title: Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine.
abstract: BACKGROUND
  The diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis requires demonstration of amyloid deposits in a tissue biopsy and amyloidogenic monoclonal light chains. The optimal strategy to identify the amyloidogenic clone has not been established. We prospectively assessed the diagnostic sensitivity of the serum free light chain (FLC) kappa/lambda ratio, a commercial serum and urine agarose gel electrophoresis immunofixation (IFE), and the high-resolution agarose gel electrophoresis immunofixation (HR-IFE) developed at our referral center in patients with AL amyloidosis, in whom the amyloidogenic light chain was unequivocally identified in the amyloid deposits.
  
  
  METHODS
  The amyloidogenic light chain was identified in 121 consecutive patients with AL amyloidosis by immunoelectron microscopy analysis of abdominal fat aspirates and/or organ biopsies. We characterized the monoclonal light chain by using IFE and HR-IFE in serum and urine and the FLC kappa/lambda ratio in serum. We then compared the diagnostic sensitivities of the 3 assays.
  
  
  RESULTS
  The HR-IFE of serum and urine identified the amyloidogenic light chain in all 115 patients with a monoclonal gammopathy. Six patients with a biclonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC kappa/lambda ratio (96% vs 76%). The combination of serum IFE and the FLC assay detected the amyloidogenic light chain in 96% of patients. The combination of IFE of both serum and urine with the FLC kappa/lambda ratio had a 100% sensitivity.
  
  
  CONCLUSIONS
  The identification of amyloidogenic light chains cannot rely on a single test and requires the combination of a commercially available FLC assay with immunofixation of both serum and urine.
authors.affiliation: Center for Amyloidosis, Biotechnology Research Laboratories, Department of Biochemistry, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.forename: Paola
authors.initials: P
authors.lastname: Russo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bosoni
authors.forename: Laura
authors.initials: L
authors.lastname: Verga
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sarais
authors.forename: Francesca
authors.initials: F
authors.lastname: Lavatelli
authors.forename: Mario
authors.initials: M
authors.lastname: Nuvolone
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.forename: Simona
authors.initials: S
authors.lastname: Casarini
authors.forename: Simona
authors.initials: S
authors.lastname: Donadei
authors.forename: Riccardo
authors.initials: R
authors.lastname: Albertini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Righetti
authors.forename: Maddalena
authors.initials: M
authors.lastname: Marini
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Graziani
authors.forename: Gian Vico
authors.initials: GV
authors.lastname: Melzi D'Eril
authors.forename: Remigio
authors.initials: R
authors.lastname: Moratti
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
mesh_terms: D000686:Amyloidosis / Q000097:blood* / Q000276:immunology / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000276:immunology / Q000652:urine*; D008297:Male
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains