During diseases like multiple myeloma, the body produces abnormal antibodies, including IgG or IgA antibodies. Tests that measure levels of these antibodies help diagnose myeloma, plan treatments, and predict outlook.
Antibodies are proteins made by plasma cells, a type of white blood cell. They protect the body from foreign substances (things that come from outside the body), such as bacteria, viruses, and allergens. Antibodies attach to these objects, signaling to the rest of the immune system to kill the germ or remove the foreign substance.
Each antibody can only recognize one specific target on the surface of the type of bacteria, virus, or other substance. Usually, the body contains many different plasma cells, each of which makes antibodies that target a different thing. Together, all of these individual antibodies can recognize a wide variety of substances.
Each antibody is made up of four smaller proteins. Two of these proteins are called light chains, and the other two are heavy chains. Antibodies are often classified based on which types of light chain and heavy chain proteins they contain.
There are five types of heavy chains. Antibodies containing each type are usually located in different parts of the body:
When plasma cells become damaged, they may turn cancerous. A single cancerous cell can make many copies of itself, leading to a buildup of abnormal plasma cells that crowd out the body’s healthy plasma cells. When this happens, it is known as multiple myeloma.
Cancerous plasma cells produce abnormal antibodies. Rather than making a variety of antibodies that can each fight off different substances, myeloma cells produce antibodies that are all the same. The abnormal antibodies are called M protein, myeloma protein, monoclonal protein, M spike, or paraprotein. M proteins can’t fight infection, may damage the kidneys and bones, and may lead to tumors.
Like normal antibodies, M protein contains two heavy chain and two light chain proteins. Multiple myeloma is grouped into categories based on which type of chain makes up the M protein. Cases of myeloma involving different types of M protein may have different outcomes and need different treatment plans.
IgG is the most common antibody type, and IgG myeloma is the most common type of multiple myeloma. About 1 out of 2 people with multiple myeloma have M protein that contains IgG. IgA is the second most common type of heavy chain seen in M protein. About 1 out of 5 people with myeloma have the IgA type. Less often, M protein can be made from IgD or IgE. IgM myeloma is very rare. If a person has M protein made from IgM heavy chains, they are more likely to have a condition called Waldenstrom macroglobulinemia, a type of lymphoma.
There are also other types of myeloma that don’t involve heavy chain protein. Some people with myeloma have light chain myeloma, also called Bence-Jones myeloma. In this case, plasma cells only make light chain protein and not heavy chain protein. Because light chains are smaller, they pass into urine and may not be discovered by blood tests. People can have nonsecretory myeloma, in which plasma cells don’t make any part of the M protein, but this is very rare.
Multiple myeloma diagnosis includes tests to determine whether plasma cells are making too much IgG, IgA, or another heavy chain protein. These tests may show which type of M protein a person has, or they may show the overall levels of the heavy or light chain proteins.
Knowing which type of heavy chain is found in M protein may help doctors estimate prognosis (outlook). People with IgA myeloma tend to have a worse prognosis than people with IgG myeloma. IgA myeloma leads to lower survival rates and a higher risk of relapse (the myeloma is more likely to come back after being treated). If you are at risk of having a poor outcome, your doctor may recommend more aggressive treatments.
Immunofixation electrophoresis (IFE), similar to another test called immunoelectrophoresis (IEP), is a test that is used to determine which heavy chain proteins make up M protein. IFE shows whether or not a certain abnormal heavy chain is present, but it doesn’t show the overall levels. IFE may be performed using either a blood sample or a urine sample. This test can be used at the beginning of diagnosis to determine which type of M protein a person has. It may also be used later on, after treatment. IFE test results can help confirm that treatment was successful and that no more M protein remains.
A quantitative immunoglobulins (QIg) test is another blood test that shows which chain is found within the M protein. This test shows the level of both normal and abnormal versions of each type of heavy chain and can be used to monitor the success of treatment. An immunoglobulin test is often used to screen for multiple myeloma in people who are at risk of developing the condition.
After the M protein type is determined with other tests, measuring M protein levels can have several purposes. At the beginning of diagnosis, knowing the amount of M protein helps doctors determine the myeloma stage. Doctors may also track M protein levels over time to find out whether a treatment is working.
Serum protein electrophoresis (SPEP) measures the overall amount of M protein present in the blood. Urine protein electrophoresis (UPEP) is a similar test but measures M protein in the urine. SPEP and UPEP can show whether a person has high or low levels of M protein. It can be hard to measure protein levels with SPEP, so some doctors use quantitative immunoglobulins testing to track disease over time for people with IgA myeloma.
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