Cellular and Genetic Basis of the Disease
Hashimoto’s Disease is characterized by many protein, gene, and cellular abnormalities. The most well-known gene disruption in Hashimoto’s Disease is the abnormalities associated in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While it is not a mutation that causes the irregularities, rather its down-regulation. A study conducted in 2003 found that those suffering from Hashimoto’s Disease exhibited mutations in the Human Leukocyte Antigen (HLA) in conjunction with the CTLA-4 down-regulation. The HLA protein has long been implicated in many autoimmune diseases such as type 1 diabetes and Celiac Disease. The connection found between these two genes is important for establishing who might suffer from Hashimoto’s or other autoimmune diseases later on.
A cell biology explanation for a possible cause of Hashimoto’s Thyroiditis involves the concept of apoptosis— cellular “suicide.” While one of the causes of thyroid cell destruction is known to be antibodies against thyroid perxodiase and thyroglobulin, another way in which the cells die is through apoptosis. Autoimmune disease are known to be particularly tough against the natural tissues of the body. Antibodies are an external factor that causes the death of healthy thyroid tissue, but apoptosis is an internal pathway that also causes the death of hyealthy thyroid tissue. Using immunohistochemistry and realtime PCR, researchers were able to identify the faulty genes and proteins that are implicated in this pathway include mutated Fas, decreased expression of Bcl-2 (a mitochondrial protein), as well as a marked increase in the expression of death agonists to death antagonists. Because mitochondrial DNA is passed down from mother to child, this apoptosis theory of disease mechanism offers a plausible explanation as to how the disease is caused by genetic factors.This finding is important as providers should be on the lookout for these gene ratios in addition to the presence of the Hashimoto’s antibodies in the blood in patients suffering from symptoms of hypothyroidism in order to rule out Hashimoto’s.
Another study implicated the SEPS1 gene as a possible genetic marker for Hashimoto’s Thyroiditis. This group studied the Han Chinese population of Hashimoto’s patients– the same population studied in 1985 in the paralysis studies discussed in the Background and History section of my theme pages. The study notes that the variations have already been noted in European population. SEPS1, also known as SELS (selenoprotein S) is a human protein which contains a selenocysteine residue at its active site. The protein is known to regulate cytokine production which is crucial for the inflammatory response in the immune system. Several single nucleotide polymorphisms (SNPs) are implicated in causing mutations to SEPS1 which can lead to uncontrolled inflammation– particularly of the thyroid tissue. This contributes to the autoimmune nature of Hashimoto’s Thyroiditis.