M protein is an abnormal antibody (immune protein) made by cancerous plasma cells. It is a molecule that isn’t normally made by the body. The “M” technically stands for “monoclonal,” but M protein is often referred to as “myeloma protein.” High amounts of M protein in a person’s blood or urine may be a sign they have multiple myeloma — but the presence of M proteins could also indicate other types of plasma cell tumors.

What Is M Protein?

M protein is made by abnormal plasma cells. In order to understand M protein, it helps to know more about how plasma cells work.

Plasma cells are part of the immune system. They develop from B cells (a type of white blood cell). A plasma cell’s job is to make proteins that fight off germs like bacteria and viruses. These proteins are called antibodies or immunoglobulins. Plasma cells make antibodies using genes that tell the cell how to make the antibody protein. As plasma cells develop, each cell’s antibody-producing genes become rearranged in a unique way. This means that each plasma cell is genetically different and makes a slightly different antibody. Having a wide variety of antibodies helps plasma cells to fight off lots of different types of infections.

Abnormal or cancerous plasma cells don’t develop in the usual way. They are produced when one single plasma cell becomes damaged and produces many clones of itself. These cloned cells all have the same gene rearrangements and make monoclonal immunoglobulins (antibodies that are exactly the same). This type of protein goes by many names, including M protein, myeloma protein, monoclonal protein, M spike, or paraprotein.

M proteins don’t work properly. They can’t fight germs as well as other antibodies. They can also damage the kidneys and other organs.

What Do High Levels of M Protein Mean?

High M protein levels are a sign that a person has abnormal plasma cells. M protein can be a sign of several different types of diseases. Tests that measure M protein may be used to determine:

• A condition
• The stage of a disease
• Whether the condition is getting worse
• How well treatments are working

Diagnosing Multiple Myeloma

Having M protein in your system may be a sign of multiple myeloma. Most people with myeloma have M protein in their blood or urine. If you have M protein, your health care provider will likely recommend other tests before making a diagnosis of multiple myeloma. These tests may include:

• Imaging tests
• Genetic tests
• Bone marrow biopsies (when doctors take a sample of the soft tissue from inside your bones)
• Other blood tests

Diagnosing Other Diseases Using M Protein

Finding M protein in the blood or urine does not necessarily mean a person has multiple myeloma. There are several other plasma cell disorders that may also result in high levels of M protein.

Lower levels of M protein may mean a person has a disorder called monoclonal gammopathy of undetermined significance (MGUS). This condition occurs when there are small numbers of abnormal plasma cells in the bone marrow. People with MGUS don’t have any signs or symptoms of multiple myeloma, but they have an increased risk of developing it. Researchers estimate that about 20 percent of people with MGUS will eventually develop multiple myeloma. Each year, there is a 1 percent chance that a person’s MGUS will turn into myeloma.

MGUS can also sometimes lead to other diseases such as leukemia, Waldenström macroglobulinemia, or amyloidosis. MGUS can be considered the first step toward myeloma, followed by smoldering multiple myeloma (SMM).

People with SMM — also called asymptomatic myeloma — have increased levels of plasma cells but do not have any other myeloma symptoms. But eventually, smoldering myeloma usually turns into multiple myeloma. The risk of developing multiple myeloma in people with SMM is:

• 10 percent per year for the first five years
• 3 percent for the next five years,
• 1.5 percent each year after that

In recent years, a consensus has developed that treating SMM is beneficial, but it can be delayed in some circumstances. Early treatment is recommended for cases of “high-risk” SMM, which are defined by specific criteria, including when you have a high level of a serum M protein in your blood.

If an M protein test reveals that you have a condition like SMM or MGUS, you can take steps to protect your health. Knowing you’re at risk for developing a condition like myeloma can help you catch it early. People with SMM or MGUS should have regular follow-up visits and tests. If the condition transforms into myeloma, it can be found and treated right away, which may lead to a better outcome.

