Beta-2-microglobulin (B2M) amyloid fibrils (B2M amyloid)

Beta-2-microglobulin (β2M) amyloid fibrils are the pathological protein aggregates responsible for dialysis-related amyloidosis (DRA), a condition primarily affecting patients with end-stage renal disease (PubMed: 28213270). Under normal conditions, β2M is a small 11.8 kDa protein that serves as the light chain for the Major Histocompatibility Complex (MHC) class I and is cleared by the kidneys (UniProt: P61769). In patients with renal failure, β2M accumulates in the plasma, eventually dissociating from the MHC complex and aggregating into insoluble amyloid fibrils that deposit in the musculoskeletal system, including joints and bones (PubMed: 30135140). These deposits lead to clinical manifestations such as carpal tunnel syndrome and destructive spondyloarthropathy. Current treatments focus on reducing the systemic load of β2M through advanced dialysis techniques or adsorbent columns like Lixelle (PubMed: 15506314). Experimental therapies are investigating small molecules, such as doxycycline and EGCG, which aim to stabilize the native monomeric state or disrupt the fibrillar structure to prevent further tissue damage (PubMed: 25100787).

Other names

β2-microglobulin fibrilsB2M fibrilsDialysis-related amyloidAB2M amyloidBeta-2-microglobulin aggregates

Therapeutic strategies involve the removal of the precursor protein from the blood via adsorption or high-flux filtration, as well as the experimental use of small molecules to inhibit the conversion of monomeric beta-2-microglobulin into insoluble amyloid fibrils.