Polymerization of intact β₂-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis

Systemic amyloidosis with a prediction for bone and synovium may complicate the course of patients on long-term hemodialysis. This form of amyloidosis can be typed as distinct from other amyloid diseases by using small tissue samples obtained by bone biopsy and at postmortem. Immunoblot analysis of two-dimensional gels of partially solubilized amyloid fibrils established that tissue deposits are composed of monomer, dimers, and higher polymers of β₂-microglobulin (β₂m) and that amyloid P component was also present. Anti-β₂m antiserum recognized fibrils, as shown by immunoelectron microscopy. Purified monomer isolated from dissociated fibrils yielded peptides corresponding to the entire known sequence of β₂m. Virtually all serum β₂m, as well as that present in tissue fluid bathing amyloid fibrils, was monomeric. Hemodialysis-related amyloidosis is an example of a deposition disease occurring in hemodialysis patients. We have shown conclusively that, in this amyloid disease, polymerization of an intact normal serum protein to a fibrillar configuration may occur without proteolysis. We propose the designation Aβ₂m for this form of amyloid fibril subunit protein.