Serum protein electrophoresis (SPEP) is a blood test that separates the proteins in your blood into groups and measures how much protein is in each group. Doctors most often order it to look for an abnormal antibody called a monoclonal protein, or M protein. A single group makes an M protein from abnormal plasma cells. SPEP is used to find and follow conditions such as monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Your report may list the test as SPEP, serum protein electrophoresis, or protein electrophoresis, serum.
This article explains what serum protein electrophoresis measures, what an M protein is, what your SPEP results mean, and what tests and follow-up usually come next.
The reference range that applies to your result is the one printed on your laboratory report, not the typical ranges shown here. Reference ranges vary between laboratories based on the equipment used, the population tested, and individual factors such as age, sex, and pregnancy status. Always compare your result to the reference range printed on your own report, and discuss any abnormal (or unexpectedly normal) result with your doctor.
What does the serum protein electrophoresis test measure?
Serum protein electrophoresis measures the proteins in serum, the liquid part of the blood after the cells are removed. The test sorts these proteins into five main groups, called fractions. Many laboratories also report total protein, which is the sum of all the fractions. A typical adult range for total protein is approximately 6.0 to 8.3 g/dL (60 to 83 g/L). Typical adult ranges for each fraction are approximately:
- Albumin. 3.5 to 5.0 g/dL (35 to 50 g/L). Albumin is the largest fraction. The liver makes it, and it helps keep fluid in the blood vessels.
- Alpha-1 globulins. 0.1 to 0.3 g/dL (1 to 3 g/L). These are mostly proteins made by the liver, including some that rise with inflammation.
- Alpha-2 globulins. 0.6 to 1.0 g/dL (6 to 10 g/L). These include proteins that rise with inflammation and some that carry other substances in the blood.
- Beta globulins. 0.7 to 1.2 g/dL (7 to 12 g/L). These include the protein that carries iron and some antibodies.
- Gamma globulins. 0.7 to 1.6 g/dL (7 to 16 g/L). This fraction contains most of the body’s antibodies, also called immunoglobulins. Most M proteins appear here.
Some laboratories report each fraction as a percentage of total protein instead of in g/dL or g/L.
What is an M protein on serum protein electrophoresis?
On serum protein electrophoresis, the results are shown as a graph with a peak for each fraction. Normally, the antibodies in the gamma fraction are made by millions of different plasma cells. Because they are all slightly different, they spread out and form a broad, gentle hump on the graph.
When a single group of abnormal plasma cells makes large amounts of one identical antibody, that antibody collects in one spot and forms a tall, narrow peak called an M protein, M spike, or monoclonal band. “Monoclonal” means the antibody came from one family of cells. Your report will say whether an M protein is present and, if so, give its size in g/dL or g/L. A very small M protein may be reported as “trace” or “too small to quantify.”
Finding an M protein does not mean you have cancer. Most people with an M protein have MGUS, a condition that causes no symptoms and usually does not need treatment.
How is the serum protein electrophoresis test performed?
Serum protein electrophoresis uses a standard blood sample taken from a vein in your arm. Fasting is usually not needed. In the laboratory, the serum is placed in a gel or a thin tube, and an electric current is applied. Proteins move at different speeds depending on their size and electrical charge, separating them into fractions. A laboratory physician or pathologist often reviews the pattern and adds a brief interpretation to the report.
What do serum protein electrophoresis results mean?
Your SPEP report may describe several different patterns:
- Normal pattern. All fractions are within the reference range, and no M protein is seen. This makes a plasma cell disorder that produces an M protein unlikely, although a few conditions are possible and require additional tests.
- M protein present. A narrow peak, usually in the gamma fraction, shows an abnormal antibody from one group of plasma cells. Further testing is needed to identify its type and the cause.
- Broad increase in gamma globulins. A wide rise across the gamma fraction is called a polyclonal increase. It means many normal plasma cells are making extra antibodies, usually in response to long-term infection, inflammation, autoimmune disease, or liver disease.
- Low gamma globulins. A low gamma fraction means the body is making fewer antibodies than usual. This can increase the risk of infection, and it has many causes, including some blood cancers.
- Low albumin. A low albumin level can reflect liver disease, kidney disease that causes protein loss in the urine, inflammation, or poor nutrition.
A result slightly outside the reference range is often not significant on its own. Your doctor will consider the overall pattern.
What conditions can cause an M protein on serum protein electrophoresis?
Several conditions can cause an M protein. The size of the M protein, measured on SPEP, is one of the features used to tell them apart:
- Monoclonal gammopathy of undetermined significance. MGUS is the most common cause. The M protein is less than 3 g/dL (30 g/L), and there are no signs of organ damage. The chance of MGUS progressing to a blood cancer is approximately 1% per year. The risk is lowest when the M protein is under 1.5 g/dL (15 g/L), is IgG, and the free light chain test is normal.
- Smoldering multiple myeloma. The M protein is 3 g/dL (30 g/L) or more, or the bone marrow contains more abnormal plasma cells. There are still no signs of organ damage.
- Multiple myeloma. Abnormal plasma cells can cause anemia, kidney damage, high calcium, or bone damage. The M protein is often, but not always, large.
- Other conditions. An M protein can also result from AL amyloidosis and some lymphomas. One example is lymphoplasmacytic lymphoma, which usually makes an IgM type of M protein.
What other tests are ordered with serum protein electrophoresis?
Serum protein electrophoresis shows whether an M protein is present but does not identify its type. It is usually ordered with other tests:
- Immunofixation. This test identifies the antibody and light chain type in the M protein, such as IgG kappa or IgA lambda. It can also find small M proteins that SPEP misses.
- Serum free light chains. This test measures kappa and lambda light chains that are not attached to a full antibody, and the ratio between them. Many laboratories consider a ratio of approximately 0.26 to 1.65 typical. It can find conditions in which the plasma cells make only light chains, which may not appear on SPEP.
- Quantitative immunoglobulins. This test measures total IgG, IgA, and IgM in the blood.
- Urine protein electrophoresis. This test looks for light chains, called Bence Jones protein, in the urine.
- Tests for organ damage. A complete blood count, kidney function tests, and a calcium level help show whether an M protein is causing problems.
What happens after a serum protein electrophoresis test?
If no M protein is found and the other fractions are normal, you usually don’t need further testing. If a broad increase or another pattern is found, your doctor will look for its cause.
If an M protein is found, the next steps depend on its size, its type, and the results of the other tests. People with low-risk MGUS are usually followed with repeat blood tests, often first after about six months and then less often. People with a larger M protein, a non-IgG type, an abnormal free light chain ratio, or signs of organ damage are often referred to a hematologist. A bone marrow biopsy and imaging may be recommended to look for smoldering or active multiple myeloma.
Questions to ask your doctor
- Was an M protein found on my serum protein electrophoresis?
- How large is the M protein, and what type is it?
- Were immunofixation and serum free light chain tests done?
- Do I have MGUS, smoldering myeloma, or another condition?
- What is my risk of the M protein progressing to a blood cancer?
- Do I need a bone marrow biopsy or imaging?
- Should I see a hematologist?
- How often should I repeat my SPEP?
- What symptoms should prompt me to contact you sooner?
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