What is being tested?
Beta-2-microglobulin (B2M) is a protein that is found on the surface of almost all cells in the body and is shed by cells into the blood, particularly by B lymphocytes and tumour cells. It is present in most body fluids and its level rises with conditions that increase cell production and/or destruction, or that activate the immune system. This test measures B2M in the blood, urine or rarely, in the cerebrospinal fluid (CSF).
B2M is frequently elevated in the blood with cancers such as multiple myeloma, leukaemia and lymphoma, with inflammatory disorders, infections (e.g. HIV, CMV) and in kidney disease. Because B2M is increased with blood cell cancers, it may be useful as a tumour marker. Though it can also be used to assess kidney function.
In the kidneys, B2M passes through blood filtering units, the glomeruli, and is then reabsorbed by the renal tubules - these are structures that reclaim water, proteins, vitamins, minerals and other substances that are useful to the body. Normally, only small amounts of B2M are present in the urine but when the renal tubules become damaged or diseased, concentrations increase due to the decreased ability of the tubules to reabsorb this protein. When the glomeruli in the kidneys are damaged, then they are unable to filter out B2M, so the level in the blood rises. In people with kidney disease who are undergoing dialysis, B2M can form long protein chains that can be deposited in joints and tissues, causing stiffness and pain. This condition is called B2M dialysis-associated amyloidosis.
B2M levels can be increased in the CSF of individuals with blood cell cancers that have spread (metastasised) to the brain, such as leukaemia and lymphoma, but also with some chronic disorders such as multiple sclerosis, and with viral infections such as HIV.
How is it used?
The characteristics of beta-2-microglobulin (B2M) make it useful as a tumour marker for some blood cell cancers, for detecting kidney damage and for distinguishing between glomerular and tubular disorders of the kidney. B2M is not diagnostic for a specific disease but it has been associated with the amount of cancer present (tumour burden) and it gives additional information about someone's likely prognosis and about the health of their kidneys.
As a tumour marker: a blood B2M test may be ordered to help determine the severity and spread (stage) of multiple myeloma and may sometimes be ordered to evaluate the effectiveness of treatment. Elevated B2M in the blood is correlated with a larger amount of tumour (tumour mass) and reduced kidney function in multiple myeloma patients. The International Myeloma Working Group has published guidelines called the International Staging System for Multiple Myeloma. The staging system is based mainly off levels of both albumin and B2M in the blood. Higher blood B2M levels correspond with higher disease stages and therefore more advanced disease with worse prognosis. B2M can be ordered to help evaluate the prognosis of cancers such as leukaemia and lymphoma.
In kidney disease: both blood and urine B2M tests can be ordered along with other kidney function tests such as urea, creatinine, and albumin/creatinine ratio to evaluate kidney damage and disease and to distinguish between disorders that affect the glomeruli and the renal tubules. B2M tests can sometimes be ordered to monitor people who have had a kidney transplant, to detect early signs of rejection. Excess B2M can accumulate in joint spaces (synovitis) in long-term dialysis; this is called dialysis-related amyloidosis (DRA). A B2M test may be used to help evaluate a person for DRA. It may also be ordered to monitor people who are exposed to high levels of cadmium and mercury, such as in the case of occupational exposure.
Rarely, a CSF B2M test can be ordered to assess a disease's central nervous system (brain) involvement. The B2M test is not typically ordered to detect or monitor B2M dialysis-related amyloidosis, to monitor inflammatory conditions, or to monitor HIV.
When is it requested?
A B2M test may be ordered during the initial workup of a person who has been diagnosed with multiple myeloma in order to stage the disease and periodically to monitor the effectiveness of treatment. It may sometimes be ordered when a person has leukaemia or lymphoma to help determine their likely prognosis.
Both blood and urine B2M tests may be ordered when a person has symptoms associated with kidney dysfunction and the doctor wants to distinguish between disorders that affect the glomeruli and the renal tubules. Some signs and symptoms may include:
A urine test may also be ordered periodically to monitor a person who has had a kidney transplant and to monitor those exposed to high concentrations of cadmium or mercury. Dialysis-related amyloidosis is primarily diagnosed by tissue or bone biopsy. B2M levels are performed as part of the work-up in addition to imaging studies.
A CSF B2M may rarely be ordered when a doctor suspects that a disease such as leukaemia or lymphoma is affecting the central nervous system (brain).
What does the result mean?
Increased levels of B2M in the blood and urine indicate that there is a problem, but they are not diagnostic of a specific disease or condition. They do reflect disease activity and tumour burden, if cancer is the case of the elevated concentration. When a person has been diagnosed with multiple myeloma, leukaemia, or lymphoma, they are likely to have a poorer prognosis if their blood B2M levels are significantly elevated. For monitoring treatment, decreasing concentrations in someone with multiple myeloma indicate that a person is responding to treatment. Stable or increasing levels indicate that the person is not responding.
In someone with signs of kidney disease, increased levels of B2M in the blood and low levels in the urine indicate that the disorder is associated with glomerular dysfunction. If B2M is low in the blood and high in the urine, then it is likely that the person has renal tubule damage or disease. In a person who has been on long-term dialysis, an increase in B2M is associated with dialysis-related amyloidosis. Increases in urine B2M in a person with a kidney transplant may indicate early kidney rejection. Increases in someone who is exposed to high levels of cadmium or mercury may indicate early kidney dysfunction.
Increases in the CSF in someone with a disease such as leukaemia or HIV/AIDS indicates likely central nervous system involvement.
Low levels of B2M are considered normal. B2M may be undetectable in the urine and CSF.
Is there anything else I should know?
Conditions associated with an increased rate of cell production or destruction, severe infections, viral infections such as CMV (cytomegalovirus), and some conditions that activate the immune system, such as inflammatory conditions and autoimmune disorders, can cause increases in B2M levels, but the test is not typically ordered to monitor these conditions.
Drugs such as lithium, cyclosporine, cisplatin, carboplatin, and aminoglycoside antibiotics can increase B2M blood and/or urine concentrations by causing kidney damage primarily.
Recent nuclear medicine procedures and radiographic contrast media can affect test results.
Common questions
Most people will never have a B2M test done. It is not intended, or useful, for a general population screen.
No, the test requires specialised equipment and training and is not available in every laboratory. Your blood or urine may be sent to a reference laboratory.
In most cases, the sample tested will be dictated by the reason that the test is being performed which is usually a blood sample when B2M is being used as a tumour marker for haematological malignancies e.g. multiple myeloma. It may be necessary to do a blood test, a urine test, or both together. The results are not generally interchangeable. In certain neurological situations, cerebrospinal fluid (CSF) may also be tested.
Generally, no. If yo work with or suspect that you have been exposed to cadmium or mercury, then your doctor will order specific tests for cadmium or mercury in your blood and/or urine.
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