Hashimoto's Disease

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Hashimoto’s Disease

Hashimoto’s disease, also known as Hashimoto's thyroiditis, is a typification of autoimmune thyroiditis. Hashimoto’s disease is characterized by painless enlargement of the thyroid, which, in histopathological analysis, presents diffuse lymphocytic infiltrations, fibrosis, and atrophic changes. It is a diffuse process, a combination of epithelial cell damage, lymphocyte infiltrations, and fibrosis, finally leading to gradual destruction of thyroid gland. Investigation showed that middle-aged women are more sensitive than men and children.

Signs and Symptoms of Hashimoto’s Disease

People at the early stage of Hashimoto’s disease usually do not feel sick at all, over time their thyroid may enlarge, eventually develops hypothyroidism accompanied by the following signs and symptoms. After many years the thyroid typically shrinks in size, and thyroid lymphoma is a potential complication.

  1. Fatigue and sluggishness
  2. Increased sensitivity to cold
  3. Constipation
  4. Pale, dry skin
  5. A puffy face
  6. Brittle nails
  7. Hair loss
  8. Enlargement of the tongue
  9. Unexplained weight gain
  10. Muscle aches, tenderness, and stiffness
  11. Joint pain and stiffness
  12. Muscle weakness
  13. Excessive or prolonged menstrual bleeding (menorrhagia)
  14. Depression
  15. Memory lapses

Fig. 1 Hashimoto’s disease/ thyroiditis is one of thyroid diseases. (Macvanin et al., 2023)

Fig. 1 Hashimoto’s disease/ thyroiditis is one of thyroid diseases.1

Factors in the Pathogenesis of Hashimoto’s Disease

  1. Antithyroid Antibodies

The antibodies against thyroperoxidase (anti-TPO), antithyroglobulin (anti-Tg) and more rarely TSH-stimulation blocking antibody (TSBAb), are positively correlated with an increased inflammatory reaction in the thyroid and with the development of Hashimoto’s disease. Antithyroid antibodies have an ability to fix complement and thus promote complement-dependent antibody-mediated cytotoxicity leading to more damage to thyroid tissue.

  1. T and B Lymphocytes

In patients with Hashimoto’s disease, B cells from thyroid tissue are activated to secrete antithyroid antibodies, the major pathogenic factors. It is acknowledged that excessively stimulated T cells CD4+ play the main role in the pathogenesis of Hashimoto’s disease. Moreover, T helper cells (Th1, Th2, and Th17) are also involved in the development of Hashimoto’s disease. Th2 cells lead to excessive stimulation and production of B cells, resulting in antithyroid antibodies accumulation. While Th1 cells activate cytotoxic lymphocytes and macrophages, leading to direct effects on thyroid tissue by destroying thyroid follicular cells.

  1. Complement Components

As an important parameter of Hashimoto’s disease, thyroperoxidase consists of a large N-terminal myeloperoxidase-like module followed by a complement control protein (CCP)-like module and an epidermal growth factor-like module. C4 may bind to thyroperoxidase and activate the complement pathway in autoimmune thyroiditis. Autoantibodies against complement C1q (anti-C1q) are correlated with parameters of thyroid function and anti-TPO, anti-Tg and TSBAb. The researches of C3 in the pathogenesis of Hashimoto’s disease shows that the severity and duration of the thyroid dysfunction correlate with the degree of complement activation.

Pathogenesis of Hashimoto's disease.

Fig.2 Pathogenesis of Hashimoto's disease. (Fröhlich, 2017)

Creative Biolabs has established advanced Complement Therapeutics platform including antibody engineering platform, protease inhibitor platform, and drug discovery platform, and is equipped to offer a full range of biotherapeutics development services regarding drug discovery and validation for Hashimoto’s disease. Please contact us for detailed information.

References
1. Macvanin, Mirjana T., et al. "New biomarkers: prospect for diagnosis and monitoring of thyroid disease." Frontiers in Endocrinology 14 (2023).
Fröhlich, Eleonore, and Richard Wahl. "Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases." Frontiers in immunology 8 (2017): 521.

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Questions & Answer

A: Complement-targeted therapies aim to address the underlying autoimmune process in Hashimoto's disease, whereas traditional treatments like hormone replacement therapy focus on managing the symptoms caused by thyroid dysfunction. Complement therapeutics have the potential to modify the disease course, but more research is needed to determine their comparative effectiveness and safety.

A: Yes, there is ongoing research into complement inhibitors as potential therapeutics. Compounds targeting complement proteins like C3 and C5 are being explored to dampen the inflammatory response in Hashimoto's.

A: Developing drugs targeting complement factor B involves a multi-faceted approach. Researchers can explore small molecules, monoclonal antibodies, or other biologics that specifically inhibit complement factor B's enzymatic activity. Computer-aided drug design, high-throughput screening, and structural biology techniques can aid in identifying potential drug candidates. Preclinical studies involving animal models and in vitro assays are essential to assess efficacy and safety before advancing to clinical trials.

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