Amyloidosis - a fatal overproduction of antibodies

A type of white blood cell called plasma cells produced in the bone marrow, are responsible for producing the antibodies that detect foreign invaders including viruses. However, researchers have discovered a gene mutation in the cells that when present can result in the cell going into abnormal cell proliferation, with associated antibody production. Antibodies are comprised of two long and two short protein chains. The short chains in the antibody are called the light chains. Over-production of light chains leads to deposition of the excess material in various cell types and organs, and this causes a potentially fatal disease called amyloidosis.

A research team from the Technical University of Munich (TUM) and Heidelberg University has now identified the mutation behind the disease in a patient.

A recent paper titled, 'Fatal amyloid formation in a patient’s antibody light chain is caused by a single point mutation', demonstrates that they have identified the mutation behind this fatal disease.

Antibodies are normally vital for the survival of human beings. They typically consist of two longer and thus heavier amino acid chains and two lighter ones. In rare cases, the plasma cells multiply excessively, flooding the body with light antibody chains.

In people suffering from light chain amyloidosis (AL amyloidosis), these light chains are deposited as extremely fine fibers, so-called amyloid fibrils, in tissue or in organs. The disease is often recognized only after the deposits already compromise the function of organs. In many cases AL amyloidosis is fatal.

"To date, little was known about the exact cause of this amyloidosis," says Johannes Buchner, professor of biotechnology at the Technical University of Munich. “Depending on the organ affected, the symptoms vary considerably. Furthermore, each patient produces different types of antibodies. The disease is thus difficult to diagnose at an early stage.”

A mutation triggers the deadly disease

Using various analytical and database-supported methods, the team of scientists succeeded in identifying eleven mutations caused by the disease in the antibodies of a patient with advanced AL amyloidosis.

Further investigations showed that exactly one mutation was responsible for the destabilization and formation of the disease-causing amyloid fibrils. This mutation causes the unstable light chain to lose its structure after breaking into fragments, which then form the deadly amyloid fibrils.

"Our study shows that mutations that lead to unstable light chains are an important factor in the occurrence of amyloidosis," says Pamina Kazman, who carried out the majority of the measurements. "In the long term, we hope that these and other studies will lead to new, earlier diagnostic methods and possibly even new treatment options."

The protein structures were determined at the synchrotron radiation sources of the Paul Scherrer Institute in Villigen (Switzerland) and the European synchrotron radiation source in Grenoble (France).

An organic compound that is the basic building block of all proteins. Full medical glossary
A compound similar to starch, which can build up abnormally in the tissues in a condition called amyloidosis. Full medical glossary
A variety of conditions in which a protein called amyloid builds up in organs or tissues. Full medical glossary
Special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. Full medical glossary
One of a group of special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. Full medical glossary
A fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. Full medical glossary
Tissue within the bones where blood cells are formed. Full medical glossary
The basic unit of all living organisms. Full medical glossary
One of the three main food constituents (with carbohydrate and protein), and the main form in which energy is stored in the body. Full medical glossary
The basic unit of genetic material carried on chromosomes. Full medical glossary
A change in the genetic material (DNA) of a cell, or the change this this causes in a characteristic of the individual, which is not caused by normal genetic processes. Full medical glossary
A craving to eat non-food substances such as earth or coal. Full medical glossary
Fluid in which the blood cells are suspended. Full medical glossary
Compounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. Full medical glossary
Energy in the form of waves or particles, including radio waves, X-rays and gamma rays. Full medical glossary
A group of cells with a similar structure and a specialised function. Full medical glossary
A microbe that is only able to multiply within living cells. Full medical glossary
Microbes that are only able to multiply within living cells. Full medical glossary