Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine

Giovanni Palladini, Paola Russo, Tiziana Bosoni, Laura Verga, Gabriele Sarais, Francesca Lavatelli, Mario Nuvolone, Laura Obici, Simona Casarini, Simona Donadei, Riccardo Albertini, Gabriella Righetti, Maddalena Marini, Maria Stella Graziani, Gian Vico Melzi D'Eril, Remigio Moratti, Giampaolo Merlini

Research output: Contribution to journalArticle

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) κ/λ 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 κ/λ 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 bi-clonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC k/A 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 κ/λ 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.

Original languageEnglish
Pages (from-to)499-504
Number of pages6
JournalClinical Chemistry
Volume55
Issue number3
DOIs
Publication statusPublished - Mar 1 2009

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Assays
Urine
Light
Serum
Amyloidosis
Agar Gel Electrophoresis
Biopsy
Amyloid Plaques
Electrophoresis
Amyloid
Sepharose
Deposits
Gels
Immunoglobulin Light Chains
Abdominal Fat
Paraproteinemias
Immunoelectron Microscopy
Statistical methods
Microscopic examination
Demonstrations

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. / Palladini, Giovanni; Russo, Paola; Bosoni, Tiziana; Verga, Laura; Sarais, Gabriele; Lavatelli, Francesca; Nuvolone, Mario; Obici, Laura; Casarini, Simona; Donadei, Simona; Albertini, Riccardo; Righetti, Gabriella; Marini, Maddalena; Graziani, Maria Stella; D'Eril, Gian Vico Melzi; Moratti, Remigio; Merlini, Giampaolo.

In: Clinical Chemistry, Vol. 55, No. 3, 01.03.2009, p. 499-504.

Research output: Contribution to journalArticle

Palladini, Giovanni ; Russo, Paola ; Bosoni, Tiziana ; Verga, Laura ; Sarais, Gabriele ; Lavatelli, Francesca ; Nuvolone, Mario ; Obici, Laura ; Casarini, Simona ; Donadei, Simona ; Albertini, Riccardo ; Righetti, Gabriella ; Marini, Maddalena ; Graziani, Maria Stella ; D'Eril, Gian Vico Melzi ; Moratti, Remigio ; Merlini, Giampaolo. / Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. In: Clinical Chemistry. 2009 ; Vol. 55, No. 3. pp. 499-504.
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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) κ/λ 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 κ/λ 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 bi-clonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC k/A 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 κ/λ 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.",
author = "Giovanni Palladini and Paola Russo and Tiziana Bosoni and Laura Verga and Gabriele Sarais and Francesca Lavatelli and Mario Nuvolone and Laura Obici and Simona Casarini and Simona Donadei and Riccardo Albertini and Gabriella Righetti and Maddalena Marini and Graziani, {Maria Stella} and D'Eril, {Gian Vico Melzi} and Remigio Moratti and Giampaolo Merlini",
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T1 - Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine

AU - Palladini, Giovanni

AU - Russo, Paola

AU - Bosoni, Tiziana

AU - Verga, Laura

AU - Sarais, Gabriele

AU - Lavatelli, Francesca

AU - Nuvolone, Mario

AU - Obici, Laura

AU - Casarini, Simona

AU - Donadei, Simona

AU - Albertini, Riccardo

AU - Righetti, Gabriella

AU - Marini, Maddalena

AU - Graziani, Maria Stella

AU - D'Eril, Gian Vico Melzi

AU - Moratti, Remigio

AU - Merlini, Giampaolo

PY - 2009/3/1

Y1 - 2009/3/1

N2 - 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) κ/λ 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 κ/λ 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 bi-clonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC k/A 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 κ/λ 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.

AB - 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) κ/λ 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 κ/λ 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 bi-clonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC k/A 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 κ/λ 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.

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