Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine.
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.
Palladini
Giovanni
G
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.
Russo
Paola
P
Bosoni
Tiziana
T
Verga
Laura
L
Sarais
Gabriele
G
Lavatelli
Francesca
F
Nuvolone
Mario
M
Obici
Laura
L
Casarini
Simona
S
Donadei
Simona
S
Albertini
Riccardo
R
Righetti
Gabriella
G
Marini
Maddalena
M
Graziani
Maria Stella
MS
Melzi D'Eril
Gian Vico
GV
Moratti
Remigio
R
Merlini
Giampaolo
G
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
D015415:Biomarkers; D007147:Immunoglobulin Light Chains