Beta-2 Microglobulin

Beta2 Microglobulin is a protein that exists on the surface of all nucleated cells including White Blood CellsBeta2 Microglobulin is a human leukocyte antibody (HLA) major histocompatibility antigen that exists with increased numbers on white blood cells (WBCs) and particularly on lymphatic cells. Production of this protein is increased as these cells are produced or destroyed. Therefore, β2M are increased in patients with malignancies (especially lymphoma, leukemia, or multiple myeloma) or in patients with chronic severe inflammatory diseases. Because the degree of elevation can be related to tumor cell load, β2M is an accurate measurement of tumor disease activity, stage of disease, and prognosis. In that light, it is an important tumor marker. When central nervous system (CNS) involvement with these neoplasms is suspected, β2M can be measured in the CNS fluid and compared to blood levels. Increased levels are diagnostic of CNS involvement.


Beta2 Microglobulin test is used as a tumor marker for blood tumors such as lymphoma or leukemia. This protein can also be used in the differential diagnosis of diseases of the kidney.


Blood levels are increased in patients with human immune deficiency virus (HIV) and are a measure of the disease activity. Cytomegalovirus infection is also associated with increased blood levels.


β2M is excreted by the glomeruli and partially reabsorbed into the blood by the renal tubule. In a patient with renal disease, when blood and urine β2M levels are obtained simultaneously, one can differentiate glomerular from tubular disease. In glomerular disease, blood levels are high and urine levels are low. In tubular disease, the blood levels are low and urine levels are high. Blood levels increase early in kidney transplant rejection.

In patients with aminoglycoside toxicity, β2M become elevated even before creatinine. Increased urine levels are found in patients with kidney disease caused by high exposure to heavy metals, such as cadmium or mercury. Periodic testing is performed on these workers to detect kidney disease at its earliest stage.



When Radioimmunoassay (RIA) methods are used to measure Beta-2 Mircroglobulin levels, the results could be  inaccurate if the patient had a recent nuclear imaging.





Normal Beta-2 Microglobulin Levels

In Blood: Between 1.1 mg/L and 2.4mg/L.

In Cerebrospinal Fluid: None or less than 2.4 mg/L.

In Urine: None or less than 160 mcg/L




Causes High Beta-2 Microglobulin Levels

  • AIDS.
  • Different types of Lymphomas.
  • leukemia.
  • Myeloma.
  • Glomerulonephritis (Glomerular Renal Disease): Is a group of diseases are associated with increased production and destruction of lymphocytes or other marrow cells.
  • Renal transplant rejection: Because excretion of β2M is renal, renal rejection reduces excretion and blood levels of β2M increase.
  • HIV, Cytomegalovirus (CMV), and other viral infections.
  • High Beta-2 Microglobulin Levels are also associated with Chronic Inflamtion. However, the pathophysiology behind this process is not well understood. In this case, Beta-2 Microglobulin may act as an acute phase reactant.




High Beta-2 Microglobulin Levels In Cerebrospinal Fluid

When Beta-2 Microglobulin high levels are found in the Cerebrospinal Fluid (CSF) this would be a strong indication that the central nervous system is involved with any of the following conditions:

  • Different types of Lymphomas.
  • Leukemia
  • HIV infection.
  • Multiple Sclerosis.




Measuring Beta-2 Microglobulin Levels in Urine

To measure Beta-2 Microglobulin levels in urine, the patient is required to collect urine for a 24 hours period. During those 24 hours, the patient is required to collect voided (clean) specimens in order to avoid any matters that may affect the test results. It is recommended that the patient drink a lot of water and fluids to help passing as much B2M out with urine and have more accurate results. It is also recommended to collect the last specimen as close as possible to the end of the 24 hour period.


Beta-2 Microglobulin is unstable in highly acidic urine which causes misleading lower B2M levels to be measured.




Causes of High Beta-2 Microglobulin Levels in Urine

High Beta-2 Microglobulin levels occurs when the body experience high levels of production and destruction of lymphocyte cells and other bone marrow cells. Also, when high B2M levels are found in blood, this will cause increased renal production of Beta-2 Microglobulin which exceeds the ability of renal tubule to absorb B2M leading to high B2M levels in urine.


High Beta-2 Mircroglobulin levels are caused by any of the following conditions:

  • AIDS.
  • Different types of Lymphomas.
  • leukemia.
  • Myeloma.
  • Renal Tubule Disease due to the renal tubule’s inability of absorbing excessive B2M.
  • Drug-induced Renal Toxicity.
  • Heavy Metal Induced Renal Disease.