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Polymerization of intact beta 2-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis
Abstract:
Systemic amyloidosis with a predilection 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 monomers, dimers, and higher polymers of beta 2-microglobulin (beta 2m) and that amyloid P component was also present. Anti-beta 2m antiserum recognized fibrils, as shown by immunoelectron microscopy. Purified monomer isolated from dissociated fibrils yielded peptides corresponding to the entire known sequence of beta 2m. Virtually all serum beta 2m, 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 A beta 2m for this form of amyloid fibril subunit protein.
Insights
Systemic amyloidosis in hemodialysis patients involves beta 2-microglobulin (beta 2m) polymerization. This condition, termed A beta 2m amyloidosis, occurs without protein breakdown, affecting bone and synovium.
Area of Science:
- Biochemistry
- Pathology
- Nephrology
Background:
- Systemic amyloidosis can affect patients undergoing long-term hemodialysis.
- This amyloidosis shows a specific affinity for bone and synovial tissues.
- It is distinguishable from other amyloid diseases through tissue analysis.
Purpose of the Study:
- To characterize the protein composition of amyloid deposits in hemodialysis patients.
- To elucidate the mechanism of amyloid fibril formation in this specific patient group.
- To propose a designation for this amyloidosis.
Main Methods:
- Immunoblot analysis of amyloid fibrils from tissue samples.
- Two-dimensional gel electrophoresis to analyze protein components.
- Immunoelectron microscopy using anti-beta 2m antiserum.
- Peptide analysis of purified monomers.
Main Results:
- Amyloid deposits consist of beta 2-microglobulin (beta 2m) in monomeric, dimeric, and polymeric forms, along with amyloid P component.
- Anti-beta 2m antibodies recognized the amyloid fibrils.
- Purified beta 2m monomers from fibrils matched the known protein sequence.
- Serum and tissue fluid beta 2m were predominantly monomeric.
Conclusions:
- Hemodialysis-related amyloidosis involves the polymerization of intact beta 2-microglobulin (beta 2m).
- This polymerization occurs without proteolysis, differentiating it from other amyloidosis types.
- The proposed designation for this amyloid fibril subunit protein is A beta 2m.