Beta-2-Microglobulin

Overview:

Evaluate the severity and prognosis of multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma; detect kidney damage and distinguish between glomerular and tubular kidney disorders.

Drugs such as lithium, cyclosporine, cisplatin, carboplatin, and aminoglycoside antibiotics can increase ß2-microglobulin concentrations.1

ß-2microglobulin (ß2MG) is a small membrane protein that is a component of the class I major histocompatibility complex found on the surface of all nucleated cells.1 ß2MG is especially abundant on the surface of white blood cells so increased production or destruction of these cells causes serum levels to increase.1 Levels of ß2MG can be increased in patients with chronic inflammation, some viral infections, and in several hematologic malignancies associated with the ß-lymphocyte lineage.1

Serum ß2MG is often measured to assess the severity of multiple myeloma and Waldenström's macroglobulinemia and to monitor the effectiveness of treatment.2-4 Significantly elevated levels are associated with a poorer prognosis.2-4 Greipp and associates devised a simple calculation (the International Staging System) using serum ß2MG and albumin for the classification and stratification of patients with multiple myeloma.3 The utility of this calculation has been reviewed along with the potential for enhancement by addition of other biomarkers.4 Measurement of serum ß2MG is also helpful in patients with leukemia or lymphoma to help determine stage of disease and independent predict progression-free survival.5-10 ß2MG levels also rise during infection with some viruses, including cytomegalovirus and human immunodeficiency virus.11,12

In the healthy kidney, ß2MG passes through the glomeruli, and is then almost completely reabsorbed by the proximal tubules.1 In someone with signs of kidney disease, measurement of serum and urine ß2MG can be useful in distinguishing between glomerular and tubular disfunction. Serum ß2MG levels increase with the progression of chronic kidney disease.13 In patients on long-term hemodialysis, ß2MG can aggregate into amyloid fibers that deposit in joints and tissues, causing stiffness and pain in a condition referred to as dialysis-related amyloidosis.13 Serum ß2MG levels are a significant predictor of mortality in haemodialysis patients.14-17

Recently, serum ß2MG has been shown to be an independent predictor of mortality in older adults.18 This study found that increased baseline serum ß2MG was an independent predictor of increased cardiovascular events and cardiac mortality.18

1. Lab Tests Online. Beta-2 Microglobulin. Available at: http://www.labtestsonline.org/understanding/analytes/beta_microglob/related.html.

2. Kyle RA, Treon SP, Alexanian R, et al. Prognostic markers and criteria to initiate therapy in Waldenström's macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. Semin Oncol. 2003 Apr; 30(2):116-120. PubMed 12720119

3. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20; 23(15):3412-3420. PubMed 15809451

4. Kyrtsonis MC, Maltezas D, Tzenou T, Koulieris E, Bradwell AR. Staging systems and prognostic factors as a guide to therapeutic decisions in multiple myeloma. Semin Hematol. 2009 Apr; 46(2):110-117. PubMed 19389494

5. Molica S, Mauro FR, Callea V, et al. The utility of a prognostic index for predicting time to first treatment in early chronic lymphocytic leukemia: The GIMEMA experience. Haematologica. 2010 Mar; 95(3):464-469. PubMed 19903673

6. Tsimberidou AM, Wen S, O'Brien S, et al. Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2007 Oct 10; 25(29):4648-4656. PubMed 17925562

7. Wierda WG, O'Brien S, Wang X, et al. Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood. 2007 Jun 1; 109(11):4679-4685. PubMed 17299097

8. Jacobs P, Wood L. Chronic lymphocytic leukaemia—the haematologic basis for diagnosis and treatment. Hematology. 2002 Feb; 7(1):33-41. PubMed 12171775

9. Hallek M. Wanders L, Ostwald M, et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk Lymphoma. 1996 Aug; (5-6):439-447. PubMed 8882957

10. Di Giovanni S, Valentini G, Carducci P, Giallonardo P. Beta-2-microglobulin is a reliable tumor marker in chronic lymphocytic leukemia. Acta Haematol. 1989; 81(4):181-185. PubMed 2502891

11. Matos AC, Durão MS Jr, Pacheco-Silva A. Serial beta-2 microglobulin measurement as an auxilliary method in the early diagnosis of cytomegalovirus infection in renal transplant patients. Transplant Proc. 2004 May; 36(4): 894-895. PubMed 15194307

12. Ullum H, Lepri AC, Katzenstein TL, et al. Prognostic value of single measurements of beta-2-microglobulin, immunoglobulin A in HIV disease after controlling for CD4 lymphocyte counts and plasma HIV RNA levels. Scand J Inject Dis. 2000; 32(4):371-376. PubMed 10959644

13. Winchester JF, Salsberg JA, Levin NW. Beta-2 microglobulin in ESRD: an in-depth review. Adv Ren Replace Ther. 2003 Oct; 10(4):279-309. PubMed 14681859

14. Drüeke TB, Massy ZA. Beta2-microglobulin. Semin Dial. 2009 Jul-Aug; 22(4):378-380. PubMed 19708985

15. Okuno S, Ishimura E, Kohno K, et al. Serum beta2-microglobulin level is a significant predictor of mortality in maintenance haemodialysis patients. Nephrol Dial Transplant. 2009 Feb; 24(2):571-577. PubMed 18799606

16. Cheung AK, Greene T, Leypoldt JK, et al. Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2008 Jan; 3(1):69-77. PubMed 18057309

17. Cheung AK, Rocco MV, Yan G, et al. Serum beta-2 microglobulin levels predict mortality in dialysis patients: Results of the HEMO study. J Am Soc Nephrol. 2006 Feb; 17(2):546-555. PubMed 16382021

18. Kawai K, Kawashima S, Miyazaki T, et al. Serum beta2-microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients. J Cardiol. 2010 Jan; 55(1):99-107. PubMed 20122555