Overview
Monoclonal gammopathy of undetermined significance (MGUS) is a condition caused by altered plasma cells. A plasma cell is a type of white blood cell that usually makes disease-fighting antibodies.
In MGUS, plasma cells in bone marrow make monoclonal proteins that circulate in the blood. These proteins also may be called M proteins, myeloma proteins or paraproteins. The amount of monoclonal protein is low in MGUS, and the plasma cell condition doesn't cause myeloma-related organ damage. Most people with MGUS don't get multiple myeloma.
MGUS is not cancer, but having MGUS raises the risk of getting cancer of the plasma cells and related conditions.
MGUS doesn't require treatment. With regular checkups and blood tests, your healthcare team looks for changes in M protein levels and signs of cancer or other diseases. If your healthcare team suspects that MGUS is getting worse, also called progressing, they may test whether the number of altered plasma cells has increased.
Types
Monoclonal gammopathy of undetermined significance (MGUS) has three main types. They differ in the type of monoclonal protein involved and in the conditions to which they are most likely to progress.
- Non-IgM MGUS. This is the most common type of MGUS. The M protein usually is immunoglobulin (Ig) G or IgA. If non-IgM MGUS progresses, it most often becomes multiple myeloma or, less commonly, amyloid light-chain (AL) amyloidosis.
- IgM MGUS. The M protein is IgM. If IgM MGUS progresses, it is more likely to become Waldenstrom macroglobulinemia, a type of lymphoma, than become multiple myeloma.
- Light-chain MGUS. Instead of making a whole antibody, the altered plasma cells make only part of an antibody, called a light chain. The light chain may be kappa or lambda. A blood test called a serum free light chain test helps find this type. If light-chain MGUS progresses, it can develop into light-chain multiple myeloma or amyloid light chain (AL) amyloidosis.
What do terms such as IgG kappa mean?
The name of an M protein may describe both its antibody type and its light chain:
- IgG, IgA and IgM describe the type of antibody.
- Kappa and lambda are the two types of light chains.
- IgG kappa, for example, means the M protein is an IgG antibody with a kappa light chain.
These terms describe the type of monoclonal protein found. They do not, by themselves, mean that you have cancer.
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Symptoms
People with MGUS usually don't have symptoms. Most often, the condition is found with blood tests done for regular checkups or for diagnosing another condition.
Causes
Experts don't know exactly what causes MGUS. It begins when a group of plasma cells gets genetic changes and starts making copies of the same monoclonal protein. Researchers know that these changes help establish the altered group of plasma cells, but they don't know what triggers the changes in most people.
Factors such as age, family history, obesity and some environmental exposures are linked to MGUS. But having one or more risk factors doesn't mean that they caused MGUS. These factors are discussed in more detail below.
Risk factors
Factors that increase your risk of getting MGUS include:
- Age. MGUS becomes more common with age. About 3% of people older than 50 have MGUS compared with about 5% of people older than 70 and 9% of people older than 85.
- Race. Black people and people of African descent have a higher risk of MGUS than do other people. Some studies suggest that MGUS is less common in Asian American people than in non-Hispanic white people.
- Sex at birth. MGUS is more common in men.
- Family history. A family history of MGUS raises your risk.
- Weakened immune system. Having a weakened immune system is linked to a higher risk of MGUS.
- Chemical exposure. Exposure to toxic chemicals in the workplace or environment — such as pesticides, asbestos and fertilizers — may raise the risk of MGUS.
- Things you can change. Obesity and cigarette smoking have been linked to MGUS.
Complications
Each year, about 1% of people with MGUS get cancer of the plasma cells or related conditions. The risk varies from person to person. These conditions include the following:
- Multiple myeloma. This is cancer of the plasma cells in the bone marrow. It results in poor blood cell production, weakened bones and bone pain.
- Lymphomas. These are cancers that begin in the lymphatic system, which is part of the immune system. They develop when lymphocytes, a type of white blood cell, grow and multiply out of control. Some types of MGUS can become certain lymphomas.
- Waldenstrom macroglobulinemia. This is a type of lymphoma that can develop from IgM MGUS. The altered cells make an IgM M protein. This may cause thickened blood, bleeding, frequent infections, and a liver and spleen that are larger than usual.
- AL amyloidosis. This happens when light chains from M proteins build up as amyloid in tissues and organs. These amyloid proteins often build up in the heart, kidneys and nerves.
Monoclonal gammopathies of clinical significance
M proteins may cause disease in tissues and change how organs function. If this type of M protein-related condition develops, it's called monoclonal gammopathy of clinical significance. These conditions may affect the:
- Kidneys.
- Nervous system.
- Eyes.
- Skin.
Other complications
Other complications include:
- Osteoporosis and bone fractures. People with MGUS may have a higher risk of osteoporosis and bone fractures. Osteoporosis causes bones to become weaker and more likely to break.
- Risk of infections. MGUS raises the risk of viral and bacterial infections, especially infections of the nose, throat and lungs.
- Venous thromboembolism. MGUS also raises the risk of blood clots in veins. Clots can block the flow of blood. This condition is called venous thromboembolism.
Sept. 16, 2026