b2 Microglobulin

Clinical use:
Renal function
: In proximal tubular dysfunction a large excess of b2microglobulin is excreted in the urine and thus increased urine concentrations occur. Grossly raised urine b2 microglobulin concentrations are seen in heavy metal, aminoglycoside or cytoxic induced renal tubular damage. Urinary pH of <6.0 is known to degrade b2 microglobulin in the bladder, therefore the measurement of urinary concentrations of this protein is of limited value.
For the diagnosis and management of renal tubular disorders the estimation of a 1 microglobulin or retinol-binding protein is to be preferred because of the inherent instability of b2 microglobulin at low pH.

Urinary tract malformations: Raised serum b2 microglobulin concentrations have been described in association with fetal urinary tract malformations at 16 – 17 weeks gestation. Fetal blood samples collected at cordocentesis show b2 microglobulin concentrations above 5.6 mg/L in renal agenesis and in multicystic dysplasia.

Renal transplantation: Serum b2 microglobulin may decrease during chemotherapy or corticosteroid therapy due to depression of synthesis and it may be increased by the stimulation of the lymphoid system by allograft rejection. The measurement of b2 microglobulin, especially in serum, has to be viewed with care; daily determinations of serum and urine concentrations can improve the immunological monitoring of the transplant. The decrease of serum b2 microglobulin during the early post-operative days indicates a viable transplant whereas a rise in serum concentration is one of the earliest manifestations of acute rejection. A rise in the serum concentration after the first month may be associated with viral infection with or without rejection.

Elevation of urinary b2 microglobulin excretion indicates tubular dysfunction which is usually the manifestation of tubular interstitial rejection. a 1microglobulin or retinol-binding protein can be used in this context also and prove more reliable.

Malignancy: In general serum concentrations of b2 microglobulin are raised in cancer, but in most cases the concentration is non-specific with respect to tumour type, severity of disease or time, and again in many cases the concentration overlaps with the normal range. Some rare tumours such as choriocarcinoma or teratoma show no increase in b2 microglobulin despite widespread disease. There are no clinical applications or benefits in the measurements of b2 microglobulin in chronic lymphocytic leukaemia, Hodgkins disease, non-Hodgkins lymphoma or Burkitt’s tumour although there is some evidence that serum and CSF measurements in patients with acute leukaemia may give information on the CNS involvement.

Multiple Myeloma: High cell turnover in myeloma results in raised serum concentrations of b2 microglobulin and renal dysfunction will result in serum retention contributing further to raised concentrations. Measurement of serum b2 microglobulin indirectly reflects tumour mass, growth rate, and renal function, and, not surprisingly therefore, it is the most powerful single prognostic indicator in the management of myelomatosis. Serum concentrations below 4 mg/L at presentation indicate the best prognosis, while concentrations above 20 mg/L represent the worst prognosis. The relationship of serum b2 microglobulin to tumour mass allows this marker to be used in the same way as the serum paraprotein to monitor disease, particularily in the BJ myeloma where a serum paraprotein is absent and urinary BJ quantitation is unreliable.

a -interferon – used in the maintainence therapy of multiple myeloma – can induce a marked increase in serum b2 microglobulin concentrations and this should be taken into consideration when using b2 microglobulin for the assessment of tumour response during a -interferon therapy.

Collagen-vascular disorders: Two factors which may affect b2 microglobulin production in vivo are corticosteroid treatment and immunosuppressive chemotherapy. It has been shown that corticosteroid treatment results in a fall in b2 microglobulin concentrations in Sjogren’s syndrome, sarcoidosis, rheumatoid arthritis, and chronic hepatitis. The disease states themselves, however, result in an increase in the b2 microglobulin concentration. In Sjogren’s syndrome the decrease can be demonstrated in serum and saliva while in rheumatoid arthritis increased concentrations are found in joint and synovial fluids as well as in serum.

AIDS and AIDS related complex: Serum b2 microglobulin concentrations are an accurate predictor of disease progression in all risk groups, including haemophiliacs. Levels in excess of 5 mg/L at presentation are associated with rapid progression and poor prognosis.

Sample requirement: 2 mL serum or relevant body fluid.

The estimation of this protein in urine is not recommended due to its inherent instability at acid pH.

Reference range:

Adult reference range only; no data is available for concentrations in childhood.

Foetal serum 2.3 – 4.7 mg/L
Serum 1.2 – 2.4 mg/L
CSF 0.1 – 2.8 mg/L *

* Reference concentrations for CSF are derived from patients with normal renal function and showing no evidence of malignancy.

Centres offering this assay: 
Cardiff UHW PRU Diagnostic Service
London St George’s Hospital PRU Diagnostic Service
Sheffield Northern General’s PRU Diagnostic Service

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