Identification of Amyloidogenic Light Chains

Dátum: 02.10.2010 09:22
Vec: Mnohopocetný myelóm

Identification of Amyloidogenic Light Chains Requires the Combination of Serum-Free Light Chain Assay with Immunofixation of Serum and Urine

Giovanni Palladini,1 Paola Russo,1,2 Tiziana Bosoni,3 Laura Verga,1,4 Gabriele Sarais,1 Francesca Lavatelli,1,2 Mario Nuvolone,1,2 Laura Obici,1 Simona Casarini,1 Simona Donadei,1 Riccardo Albertini,3 Gabriella Righetti,5 Maddalena Marini,5 Maria Stella Graziani,5 Gian Vico Melzi D’Eril,6 Remigio Moratti,3 and Giampaolo Merlini1*
1 Center for Amyloidosis, Biotechnology Research Laboratories, Department of Biochemistry;
2 Department of Internal Medicine;
3 Clinical Chemistry Laboratory;
4 Department of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo and University of Pavia, Pavia, Italy;
5 Clinical Chemistry Laboratory, Ospedale Civile Maggiore, Verona, Italy;
6 Department of Medicine and Surgery, University of Milan, Milan, Italy.

* Address correspondence to this author at: Amyloid Center, Biotechnology Research Laboratories—Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi, 19-27100 Pavia, Italy. Fax 39-0382-502990; e-mail

Clinical Chemistry 55:3 499–504 (2009)

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) k/l 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 k/l 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 k/l 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 k/l 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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