M Protein in Monitoring Diseases and Treatments

After a condition is diagnosed, doctors may rely on M protein levels to provide other information. M protein levels can help in determining myeloma stages (how advanced the condition is). Health care providers commonly use two systems to classify myeloma into stages. One of them, the Durie-Salmon Staging System, partly bases stages on how high M protein levels are. The newer classification system, known as the Revised International Staging System (R-ISS) for multiple myeloma, does not include M protein in its criteria.

Health care providers may also continue measuring M protein levels after diagnosis so they can see when a disease is getting worse. For example, M protein levels may indicate when SMM or MGUS has transformed into myeloma. M protein levels can also help show whether myeloma is becoming more advanced, which may indicate that a person’s treatment plan should change.

M protein levels can also show whether myeloma treatments are working. If a treatment is successful, M protein levels will decrease and eventually reach zero.

How Is M Protein Measured?

Some tests measure M protein levels while others analyze the M protein type. It’s important to know which type of M protein your plasma cells make.

Antibodies, including M proteins, are made up of two different types of proteins. Each antibody contains two heavy-chain proteins and two light-chain proteins. There are five different types of heavy chains:

• Immunoglobulin (Ig) G (IgG)
• IgA
• IgM
• IgD
• IgE

Determining which type of M protein (according to its heavy-chain and light-chain proteins) is in your blood or urine can help your health care team diagnose specific conditions. For example, about 50 percent of people with multiple myeloma have M protein made up of IgG proteins. The second largest group has IgA. Most of the time, IgM proteins are a sign of Waldenström macroglobulinemia.

Blood Tests

Some tests measure M proteins from blood samples. One such test is serum protein electrophoresis (SPEP). This test separates the proteins within a sample based on their electrical charges. SPEP shows changes in the levels of both M protein and other normal proteins. It reports the overall levels of M protein, but it doesn’t show what type of M protein a person has.

Immunofixation electrophoresis (IFE) tests may be performed along with an SPEP test. IFE tests show what type of M protein a person has, but it doesn’t show the overall levels.

Blood tests may also include a quantitative immunoglobulins test. This test determines the type of M protein found in the blood. A quantitative immunoglobulins test can measure the levels of IgG, IgA, and IgM. The test can help measure levels of both M protein and other normal immunoglobulins over time.

Another M protein blood test is a serum free light chain (SFLC) assay. Although antibodies are made from both heavy- and light-chain proteins, plasma cells usually make more light-chain proteins. The extra light chains that aren’t used to make antibodies are released into the blood. The SFLC assay measures these blood proteins.

Urine Tests

The urine protein electrophoresis (UPEP) test works the same way as the SPEP but uses a urine sample. Urine tests often also include tests for just the light chain part of the M protein. This is because the body eliminates extra light-chain proteins that are not attached to heavy proteins through the urine. When light-chain proteins show up in the urine, they are called Bence-Jones proteins.

UPEP involves a 24-hour urine sample. To provide this sample, you will collect all of your urine in a 24-hour period. Your health care provider can give you further instructions if you need to take a UPEP or other urine test.

What Is the M Protein Level in Multiple Myeloma?

M protein levels can be used to tell the difference between MGUS, SMM, and multiple myeloma. According to the International Myeloma Working Group (IMWG), MGUS is characterized by a blood M protein level of less than 30 grams per liter. People with SMM have blood M protein levels of 30 grams per liter or higher or a urine M protein level of 500 milligrams per 24 hours.

According to the Durie-Salmon Staging System, the criteria for stage 1 multiple myeloma include a urine light chain M protein level of less than 4,000 milligrams per 24 hours. Blood levels of M protein depend on the type of antibody. Levels of IgG M protein lower than 50 grams per liter and levels of IgA lower than 30 grams per liter are also criteria for stage 1.

People with stage 3 multiple myeloma may have urine light chain M protein levels of more than 12,000 milligrams per 24 hours. Blood IgG M protein levels greater than 70 grams per liter and IgA M protein levels greater than 50 grams per liter are also criteria for stage 3 multiple myeloma.

Your health care provider can give you more information about what your M protein levels mean for you and your treatment.

Talk With Others Who Understand

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