By Dr Sophie Georgin-Lavialle - Tenon Hospital PARIS - FRANCE
The formation of amyloidosis
Throughout our lives, the cells of our bodies are renewed thanks to their DNA which is like a computer program and which codes to make molecules called proteins, indispensable to ensure that our bodies function well. Indeed, proteins provide the structure and function of nearly all life’s biological processes.
Once the proteins have been produced by our cells, they naturally adopt a specific shape. This shape enables them to fulfil their function inside the human body. When they are folded correctly our body functions well and we are in good health.
But if they fold badly (this is what we call misfolding), it can harm the functioning of our body and cause health problems with time. In general, our body is able to identify misfolded (abnormal) proteins and eliminate them as they occur.
In certain diseases, our body produces too many abnormal (misfolded) proteins for it to deal with. In this way our body is overwhelmed and unable to destroy them. Consequently, this surplus of abnormal proteins is stored in the body.
When a protein misfolds, we speak of an amyloid protein. When these amyloid proteins accumulate, they stick together forming lines of rigid fibrils, like plaited plastic threads.
These rigid fibrils accumulate in the organs forming amyloid plaques which prevent them from functioning properly.
The fibrils are very tough and hard to break. When organs are infiltrated by these plaques, we speak of amyloidosis. Thus, amyloidosis is a disease linked to an abnormal folding of proteins in the body. Amyloid deposits in organs of the body can be compared to deposits of limescale at the bottom of an electric kettle. When these organs are coated with amyloid fibrils, they function less well and different clinical signs may appear.
The great diversity of amyloidosis
There are several types of amyloidosis. So far, more than twenty-five proteins have been identified as being able to cause amyloidosis.
These proteins are known as “precursors” of amyloidosis.
A simple classification has been set up. It consists in using the letter “A” for amyloidosis, followed by the abbreviation of the precursor protein. The great diversity of amyloidosis A TTR The different types of amyloidosis can be classified according to the name of the precursor protein. The letter “A” + the abbreviation of the protein name, like TransThyretin in our example.
Nomenclature of the main typess of amyloidosis
|ATTR||TTR for Transthyretin||Transthyretin amyloidosis|
|Mutated Transthyretin||Familial or hereditary amyloidosis|
Non-mutated Transthyretin (wild)
|AL||L for “Light Chain”||AL Amyloidosis|
|AA||A for Serum Amyloid A||AA Amyloidosis|
The symptoms and affected organs depend on the type of amyloidosis. Similarly, the treatment offered to patients varies greatly according to the identified amyloidosis.
Care is also different for each patient who can be more or less seriously affected in different parts of the body for the same disease.
The symptoms encountered in amyloidosis are often vague and not very clearly defined at the outset. Due to the variety of initial symptoms and the rare nature of the disease, which is not well-known to doctors, diagnosis is often delayed.
A study carried out by the association of American patients has shown that the time between the first symptoms and the diagnosis was about one year and that patients had seen an average of five doctors before being diagnosed.
However, it is important that the diagnosis be made as quickly as possible to prevent the gradual impairment of the organs, particularly cardiac impairment.
The only way to make a definite diagnosis of amyloidosis is to carry out a biopsy.
Biopsy consists in taking a small fragment of tissue from an affected organ and then examining it under the microscope. It is a minor operation under local anaesthetic, which can be performed in the doctor’s surgery.
When the biopsy of a tissue is carried out, the sample is taken to an anatomical pathology laboratory where it is subjected to a specific stainin using a substance known as Congo Red.
Congo Red dyes the amyloid deposits which appear as an amorphous substance in the tissues.
Once amyloidosis has been detected in an organ, it is necessary to find out what kind of amyloidosis it is by using further techniques.