Ask the Nurse: Paraproteins and free light chains

In this month’s blog, we answer some of the questions you ask us about paraproteins and free light chains.

Most patients will hear the terms paraprotein and free light chain for the first time at diagnosis. Their presence in the blood or urine is one of the most common features of myeloma. As a result, paraprotein and free light chain tests play a key role in diagnosing and monitoring myeloma. We often get questions from patients and carers about these proteins, what they are, where they come from and why they are measured.

In this month’s blog, we answer some of the questions you ask us about paraproteins and free light chains.

What are paraproteins?

Myeloma arises from plasma cells, a type of cell found in our bone marrow. Plasma cells form part of our immune system producing proteins called antibodies (immunoglobulins) to help our body fight infection.

In myeloma, these plasma cells become abnormal, multiply uncontrollably and produce a large amount of a single type of antibody (known as paraprotein or M-protein) which has no useful function. It is often through the measurement of paraprotein in the blood or urine that myeloma is diagnosed and monitored.

What are free light chains?

Antibodies are made up of two parts, heavy chains and light chains. When making antibodies, plasma cells normally make more light chains than required. These lights chains enter the blood as free light chains.

Therefore, as myeloma cells produce the paraprotein they also produce excess amounts of one type of light chain.

Do all myeloma patients have paraproteins?

Although they are commonly used to diagnose and monitor myeloma not all myeloma patients have paraproteins.

In fact, in around 20% of patients, the abnormal plasma cells produce only the light chain part of the paraprotein. This is called ‘light chain’ myeloma. In this instance, patients are monitored using light chain levels.

More rarely, in less than 1% of patients, the abnormal plasma cells produce no detectable paraprotein or light chains; known as ‘non-secretory myeloma’. Consequently, patients with non-secretory myeloma are generally monitored using bone marrow biopsies and imaging.

Can patients have more than one paraprotein?

Typically, the abnormal plasma cells only produce one type of paraprotein. However, in very rare cases, two paraproteins can be detected. This is sometimes called ‘biclonal gammopathy’ or ‘double myeloma’ and can be present at diagnosis or develop later. For patients with biclonal gammopathy, monitoring of their myeloma involves measuring both paraproteins.

What is a high level of paraprotein?

People without myeloma and related conditions don’t have paraproteins. Any level of paraprotein that is found in the blood or urine is therefore considered to be abnormal. The type and level of paraprotein that is observed can vary between individuals, such that a high level of paraproteins in one patient could be low for another. The level of paraproteins can also fluctuate between tests. Therefore, the haematologist will not look at the quantity of paraprotein that they observe at a single time point, but how the level of paraprotein varies over time. They will also consider any changes in symptoms or complications such as kidney function and peripheral neuropathy which can be caused by high levels of paraprotein.

Whilst on treatment, the haematologist will look for a decrease or a stabilization in paraprotein levels. Some patients will still have a stable low level of paraprotein after treatment: this is known as a plateau. If you are in a plateau you will have similar testing to patients in remission, but they may be more frequent.

What is a free light chain ratio and why is it measured?

The light chains in antibodies come in two types – kappa (κ) and lambda (λ).

In people without myeloma, light chains are present in the blood, but the balance between kappa and lambda types (called the kappa to lambda ratio or free light chain ratio) will be fairly even.

In myeloma, the myeloma cells produce either kappa or lambda light chains only, so the level of that type will be higher, and the kappa to lambda ratio will change.

An abnormal ratio can indicate active myeloma and is considered to be as important as the kappa and lambda levels for diagnosing and monitoring myeloma.

For more information about tests and investigations, you can read the Myeloma UK Infoguide “Tests and investigations in myeloma”, which is available to download from the Myeloma UK website.

If you have any questions about test results you can also get in touch with us through the Infoline (0800 980 3332 (UK) or 1800 937 773 (Ireland)) or the Ask the Nurse email service.

Best Wishes

The Myeloma UK Information Specialist Team

Close-up photograph of a hand holding a mobile phone.

Stay in touch

We’d love to stay in touch. Join our mailing list to receive updates from Myeloma UK including our monthly newsletter and updates about our services, research, campaigns and other ways you can get involved.