HLA-DR gene 

The human leukocyte antigen (HLA) complex is a collection of genes that includes the HLA-DRB1 gene. The HLA complex aids the immune system in differentiating proteins produced by the host's own cells from those produced by foreign invaders like viruses and bacteria (MedlinePlus, n.d.).

From the simple presence of thyroid autoantibodies to the development of goitrous or atrophic thyroiditis, characterised by severe thyroid failure, Hashimoto’s disease comprises a spectrum of manifestations. In terms of genetics, there have been publications linking the disease in Caucasians to HLA-DR3 and HLA-DR4 (Jacobson et al., 2008). 

TSH receptor gene 

The most frequent test results show increased thyroid-stimulating hormone (TSH) and low thyroxine (T4) levels along with enhanced antithyroid peroxidase (anti-TPO) antibodies. The present diagnosis is supported by clinical signs that are consistent with elevated TSH levels and normal to low thyroxine levels found in the laboratory  (Mincer & Jialal, 2022). 

Anti-TPO

However, it's interesting to note that there isn't much proof that anti-thyroid peroxidase (anti-TPO) antibodies play a part in the development of autoimmune thyroid disease (AITD). Anti-TPO antibodies have been demonstrated in vitro to bind to and destroy thyrocytes in addition to fixing complement. However, there hasn't yet been any connection shown in human research between the degree of sickness and the quantity of anti-TPO antibodies present in the blood. Nevertheless, it is known that a positive serum anti-TPO antibody concentration is associated with the disease's active stage. Other hypotheses suggested that immune complexes containing thyroid-specific antibodies were to blame for the death of the thyroid (Mincer & Jialal, 2022). 

In autoimmune conditions, the absence of microbial agents due to high levels of hygiene has been strongly linked to the development of autoimmune diseases. Certain lifestyle factors, such as moderate smoking and alcohol consumption, have been found to have a protective effect against Hashimoto's disease. Prolonged exposure to stressful situations can also increase the risk of developing Hashimoto's disease. Moreover, dietary factors play a role, with meat consumption being associated with a higher risk of thyroid autoimmunity, while a diet rich in plant-based, fat-free foods containing fiber and antioxidants reduces the risk of developing Hashimoto's disease (Jin, B. et al, 2022). 

Interestingly, research indicates that women born during summer months have a slightly higher incidence of Hashimoto's disease compared to the general female population. Seasonal variations, such as exposure to viral and bacterial infections or vitamin D levels, could potentially explain the observed associations. The relationship between infectious agents and the development of autoimmune thyroid disease (AIT) has been extensively studied, leading to various theories regarding the disease's pathogenesis. These theories include concepts like molecular mimicry, where infections trigger an immune response against self-antigens, and the release of sequestered antigens due to local infection and inflammation. Viruses such as Coxsackie-B virus and Parvovirus B19 have been implicated as potential triggers for autoimmune thyroid disease. Additionally, the occurrence of other autoimmune diseases like insulin-dependent diabetes mellitus (IDDM) and multiple sclerosis (MS) has also demonstrated seasonal variation, further supporting the notion that environmental factors influenced by seasonal changes may impact the risk of developing autoimmune thyroid disease.

(Thvilum et al, 2017) 

In Hashimoto's disease, the thyroid gland is incorrectly perceived by the immune system as a threat, prompting an immunological reaction against it. It is believed that a combination of humoral and cell-mediated immunity is responsible for this immunological dysregulation.

Humoral immunity

Humoral immunity is an adaptive immune response that is exhibited by the B cells' production of antibodies (Pal & Chakravarty, 2019). The capacity of Hashimoto's disease patients' thyroid tissue-derived B cells to spontaneously generate antithyroid antibodies in vitro demonstrates that these cells are activated.

As a result, the thyroid may be a key location for thyroid antibody release as suggested by the decrease in serum thyroid antibody concentrations that happens following surgery and when antithyroid medications are given to patients with this illness (Pyzik et al., 2015). 

2 types of autoantibodies

• Thyroid peroxidase antibodies (TPOAb) attacks thyroid peroxidase (an enzyme involved in thyroid hormone synthesis)

• Thyroglobulin antobodies (TgAb) attacks thyroglobulin  (a protein involved in thyroid hormone production)

Cell-mediated immunity

Effector T-cell function in humoral and cellular immune responses to representative pathogens. Cell-mediated immune reactions include the cytotoxic T cell killing of infected cells or the eradication of intracellular pathogens by macrophages. Primary immunological responses are made up of naive T cells that have been activated in response to antigens, followed by their proliferation and differentiation (Janeway et al., 2001).

In the pathogenesis of Hashimoto's disease, excessively stimulated CD4+ T cells play a crucial role. T helper type 2 (Th2) cells stimulate B cells and plasma cells, which produce antibodies against thyroid antigens, leading to thyroid inflammation. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) are both produced by T helper type 1 (Th1) and Th2 cells, respectively. IFN-gamma and IL-4 production-related gene variants are frequently found in patients with severe Hashimoto's disease (Pyzik et al., 2015).