Beta-2 Microglobulin: An Overview

Background

Beta-2 microglobulin (B2M) is a small protein found in all nucleated cells, including macrophages and active B and T lymphocytes.

It is released into circulation during normal cell turnover, and serum levels increase with conditions of increased turnover, including hematological, oncological, and rheumatological disease. Beta-2 microglobulin is important in maintaining serum albumin levels, participates in immune antigen presentation, and interacts with several protein cofactors involved in mucosal immunity, iron metabolism, immunoglobulin homeostasis, and tumor surveillance. The kidney clears it, and decreased renal function is associated with elevations of serum and urine B2M (Argyropoulos 2017).

Increased B2M is often associated with malignancy, severe inflammatory disorders, and chronic infection. However, levels may also increase with decreased kidney function and can help differentiate glomerular from tubular dysfunction. Glomerular disease is characterized by elevated serum B2M and low urine B2M, while tubular disease is characterized by low serum B2M and elevated urine B2M. Beta-2 microglobulin was initially discovered in the urine of subjects with cadmium toxicity and is still used to detect renal toxicity caused by drugs or heavy metals. Renal excretion can increase by 100-1000 times normal with cadmium exposure. Beta-2 microglobulin differs from beta-2 globulins such as fibrinogen (Pagana 2022).

Elevated serum B2M is associated with increased cardiovascular risk, arterial calcification, malnutrition, inflammation, and atherosclerosis in those with kidney disease. High-flux hemodialysis can remove B2M and reduce morbidity and mortality risk. Levels can increase with malignancy despite normal renal function, and higher serum levels are associated with poorer prognosis in those with leukemia, lymphoma, multiple myeloma, and cancer of the ovaries, gallbladder, prostate, breast, and kidney (Argyropoulos 2017).

Increased serum levels (Pagana 2022, Argyropoulos 2017)

• Autoimmune disorders, including Crohn’s, Sjogren’s, lupus, and rheumatoid arthritis
• Chronic inflammatory processes
• Glomerular renal disease
• Kidney transplant rejection
• Lymphomas, leukemia, myeloma
• Proteinuria
• Smoking
• Solid organ malignancies
• Viral infections, especially HIV and cytomegalovirus

Increased in urine (Pagana 2022)

• Drug-induced renal toxicity
• Heavy metal-induced renal disease
• Lymphomas, leukemia, myeloma
• Renal tubule disease

There is currently no specific optimal range for serum B2M. However, the following standard ranges have been utilized:

• Quest: Beta-2-Microglobulin, Serum Range   Adults ≤2 .51 mg/L
• Labcorp: Beta-2 Microglobulin, Serum Range 0.6 - 2.4 mg/L
• Pagana: Beta2-microglobulin: Blood: 0.7-1.8 mcg/mL (mg/L), Urine: ≤ 300 mcg/L (mg/L)

Optimal Takeaways

• Beta-2 microglobulin is found at relatively low levels in serum and urine.
• Elevations may be associated with malignancy, activation of cellular immunity, or reduced kidney function.
• B2M is utilized as a marker of disease risk and prognosis, especially in malignancies and kidney disease

References

Argyropoulos, Christos P et al. “Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases.” Frontiers in medicine vol. 4 73. 15 Jun. 2017, doi:10.3389/fmed.2017.00073 This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

Labcorp Beta-2 Microglobulin, Serum https://www.labcorp.com/tests/010181/sub-2-sub-microglobulin https://files.labcorp.com/testmenu-d8/sample_reports/010181.pdf

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.

Quest Beta-2-Microglobulin, Serum Range https://testdirectory.questdiagnostics.com/test/test-detail/852/beta-2-microglobulin-serum?cc=MASTER