Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

51-POS Board 26 Urinary Exosomes Allow for the Identification of Pathogenic Light Chains in Light Chain Amyloidosis Tissues Marina Ramirez-Alvarado 1 , David R. Barnidge 1 , Angela Dispenzieri 1 , Marin-Argany Marta 1 , Dick J. Christopher 1 , Nasr Samih 1 , Leung Nelson 1 . 1 Mayo Clinic, Rochester, MN, USA, 2 Mayo Clinic, Rochester, MN, USA, 3 Mayo Clinic, Rochester, MN, USA. Immunoglobulin light chain (AL) amyloidosis is a potential fatal complication of B-cell clonal proliferation. Currently, the best biomarker for treatment monitoring is serum free light chain (FLC) assay but it cannot distinguish monoclonal FLC from polyclonal FLC once it drops below the lower limit of normal for FLC. Urinary EXs have previously been found to display different characteristics among patients with AL amyloidosis compared to controls. High molecular weight LC oligomers are found only in patients with active AL amyloidosis (1). We hypothesize that urinary EXs can be used as a biomarker to assess organ response in cases where the patient had reached hematologic complete response (CR) but continue to exhibit organ progression. Exosomes were extracted and fractionated as previously reported (1). Intact immunoglobulin light chains were identified in patient plasma, EX, and kidney biopsy amyloid deposits using mass spectrometry as the detection method (2). Oligomeric LCs species were only found in urinary EXs of patient AL-ex11 (progressive renal failure). New patient AL-ex12 urinary EXs do not present oligomeric LC species. AL-ex13 and AL-ex14 were in hematologic and organ CR and their EXs did not present any oligomeric species. The monoclonal LC in AL-ex11 urinary EXs at the time of hematologic CR was identified as a lambda 6a (IGLV 6-57). The LC found in the urinary exosomes has the same molecular mass and sequence of the protein found in the kidney amyloid biopsy and the cDNA from the plasma cell clone. The urinary EXs enrich the pathogenic protein and allowed for the identification of the pathogenic FLC protein by mass spectrometry and cDNA sequencing. 1. Ramirez-Alvarado M, et al. PloS one. 2012;7(6):e38061. 2. Botz CM, et al. British journal of haematology. 2014;167(3):437-8.

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