetes for thyroid antibodies and antigens, which will reduce the risk of developing autoimmune-induced thyroid dysfunction.