Beta 2‐microglobulin (β2‐M) was discovered in 1968 by Berggård et al. in the urine of patients with Wilson's disease and in patients with chronic cadmium poisoning. β2‐M is a small globular peptide with a molecular weight of 11800 Da. It is identical to the light chain of the major histocompatibility complex (MHC) antigen (HLA) 5. Its tertiary structure is homologous to the CH3‐IgG immunoglobulin domain. Thus β2‐M is expressed on the extraplasma surface of nearly all nucleated cells (exception: trophoblasts). β2‐M consists of 100 amino acids with a disulfide- linked loop between amino acid 25 and 81. β2‐M is non-covalently associated with the class 1 MHC antigen, and is identical to BDGF (bone- derived growth factor 2), CRG‐8, and thymotaxin. β2‐M is normally cleared exclusively by the kidneys. It passes freely through the glomerular membrane, and then is reabsorbed to an amount of up to 99.9 % by the proximal tubules. Changes in serum β-2 microglobulin levels or β-2 microglobulin excretion are caused by an increase in production, a change in glomerular filtration rate (GFR) or tubular reabsorption.
It has been published that elevated serum levels of β2‐M occur in renal diseases such as glomerulopathies, tubulopathies, renal failure, and amyloidosis. In addition, it has been reported that other increased serum levels are found in rheumatoid arthritis and autoimmune diseases.
Since the lymphatic system is the main synthesis site of β-2 microglobulin, all conditions with an increased proliferation rate of lymphocytic cells are associated with elevated serum concentrations e.g. multiple myelomas, Hodgkin's lymphomas, chronic lymphocytic leukemias and other malignant non-Hodgkin's lymphomas.
In healthy people, β-2 microglobulin is synthesised at a relatively constant rate and released into the body fluids during the process of natural cell regeneration, it is subject to free glomerular filtration and tubular reabsorption. A reduction in GFR prolongs the half-life of β-2 microglobulin and serum concentrations increase exponentially. Excretion of β-2 microglobulin is increased in the case of tubular damage e.g. due to bacterially induced interstitial nephritis and cadmium nephropathy. β-2 microglobulin is frequently used to test renal tubular function, particularly in kidney transplant patients in whom rejection of the allograft will manifest as an increase in serum β-2 microglobulin due to tubulopathy.