Beta-2 microglobulin

Beta-2 microglobulin (β2-microglobulin or β2M) is a component of MHC class I molecules, which are present on all nucleated cells (excluding red blood cells). Its primary function is to regulate the immune system. Beta-2 microglobulin plays a critical role in cell-mediated immunity by presenting peptide fragments derived from pathogens to T cells. It is a low-molecular-weight protein (11.8 kDa) encoded by the B2M gene on chromosome 15.

Structure and Function

Beta-2 microglobulin is a globular protein that forms the light chain of the MHC class I molecule. It is non-covalently linked to the α-chain of the MHC class I molecule. This complex is vital for the immune system to recognize foreign molecules in the body, leading to the destruction of infected cells by T cells. The stability and surface expression of MHC class I molecules are dependent on the presence of β2-microglobulin.

Clinical Significance

Elevated levels of β2-microglobulin can be found in the blood and urine of patients with various diseases, indicating renal failure, inflammation, or malignancies such as multiple myeloma and some lymphomas. It is used as a tumor marker for some of these conditions. In kidney disease, especially, β2-microglobulin levels are monitored as it is cleared by the kidneys, and high levels can indicate renal dysfunction.

Dialysis

In patients undergoing dialysis, β2-microglobulin can accumulate due to its reduced clearance, leading to dialysis-related amyloidosis. This condition is characterized by the deposition of β2-microglobulin amyloid fibrils in joints and bones, causing pain and stiffness.

Amyloidosis

β2-microglobulin is also involved in the pathogenesis of amyloidosis, where its misfolded proteins aggregate and deposit in tissues, leading to organ dysfunction. This condition can be systemic or localized and requires careful management to prevent progression.

Genetics

The gene encoding β2-microglobulin is located on chromosome 15 (15q21-q22.2). Mutations in this gene are rare but can lead to a deficiency in β2-microglobulin, affecting the immune system's ability to function properly.

Measurement

The concentration of β2-microglobulin can be measured in blood, urine, and cerebrospinal fluid (CSF) using immunoassay techniques. These measurements can help in diagnosing and monitoring the progression of diseases associated with elevated β2-microglobulin levels.

Treatment and Management

Treatment of conditions associated with high levels of β2-microglobulin focuses on the underlying disease. In the case of dialysis-related amyloidosis, improving dialysis efficiency and switching to high-flux membranes can reduce β2-microglobulin levels. Pharmacological treatments, including biologics, may be used to manage conditions like multiple myeloma.