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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
111
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.