Beta 2 microglobulin

• Beta-2 microglobulin (B2m) is the 11.8 kDa light-chain moiety of major histocompatibility complex class I (MHC I) present on the surface of nearly all nucleated cells
  • MHC I functions immunologically in antigen presentation to cytotoxic T cells
    • MHC I complex has also been implicated in nonimmunologic functions associated with hormone/growth factor (EGF, insulin, IGF-I, IGF-II) receptor interactions and cellular proliferation
    • MHC I are present on almost all cells (a significant exception is red blood cells)
  • circulating B2m
    • B2m is elevated in several lymphoproliferative disorders including chronic lymphocytic leukemia, lymphomas, and multiple myeloma
      • prognostic power of B2m with regard to overall survival has also been shown for B-cell malignancies such as diffuse large cell and follicular lymphoma and , multiple myeloma, chronic lymphocytic leukaemia and acute lymphoblastic leukaemia (1)
      • B2M level at the time of diagnosis to be an independent prognostic parameter for survival and for the risk of developing acute myeloid leukaemia in high-risk myelodysplastic syndrome patients (2)
    • elevation in tissue/serum levels of B2m in solid malignancies such as breast, lung, gastrointestinal, and nasopharyngeal carcinomas has also been reported
    • B2m levels also rise during infection with some viruses, including cytomegalovirus and human immunodeficiency virus (HIV). Studies show that as HIV disease advances, beta2-microglobulin levels increase
    • serum levels may also be increased due to increased production in hepatitis, sarcoidosis, Crohn's disease and vasculitis
  • urinary levels are increased in tubular damage
    • possible causes of raised urinary levels include:
      • heavy-metal poisoning e.g. mercury, cadmium, cis-platinum
      • drug toxicity e.g. aminoglycosides, cyclosporin
      • hereditary e.g. Fanconi's syndrome, Wilson's disease, cystinosis
      • pyelonephritis
      • renal allograft rejection
      • others e.g. nephrocalcinosis

Notes:

• if renal disease is suspected, comparing serum and urine B2m levels helps identify the site of renal damage
  • B2m normally is filtered by the renal glomeruli, only to be partially reabsorbed back into the blood when it reaches the renal tubules
    • in glomerular disease, the glomeruli cannot filter it out of the blood, so serum levels increase and B2m levels decrease in the urine
    • in tubular disease, the tubules cannot reabsorb it back into the blood, so urine levels rise and serum levels fall
      • after a kidney transplant, increased serum levels may be an early sign of rejection

Reference:

• 1) Gatto S et al. Contribution of beta-2 microglobulin levels to the prognostic stratification of survival in patients with myelodysplastic syndrome (MDS). Blood 2003;102:1622-1625.
• 2) Neumann F et al. Levels of beta 2 microglobulin have a prognostic relevance for patients with myelodysplastic syndrome with regard to survival and the risk of transformation into acute myelogenous leukemia Leukemia Research 2009; 33(2): 232-236
• 3) Rowley RD et al. beta-2 Microglobulin is mitogenic to PC-3 prostatic carcinoma cells and antagonistic to transforming growth factor beta 1 action. Cancer Res (1995);55:781-786.
• 4) Jacobs EL, Haskell CM. Clinical use of tumor markers in oncology. Curr Prob Cancer 1991;15: 301-320.