What causes beta-2-microglobulin (beta-2m) amyloidosis?

Updated: Nov 14, 2019
  • Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Beta-2m is a glycosylated polypeptide with a molecular weight of 11,800 dalton. It makes up the beta chain of the human leukocyte antigen (HLA) class I molecule and has the prominent beta-pleated structure that is characteristic of amyloid fibrils.

Beta-2m is present on the surface of most nucleated cells and in most biologic fluids, including urine and synovial fluid. It circulates as an unbound monomer distributed in the extracellular space and polymerizes to form amyloid deposits in a variety of tissues. Capillary electrophoresis recognizes 2 or 3 conformational isomers of beta-2m in human serum. [5]

In the normally functioning kidney, beta-2m is cleared by glomerular filtration and is catabolized in the proximal tubules. Reference range serum levels are 1.5-3 mg/L. In renal failure, impaired renal catabolism causes an increase in synthesis and release of beta-2m, and levels can rise 10- to 60-fold. Retention and accumulation of this type of amyloid protein is presumed to be the main pathogenic process underlying beta-2m amyloidosis.

There is also some suggestion that the dialysis process itself may stimulate beta-2m synthesis, by activation of complements and cytokine production. However, this is probably not a significant mechanism of dialysis-related amyloidosis (DRA), since the disease is also seen in patients on CAPD and people who have never been on dialysis.


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