What is amyloidosis?
Amyloidosis is a group of rare diseases with similar characteristics. Amyloidosis occurs when soluble proteins misshape and bind together giving rise to insoluble aggregates, called amyloid fibrils, which deposit in organs and tissues and interfere with their normal functioning. Several different proteins can form amyloid fibrils, and the type of protein determines the disease (for example, localised amyloid precursor proteins deposit in the brain in Alzheimer’s disease). The body cannot degrade these thread-like structures and without treatment amyloidosis may lead to life-threatening organ failure. There are several types of amyloidosis; AL (primary amyloidosis), AA (secondary amyloidosis) familiar ATTR amyloidosis and wild-type (senile) ATTR amyloidosis.
Some types of amyloidosis are closely related to other conditions ranging from inflammatory diseases (rheumatoid arthritis, chronic infections, Crohn’s disease) to haematological malignancies such as multiple myeloma, Waldenström macroglobulinemia and chronic lymphocytic leukemia.
AL amyloidosis is the most prevalent type of amyloidosis. However, it is still considered a rare condition, with an estimated incidence of nine cases per million person-years. It affects men slightly more often than women and the average age of diagnosed patients is 63 years.
This disease (also referred to as light chain amyloidosis) arises from abnormal plasma cells, which are a type of immune cell responsible for antibodies production. It is a disease of the bone marrow, which affects the organs outside it. In the bone marrow of AL amyloidosis patients, a plasma cell clone composed of abnormal plasma cells produces misfolded immunoglobulin light chains. These aberrant antibodies serve no purpose in the body and deposit in organs and tissues where they interfere with normal functioning. Amyloid proteins disrupt normal functioning because the body is unable to remove them, which leads to the accumulation of these proteins. Specifically, the accumulation of these proteins in vital organs such as the heart, kidneys, liver and gastrointestinal system can cause severe organ dysfunction.
Stages of AL amyloidosis
Usually, the doctor will try to determine the stage of the disease to make certain decisions about the treatment and management of your condition. There are different staging methods used across the world. The most commonly used staging of AL amyloidosis monitors heart and kidney function. They usually rely on a number of biomarkers (a biomarker is a biological feature of the body that can be measured by looking at the presence, or absence, and rate of a certain molecule) or clinical measurements. The number of clinical features that are over what is considered normal will determine which stage your illness is in. Stages go from stage I to stage III or IV (depending on the staging system) where higher stages are linked to poorer prognosis.
AL amyloidosis and myeloma
In AL amyloidosis, like in myeloma, abnormal plasma cells in the bone marrow are the source of the pathology. While, on a cellular level, the diseases are similar in AL amyloidosis, unlike myeloma, in the majority of patients, there is no large increase in the number of abnormal plasma cells. AL amyloidosis is not considered to be a cancer. In myeloma, abnormal plasma cells proliferate uncontrollably and produce one type of antibody, known as paraprotein or M-protein, which is made up of heavy and light chains but has no useful function. In AL amyloidosis patients, plasma cells proliferate less, and they produce an abnormal antibody light chain, which is deposited in tissues and organs as amyloid. They also cause/ encourage proteotoxic activity against tissue and organs, causing cell damage and even cell death, and affecting cell and organ function. Because these light chains are toxic, lowering their levels is extremely important. As a result of their shared pathophysiology, treatment of both diseases uses the same procedures and drugs, because the goal is to abolish the malignant plasma cell clones.
Furthermore, approximately 10–15% of myeloma patients will develop amyloidosis, and around 30% of patients will develop subclinical amyloid deposits, which means the disease is not clinically manifested5. In both cases, this disease is called multiple myeloma associated amyloidosis and it is treated in the same way as myeloma.
