What Is M Protein (Myeloma Protein)?

To check if you have a cancer called multiple myeloma, your doctor may ask you to get a test for M protein. If the substance shows up in your blood or urine, it's a sign you might have that disease or another condition.

M proteins go by a lot of different names. You may hear your doctor call them "monoclonal " proteins. They're also called monoclonal immunoglobulin, mylenoma, M spike, or paraprotein.

Whatever their name, they're made in your bone marrow, the spongy tissue in the middle of many bones. That's where blood cells form. One kind of white blood cell, called a plasma cell, plays a big role in your immune system -- your body's defense against germs.

To fend off sickness, plasma cells release proteins called antibodies. Thy find and kill viruses, bacteria, and other substances. But sometimes, plasma cells make abnormal proteins, which are the ones called M proteins. These are antibodies or incomplete antibodies that are all exactly the same, which is called monoclonal. These M proteins don't have any power to fight infection.

Conditions Linked to M Proteins

A variety of conditions are related to M proteins:

MGUS (monoclonal gammopathy of undetermined significance). If you have this condition, you have both healthy plasma cells and abnormal ones. The abnormal plasma cells make M proteins that show up in your blood. Most of the time, MGUS doesn't cause any problems or symptoms. But for some people, MGUS turns into a harmful condition, such as multiple myeloma or lymphoma.

Smoldering multiple myeloma. This is the stage between MGUS and myeloma. There are more abnormal plasma cells and M proteins in the blood. Smoldering multiple myeloma usually doesn't cause any symptoms.

Multiple myeloma. When plasma cells are cancerous and grow out of control, it's called multiple myeloma. These cancer cells build up in the bone marrow and crowd out healthy cells. They also make M proteins. Higher levels of M protein in the blood can lead to complications.

Waldenstrom's macroglobulinemia. This cancer affects small lymphocytes (white blood cells). In this blood cancer, plasma cells produce a particular type of sticky M protein called IgM monoclonal antibody.. A buildup of these proteins can thicken the blood and lead to symptoms, such as fatigue and weight loss.

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Complications of M Proteins

A lot of the time, M proteins don't cause any problems. You may not realize that you have them in your body. But as the abnormal or cancerous plasma cells spread, they may crowd out healthy blood cells. This can lead to complications, such as:

Anemia. Symptoms of anemia like shortness of breath is one of the more common presentations cause the BM is so crowded with abnormal plasma cells that red blood cells are crowded out. So are platelets that are formed in the bone marrow, so bruising is common.

Infections. When plasma cells make more M proteins, there are fewer functional antibodies to fight infections.

Peripheral neuropathy. M proteins can affect how well your nerves work. You can get numbness, tingling, or burning in your hands, feet, or lower legs.

Bone loss or damage. Bones are weakened by dysfunctional plasma cells, both cause of decreased bone density (bone loss) and because of actual collections of cancer cells in the bone. You can suffer from bone fractures from minimal activity (like a sneeze). This is called a pathologic fracture.

Kidney problems. Your kidneys have to work overtime to filter out the M proteins and calcium in your blood. Your kidneys might not work as well as they should, or you might even have kidney failure.

Types of M Proteins

M proteins are made of pieces called chains. There are usually two "light" chains and two "heavy" chains.

M proteins are grouped by what kind of heavy and light chains they have. There are five kinds of heavy chains, called IgG, IgA, IgD, IgM, and IgE. There are two types of light chains, called kappa and lambda.

The most common type of M protein in myeloma is IgG. High levels of IgM suggest you may have Waldenstrom's macroglobulinemia.

Tests for M Proteins

If your doctor suspects a disease or notices abnormal proteins on another test, they may want to test for M proteins. There are several types of tests:

Serum and urine protein electrophoresis (SPEP and UPEP). Your doctor places a sample of your blood or urine in a gel. An electric charge runs through it. This separates proteins based on their charge, which shows how much M protein you have. It usually shows a tall and narrow peak in the region of antibodies if there is an M protein present. You need a followup immunofixation (see below) to confirm if the peak is M protein and to identify the subgroup.

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Quantitative immunoglobulin testing (Qlg). This test measures the total amount of immunoglobulin proteins in your blood. It is useful to follow if you are found to have a monoclonal protein in your blood or urine.  An increasing amount  of M protein over time is one of the criteria for treatment or a change in treatment.

If you already know that you have M proteins, your doctor may use these tests to learn more about them. This may help better diagnose and treat your condition.

Immunofixation electrophoresis (IFE) of blood or urine. In this test, an electric charge separates the M proteins by type. This helps your doctor find out what kind of M proteins you have.

Serum free light chain assay. Sometimes, the light chains that are normally part of your M proteins instead float freely in your blood. This test looks for and measures these light chains.

WebMD Medical Reference Reviewed by Sabrina Felson, MD on September 16, 2021

Sources

SOURCES:

American Cancer Society: "What is Multiple Myeloma?"

American Society of Nephrology: "Clinical Tests for Monoclonal Proteins."

Canadian Cancer Society: "Multiple Myeloma."

Cleveland Clinic: "Monoclonal Gammopathy of Undetermined Significance (MGUS)."

Hematology/Oncology Clinics of North America: "Does My Patient With a Serum Monoclonal Spike Have Multiple Myeloma?"

International Myeloma Foundation: "Tests to Assess Monoclonal Protein," "Understanding MGUS and Multiple Myeloma."

Leukemia & Lymphoma Society: "Diagnosis," "Understanding Multiple Myeloma and Laboratory Values," "Waldenstrom Macroglobulinemia Facts."

Mayo Clinic: "Multiple Myeloma."

Multiple Myeloma Research Foundation: "Symptoms, Side Effects, and Complications."

University of California San Francisco Helen Diller Family Comprehensive Cancer Center: "About Multiple Myeloma."

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