title: Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States.
abstract: Using laser microdissection and mass spectrometry (MS)-based proteomics, we subtyped amyloid deposits from 130 cases of hepatic amyloidosis. Although we confirmed that immunoglobulin light chain amyloidosis was the most frequent cause of hepatic amyloidosis, leukocyte cell-derived chemotaxin 2 (LECT2) amyloidosis (ALect2) accounted for 25% of cases. This novel finding was associated with Hispanic ancestry, incidental discovery of amyloid in liver specimens sampled for other unrelated conditions, and a characteristic pattern of hepatic amyloid deposition. Although ALect2 patients had a common LECT2 polymorphism, pathogenic mutations were not discovered, suggesting that constitutive or compensatory LECT2 overexpression led to ALect2 deposition. These findings indicate that ALect2 is a common cause of hepatic amyloidosis in the population of the United States, and subtyping hepatic amyloid deposits by an accurate analytic method such as MS is required for optimal clinical management of hepatic amyloidosis patients and to avoid incorrect and unnecessarily toxic therapies.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN;
authors.forename: Oana M
authors.initials: OM
authors.lastname: Mereuta
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vrana
authors.forename: Mark E
authors.initials: ME
authors.lastname: Law
authors.forename: Karen L
authors.initials: KL
authors.lastname: Grogg
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.forename: Vishal S
authors.initials: VS
authors.lastname: Chandan
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Victor H
authors.initials: VH
authors.lastname: Jimenez-Zepeda
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D013058:Mass Spectrometry; D042282:Microdissection; D008875:Middle Aged; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D014481:United States
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C103468:LECT2 protein, human