Transthyretin - Histology

What is Transthyretin?

Transthyretin (TTR) is a protein primarily produced in the liver and the choroid plexus of the brain. It is a homotetrameric protein, meaning it consists of four identical subunits. TTR functions primarily as a transport protein, binding and transporting thyroxine (T4) and retinol-binding protein bound to retinol (vitamin A) in the blood and cerebrospinal fluid.

What is the role of Transthyretin in Histology?

In histology, TTR is significant because it can be involved in the formation of extracellular deposits known as amyloid. These deposits are associated with several diseases, most notably transthyretin amyloidosis (ATTR). Histological examination of tissues affected by ATTR can reveal amyloid deposits, which are typically stained with special dyes like Congo red to confirm their presence.

How is Transthyretin Visualized in Tissue Sections?

Histological visualization of TTR in tissue sections is often achieved through immunohistochemistry (IHC). IHC uses specific antibodies that bind to TTR, which can then be visualized using various detection systems. This technique allows researchers and pathologists to localize TTR within tissues and assess the extent of amyloid deposition.

What are the Clinical Implications of Transthyretin in Histology?

The accumulation of TTR as amyloid deposits in tissues can lead to organ dysfunction. In the heart, this can cause restrictive cardiomyopathy, while in the nervous system, it can lead to peripheral neuropathy. Histological examination of biopsies from affected organs can provide crucial diagnostic information, confirming the presence of TTR amyloid and guiding treatment decisions.

How is Transthyretin Amyloidosis Diagnosed?

Diagnosis of TTR amyloidosis often involves a combination of clinical assessment, imaging studies, and histological examination of tissue biopsies. Congo red staining of tissue sections, followed by examination under polarized light, can reveal apple-green birefringence indicative of amyloid. Immunohistochemistry can further confirm the presence of TTR within the amyloid deposits. Genetic testing may also be performed to identify mutations in the TTR gene that predispose individuals to hereditary forms of the disease.

What are the Treatment Options for Transthyretin Amyloidosis?

Treatment options for TTR amyloidosis include medications that stabilize the TTR protein, preventing it from misfolding and forming amyloid deposits. Examples include tafamidis and diflunisal. In some cases, liver transplantation may be considered, as the liver is the primary source of TTR production. Continuous advancements in understanding the molecular basis of TTR amyloidosis are paving the way for new therapeutic strategies.

Conclusion

Transthyretin plays a critical role in the transport of thyroid hormones and retinol, but its propensity to form amyloid deposits under certain conditions makes it a significant focus in histology. Understanding the histological presentation of TTR and its related pathologies is essential for accurate diagnosis and effective treatment of diseases such as transthyretin amyloidosis.