Abstract | BACKGROUND: METHODS AND FINDINGS: We have developed a sensitive binding assay quantifying the recruitment of full length, patient-derived LC proteins by synthetic amyloid fibrils, as a method for studying their amyloidogenic potential. In a survey of eight urinary LC, both AL and MM-associated proteins were recruited by synthetic amyloid fibrils; however, AL-associated LC bound significantly more efficiently (p < 0.05) than did MM LCs. The LC proteins used in this study were isolated from urine and presumed to represent a surrogate of serum free light chains. CONCLUSION: The binding of LC to synthetic fibrils in this assay accurately differentiated LC with amyloidogenic propensity from MM LC that were not associated with clinical amyloid disease. Notably, the LC from a MM patient who subsequently developed amyloid behaved as an AL-associated protein in the assay, indicating the possibility for identifying MM patients at risk for developing amyloidosis based on the light chain recruitment efficacy. With this information, at risk patients can be monitored more closely for the development of amyloidosis, allowing timely administration of novel, amyloid-directed immunotherapies-this approach may improve the prognosis for these patients.
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Authors | Emily B Martin, Angela Williams, Craig Wooliver, R Eric Heidel, Sarah Adams, John Dunlap, Marina Ramirez-Alvarado, Luis M Blancas-Mejia, Ronald H Lands, Stephen J Kennel, Jonathan S Wall |
Journal | PloS one
(PLoS One)
Vol. 12
Issue 3
Pg. e0174152
( 2017)
ISSN: 1932-6203 [Electronic] United States |
PMID | 28350808
(Publication Type: Journal Article)
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Chemical References |
- Amyloid
- Amyloidogenic Proteins
- Immunoglobulin Light Chains
- Urea
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Amyloid
(immunology, metabolism, ultrastructure)
- Amyloidogenic Proteins
(immunology, metabolism)
- Amyloidosis
(immunology, metabolism)
- Blotting, Western
- Electrophoresis, Polyacrylamide Gel
- Female
- Humans
- Immunoglobulin Light Chains
(chemistry, immunology, metabolism)
- Immunoglobulin Light-chain Amyloidosis
- Male
- Microscopy, Immunoelectron
- Middle Aged
- Multiple Myeloma
(immunology, metabolism)
- Prognosis
- Protein Binding
- Protein Multimerization
(drug effects)
- Surface Plasmon Resonance
- Thermodynamics
- Urea
(pharmacology)
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