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

Roshini S. Abraham, Susan M. Geyer, Tammy L. Price-Troska, Cristine Allmer, Robert A. Kyle, Morie Gertz, Rafael Fonseca

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

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 germline genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germline 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 germline 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.

Original languageEnglish (US)
Pages (from-to)3801-3808
Number of pages8
JournalBlood
Volume101
Issue number10
DOIs
StatePublished - May 15 2003

Fingerprint

Immunoglobulin Light Chains
Amyloidosis
Genes
Light
Amyloid
Immunoglobulin Light Chain Genes
Kidney
Paraproteinemias
Survival
Amyloid Plaques
Multiple Myeloma
B-Lymphocytes
Tissue Donors
Deposits
Cells
Tissue
Plasmas

ASJC Scopus subject areas

  • Hematology

Cite this

Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). / Abraham, Roshini S.; Geyer, Susan M.; Price-Troska, Tammy L.; Allmer, Cristine; Kyle, Robert A.; Gertz, Morie; Fonseca, Rafael.

In: Blood, Vol. 101, No. 10, 15.05.2003, p. 3801-3808.

Research output: Contribution to journalArticle

Abraham, Roshini S. ; Geyer, Susan M. ; Price-Troska, Tammy L. ; Allmer, Cristine ; Kyle, Robert A. ; Gertz, Morie ; Fonseca, Rafael. / Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). In: Blood. 2003 ; Vol. 101, No. 10. pp. 3801-3808.
@article{4cb62a0c416e4b9882308195d0d3eddc,
title = "Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL)",
abstract = "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 germline genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germline 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 germline 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.",
author = "Abraham, {Roshini S.} and Geyer, {Susan M.} and Price-Troska, {Tammy L.} and Cristine Allmer and Kyle, {Robert A.} and Morie Gertz and Rafael Fonseca",
year = "2003",
month = "5",
day = "15",
doi = "10.1182/blood-2002-09-2707",
language = "English (US)",
volume = "101",
pages = "3801--3808",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL)

AU - Abraham, Roshini S.

AU - Geyer, Susan M.

AU - Price-Troska, Tammy L.

AU - Allmer, Cristine

AU - Kyle, Robert A.

AU - Gertz, Morie

AU - Fonseca, Rafael

PY - 2003/5/15

Y1 - 2003/5/15

N2 - 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 germline genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germline 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 germline 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.

AB - 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 germline genes was noted for both AL κ and λ patients. There was a significant correlation between the use of the Vλ VI germline 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 germline 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.

UR - http://www.scopus.com/inward/record.url?scp=0038264427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038264427&partnerID=8YFLogxK

U2 - 10.1182/blood-2002-09-2707

DO - 10.1182/blood-2002-09-2707

M3 - Article

C2 - 12515719

AN - SCOPUS:0038264427

VL - 101

SP - 3801

EP - 3808

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -