Wondering how doctors diagnose multiple myeloma? Serum protein electrophoresis (SPEP) is a crucial tool. This blood test measures abnormal levels of monoclonal proteins, or M proteins, which may be linked to multiple myeloma and other conditions.

Learning more about SPEP, including how it’s done, what to expect, and how to interpret the results, can help you feel better informed and more in control of what’s happening with your myeloma.

How Does SPEP Work?

SPEP measures unusual proteins in the blood, especially M proteins and antibodies (immunoglobulins), which are proteins the immune system makes to help fight infections. Plasma cells produce these proteins, including immunoglobulin G, immunoglobulin A, and immunoglobulin M (IgM), as part of the body’s immune response.

In some cases, the test is done using a urine sample, known as urine protein electrophoresis. We’ll talk more about this later. Another test commonly used alongside SPEP is immunofixation electrophoresis (IFE), which helps doctors further understand abnormal protein levels in the blood.

Blood serum is the liquid part of blood that remains after clotting agents are removed. When a person’s blood is brought to the laboratory for analysis, it’s separated into different components, including serum, and different kinds of tests can be run on each component.

Proteins Measured by SPEP

SPEP measures levels of five protein types:

• Albumin
• Alpha-1 globulin
• Alpha-2 globulin
• Beta-globulin
• Gamma-globulin

Each protein moves at its own speed and groups together when exposed to an electric current, creating specific patterns. As part of the test process, each component is separately examined and compared with amounts that are found in healthy individuals. Their patterns are also checked for any differences from normal results.

When Is SPEP Used?

Doctors may order an SPEP test if you show signs of unusual protein levels in the blood that may be linked to multiple myeloma. A test called urine protein electrophoresis might be used if doctors suspect that light chains (Bence-Jones proteins) are being lost in your urine.

Some of these signs and symptoms include:

• Abnormal episodes of fatigue, constipation, or nausea
• Confusion
• Headaches
• Seizures
• Vision problems
• Carpal tunnel syndrome
• Frequent fractures or bone pain
• Unusual bruising or bleeding
• Repeated infections
• Anemia (low hemoglobin levels) without any other identifiable cause

In some cases, a person may show no symptoms. Instead, their health care team may first notice a problem when laboratory results indicate high levels of protein in their blood or urine. A doctor may also notice hypercalcemia (high calcium levels) in a person’s blood and order more tests to find the cause.

How Do You Take an SPEP Test?

Preparing for SPEP involves largely the same process as going in for other blood tests and laboratory testing. You may need to temporarily stop taking some medications, depending on your doctor’s advice. You won’t typically have to do anything further before your appointment.

A medical professional will take a blood sample, which will then be processed by the laboratory. The lab technicians will measure the amount of each protein and consider the results alongside your other signs and symptoms.

Normal SPEP Results

SPEP results are measured in grams per deciliter (g/dL), although reference ranges may vary. For adults, the typical reference ranges are:

• Total protein — 6.4 to 8.3 g/dL
• Albumin — 3.5 to 5.0 g/dL
• Alpha-1 globulin — 0.1 to 0.3 g/dL
• Alpha-2 globulin — 0.6 to 1.0 g/dL
• Beta-globulin — 0.7 to 1.2 g/dL
• Gamma-globulin — 0.7 to 1.6 g/dL

These SPEP ranges help doctors diagnose conditions like multiple myeloma or decide which tests are needed for further investigation.

What Do SPEP Results Tell Doctors?

SPEP results do not provide a definitive diagnosis of multiple myeloma. Your doctors will take several different factors into account alongside your results to come to a diagnosis.

Low Levels

Low levels of total serum protein could signal the following issues:

• Malnutrition
• Kidney disease
• Nephrotic syndrome (kidneys leak too much protein into the urine)
• Liver disease
• Cirrhosis (scarring of the liver)
• The inability of the digestive system to absorb and process protein

A decrease in beta-globulin may cause malnutrition or low levels of cholesterol.

Elevated Levels

In cases of elevated protein levels, such as higher gamma-globulin, doctors may suspect blood cancers like multiple myeloma, lymphoma, or inflammatory diseases. They may also indicate a less serious condition related to myeloma — monoclonal gammopathy of undetermined significance (MGUS).

A higher-than-normal alpha-2 globulin level may mean acute or chronic inflammation.

An increase in beta-fraction globulin and its components (C3, transferrin, and beta-lipoprotein) may be due to hormonal medications or the body’s inability to break down fats.

A spike in gamma-globulin protein may indicate:

• Blood cancers such as multiple myeloma
• Liver disease
• An infection
• Inflammatory disease

Talk to Your Doctor

Your medical history and any medications you take can affect your SPEP results, so your health care team will consider these factors when interpreting the lab values. Although SPEP and IFE tests provide insight into abnormal protein levels, they don’t pinpoint the exact cause. Depending on your results, your medical team may order additional tests, such as a bone marrow biopsy or other blood tests, to confirm a diagnosis or explore other potential causes. If results suggest multiple myeloma, you may be referred to an oncology specialist.

Find Your Team

MyMyelomaTeam is the social network for people with myeloma and their loved ones. On MyMyelomaTeam, more than 26,500 members come together to ask questions, give advice, and share their stories with others who understand life with myeloma.

Did you have an SPEP test as part of your diagnosis for multiple myeloma? Do you have advice for others going through testing? Share your tips and experiences in a comment below or on your Activities page.