M-protein (monoclonal protein) is the output of myeloma cells in most people with multiple myeloma. The serum protein electrophoresis (SPEP) test and urine protein electrophoresis (UPEP) measure the amount of monThis important group of blood and urine tests is used specifically for assessing the amount and activity of myeloma. They do so by measuring the monoclonal protein that myeloma cells secrete into the blood and/or urine
Serum and Urine Protein Electrophoresis (SPEP and UPEP)
Serum protein electrophoresis (SPEP) is a test that measures the amount of heavy chain monoclonal protein made by myeloma cells. Learn more at Types of Myeloma.
SPEP separates all the proteins in the blood according to their electrical charge. Urine protein electrophoresis, or UPEP, does the same thing for proteins in the urine.
The right-hand graph represents a normal SPEP result. It shows a peak in the measurement of albumin, which is the most plentiful protein in the blood, and lower levels of the other proteins, grouped into areas labeled alpha 1 and 2, beta (with two bumps also known as 1 and 2), and gamma, which is where the antibody proteins, including those made by myeloma cells, would lie on the graph.
The left-hand graph represents the result for a patient with myeloma. In addition to the spike for albumin, there is another tall spike indicated by the red arrow in the gamma region of the graph. The area under that spike, or curve, can be measured. The pathologist measures the area under that curve and then subtracts the normal level of gamma globulins from the total, and that is your level of monoclonal protein (M-protein).
SPEP and UPEP tell us how MUCH monoclonal protein there is, but not the type. While monoclonal protein is the output of myeloma cells in most people with myeloma, every person’s myeloma is unique. The output (monoclonal protein) can vary in amount from patient to patient and can vary in how that amount relates to the behavior of the myeloma. SPEP and UPEP don't directly measure myeloma cells; they measure the output of myeloma cells. People’s myeloma cells don’t reproduce at the same rate or secrete the same amount of protein per cell.
A caveat with SPEP is that immunoglobulin A-type (IgA) myeloma monoclonal protein does not separate out in the gamma region of the graph, but can get “stuck” with the beta or even alpha proteins. Patients with IgA heavy chains should discuss the best way to measure their monoclonal protein with their doctors.
Immunofixation Electrophoresis of Blood or Urine (IFE)
Immunofixation electrophoresis of blood or urine (IFE) is the counterpart to SPEP and UPEP. IFE tells us the TYPE of monoclonal protein in the blood and/or urine but not the amount. IFE testing separates proteins by electrical charge. IFE measures only the monoclonal — or abnormal —proteins, not the normal (polyclonal) ones
The result is either negative or positive for the presence of a particular type of monoclonal protein.
Darzalex can influence the results of IFE if a patient has IgG Kappa myeloma and is being evaluated for complete response. The patient may be in a very deep complete response, but a tiny band of IgG Kappa will show up on the test.
Quantitative Immunoglobulin Testing or QIg
Quantitative immunoglobulins testing is often done as part of early screening for MM. It is usually done if the total protein level is elevated. QIg measures total immunoglobulin protein in the blood, both normal and abnormal. If an increase an immunoglobulin is detected by QIg, further testing with IFE is required to see if the increase is from abnormal (monoclonal) protein.
Some doctors also use QIg to follow patients with IgA myeloma because it's difficult to assess IgA with SPEP.
Serum Free Light Chain Assay, or Freelite® testing
The serum free light chain assay (brand name Freelite®) is used for diagnosis and monitoring of myeloma. Immunoglobulin proteins are made up of two kinds of molecules, heavy chains and light chains (see diagram). These heavy and light chains are usually bound together as “intact immunoglobulins.” For reasons we do not know, however, the plasma cells produce more light chains than heavy chains, and the excess, or unbound, light chains circulate freely in the blood. They are therefore called “free” light chains, and they are present in both healthy individuals and in patients with myeloma and related disorders (MGUS, SMM, amyloidosis, light chain deposition disease, and Waldenström’s macroglobulinemia).
Some patients’ myeloma cells secrete both heavy and light chains, some only heavy chains, and some only light chains. Some patients, when assessed by SPEP, appear to secrete no M-protein at all because their myeloma cells secrete no heavy chain protein, only light chains. The Freelite test is used for patients who only secrete light chains (this is often called “Bence-Jones myeloma,” named after the doctor who first found and identified light chain protein in the urine), for patients who secrete both heavy and light chains, and for patients who secrete very low levels of protein (this is called “oligosecretory myeloma”)
The Freelite assay is also used in the diagnosis and monitoring of patients who have MGUS, a non-cancerous elevation in monoclonal protein, to assess their risk of developing active myeloma. Similarly, the Freelite test is used to monitor patients with smoldering or asymptomatic myeloma (SMM). For more information, read also Understanding MGUS and Smoldering Myeloma.
Serum Heavy/Light Chain Assay, or Hevylight® Test
The Hevylite® assay is a blood test that measures the intact immunoglobulins. Not only does it measure the intact heavy and light chain protein made by the myeloma cells, it also separately measures the heavy- and light-chain-bound immunoglobulin protein made by normal plasma cells. If your myeloma protein is, for example, IgA kappa, the intact immunoglobulin that is its normal counterpart will be IgA lambda
When you have active myeloma, your ability to make normal immunoglobulins (antibodies) is decreased. The Hevylite test not only measures the immunoglobulins made by myeloma cells, but is useful to detect early decreases in the number of normal antibodies. The test is also often used to measure IgA heavy chain protein because IgA is sometimes difficult to assess with SPEP.