title: Assessment of renal response with urinary exosomes in patients with AL amyloidosis: A proof of concept.
abstract: Immunoglobulin light chain (AL) amyloidosis is a fatal complication of B-cell proliferation secondary to deposition of amyloid fibrils in various organs. Urinary exosomes (UEX) are the smallest of the microvesicles excreted in the urine. Previously, we found UEX of patients with AL amyloidosis contained immunoglobulin light chain (LC) oligomers that patients with multiple myeloma did not have. To further explore the role of the LC oligomers, UEX was isolated from an AL amyloidosis patient with progressive renal disease despite achieving a complete response. LC oligomers were identified. Mass spectrometry (MS) of the UEX and serum identified two monoclonal lambda LCs. Proteomics of the trypsin digested amyloid fragments in the kidney by laser microdissection and MS analysis identified a λ6 LC. The cDNA from plasma cell clone was from the IGLV- 6-57 family and it matched the amino acid sequences of the amyloid peptides. The predicted mass of the peptide product of the cDNA matched the mass of one of the two LCs identified in the UEX and serum. UEX combined with MS were able to identify 2 monoclonal lambda LCs that current clinical methods could not. It also identified the amyloidogenic LC which holds potential for response assessment in the future.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, MN, 55905, USA.|Department of Immunology, Mayo Clinic, MN, 55905, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Ramirez-Alvarado
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, 55905, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Barnidge
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, 55905, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Murray
authors.affiliation: Division of Hematology, Mayo Clinic, MN, 55905, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, MN, 55905, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Marin-Argany
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, MN, 55905, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Dick
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, MN, 55905, USA.
authors.forename: Shawna A
authors.initials: SA
authors.lastname: Cooper
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, 55905, USA.
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.affiliation: The University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ward
authors.affiliation: Health Sciences Research, Biomedical Statistics and Informatics, Mayo Clinic, MN, 55905, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Jiménez-Zepeda
authors.affiliation: Division of Hematology, Mayo Clinic, MN, 55905, USA.|Division of Nephrology and Hypertension, Mayo Clinic, MN, 55905, USA.
authors.forename: Nelson
authors.identifier: http://orcid.org/0000-0002-5651-1411
authors.initials: N
authors.lastname: Leung
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D000075363:Immunoglobulin Light-chain Amyloidosis; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008970:Molecular Weight; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000652:urine; D011507:Proteinuria / Q000175:diagnosis* / Q000209:etiology*; D017422:Sequence Analysis, DNA
chemical_list: D007147:Immunoglobulin Light Chains; D066329:Protein Aggregates