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A monoclonal antibody recognizing apolipoprotein E peptides in systemic amyloid deposits
T Yamada1, T Kakihara, F Gejyo
1Department of Laboratory Medicine, Niigata University School of Medicine, Japan.
Annals of Clinical and Laboratory Science
|May 1, 1994
Summary
Researchers developed a new antibody (YK-2) that identifies amyloid deposits in systemic amyloidosis. This antibody targets apolipoprotein E fragments, suggesting a common marker for various amyloidosis types.
Area of Science:
- Immunology and Pathology
- Biochemistry of Amyloidosis
Background:
- Systemic amyloidosis is characterized by the deposition of misfolded proteins, forming amyloid fibrils.
- Current diagnostic methods for amyloidosis can be invasive and lack specificity for fibril composition.
- Amyloid A (AA) amyloidosis is a significant subtype, but common markers for diverse amyloid types are needed.
Purpose of the Study:
- To develop and characterize a novel monoclonal antibody for detecting amyloid deposits.
- To investigate the antigenic components of amyloid fibrils from various systemic amyloidosis subtypes.
- To identify potential common markers for immunohistochemical diagnosis of systemic amyloidosis.
Main Methods:
- Production of a monoclonal antibody (YK-2) by immunizing mice with crude amyloid A (AA) fibril preparations.
- Immunohistochemical staining of amyloid deposits in diverse patient tissue samples.
- Immunoblotting analysis of AA fibrils and normal human serum components.
- Absorption studies using purified human apolipoprotein E to identify antibody targets.
Main Results:
- The YK-2 antibody demonstrated positive staining in amyloid deposits across multiple systemic amyloidosis types (idiopathic, myeloma-associated, reactive, familial, dialysis-associated).
- Immunoblotting showed YK-2 reactivity with specific molecular weight components (14,000 and 7,000 Da) of AA fibrils and a 36,000 Da component in normal serum.
- Antibody staining was abolished by absorption with apolipoprotein E, indicating its target.
Conclusions:
- Fragments of apolipoprotein E are common constituents of amyloid fibrils, regardless of their origin.
- The YK-2 monoclonal antibody, targeting apolipoprotein E fragments, serves as a potential new immunohistochemical marker for systemic amyloidosis.
- This finding facilitates improved diagnostic accuracy and understanding of the molecular basis of diverse amyloidosis forms.