Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain–associated amyloidosis (AL)

Light chain–associated amyloidosis (AL) is a plasma cell dyscrasia in which the secreted monoclonal immunoglobulin (Ig) light chains form amyloid fibrils. There is considerable heterogeneity in clinical presentation, and prognosis of the disease relates to the severity of organ dysfunction induced b...

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Bibliographic Details
Published in:Blood 2003-05, Vol.101 (10), p.3801-3808
Main Authors: Abraham, Roshini S., Geyer, Susan M., Price-Troska, Tammy L., Allmer, Cristine, Kyle, Robert A., Gertz, Morie A., Fonseca, Rafael
Format: Article
Language:English
Subjects:
Amyloidosis
Amyloidosis, Familial - classification
Amyloidosis, Familial - genetics
Amyloidosis, Familial - immunology
Biological and medical sciences
Databases, Factual
Female
Genes, Immunoglobulin
Humans
Immunoglobulin Light Chains - genetics
Immunoglobulin Variable Region - genetics
Male
Medical sciences
Metabolic diseases
Other metabolic disorders
Patient Selection
Retrospective Studies
Syndrome
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Summary:Light chain–associated amyloidosis (AL) is a plasma cell dyscrasia in which the secreted monoclonal immunoglobulin (Ig) light chains form amyloid fibrils. There is considerable heterogeneity in clinical presentation, and prognosis of the disease relates to the severity of organ dysfunction induced by amyloid deposits. The mechanisms by which the amyloid fibrils are deposited as well as the predilection for specific organ sites have not been clearly elucidated. This study characterizes the repertoire of immunoglobulin light chain variable genes used by the clonal B cell in AL amyloid patients, and the association of light chain variable region (VL) genes with clinical presentation and outcome is assessed in 58 (32 λ and 26 κ) patients. A preferential use of VL germ-line genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germ-line donor, 6a, and renal involvement as well as the Vλ III gene, 3r, with soft-tissue AL. The use of a biased VL gene repertoire also correlated with clinical outcome, revealing important trends for predicting prognosis. The use of Vλ II germ-line genes was associated with cardiac amyloidosis and affected survival adversely. The presence of multiple myeloma also correlated with a poor prognosis. The presence of renal disease, on the other hand, was associated with improved survival. Therefore, identification of the clonal VL gene in AL has important implications in determining clinical outcome.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2002-09-2707