title: Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry.
abstract: The goal of this study was to investigate the frequency of use of light-chain variable region (IGVL) genes among patients with systemic (ALS) and localized (ALL) amyloidosis and to assess for associations between IGVL gene usage and organ tropism. We evaluated clinic charts from 821 AL patients seen at the Mayo Clinic who had bone marrow, fat pad, and solid organ tissue samples typed by liquid chromatography tandem mass spectrometry (LC-MS). We identified 701 patients with ALSand 120 with ALLOverall, we were able to identify an IGVL gene in 87 (72%) patients with ALLand 573 (82%) patients with ALSWhen compared with ALL, LV6-57 was more common, whereas KV3-20 and heavy-chain codeposition were less common in ALSIn this large series of ALS, characteristics particular to specific genotypes became apparent. LV6-57 patients were more likely to have renal involvement and to harbor a translocation 11;14. LV3-01 patients were less likely to have advanced cardiac disease and renal involvement. LV2-14 patients were more likely to have peripheral nerve involvement, an intact circulating immunoglobulin, and lower circulating dFLC. LV1-44 patients were more likely to have cardiac involvement. KV1-33 patients had more liver involvement and higher circulating dFLC. Finally, KV1-05 was associated with inferior overall survival but not independently of cardiac stage. IGVL gene usage appears to provide clues about disease pathophysiology and tissue tropism. LC-MS is a high-throughput and low-resource technique that can be used to identify IGVL gene from clinical tissue specimens.
authors.affiliation: Division of Hematology, Department of Medicine.
authors.forename: Taxiarchis V
authors.initials: TV
authors.lastname: Kourelis
authors.affiliation: Department of Health Sciences Research.
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Department of Laboratory Medicine and Pathology.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.affiliation: Department of Biochemistry and Molecular Biology, and.
authors.forename: Marina
authors.initials: M
authors.lastname: Ramirez-Alvarado
authors.affiliation: Department of Laboratory Medicine and Pathology.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.affiliation: Division of Hematology, Department of Medicine.
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.affiliation: Division of Hematology, Department of Medicine.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeldenrust
authors.affiliation: Division of information Management and Analytics, Mayo Clinic, Rochester, MN; and.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Zenka
authors.affiliation: Department of Laboratory Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.affiliation: Division of Hematology, Department of Medicine.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
mesh_terms: D000686:Amyloidosis / Q000150:complications / Q000235:genetics*; D005803:Genes, Immunoglobulin; D006331:Heart Diseases; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region; D007674:Kidney Diseases; D053719:Tandem Mass Spectrometry
chemical_list: D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region