Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

Taxiarchis Kourelis, Surendra Dasari, Jason D. Theis, Marina Ramirez-Alvarado, Paul J. Kurtin, Morie Gertz, Steven R. Zeldenrust, Roman M. Zenka, Ahmet Dogan, Angela Dispenzieri

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The goal of this study was to investigate the frequency of use of light-chain variable region (IGVL) genes among patients with systemic (ALS) and localized (ALL) amyloidosis and to assess for associations between IGVL gene usage and organ tropism. We evaluated clinic charts from 821 AL patients seen at the Mayo Clinic who had bone marrow, fat pad, and solid organ tissue samples typed by liquid chromatography tandem mass spectrometry (LC-MS). We identified 701 patients with ALS and 120 with ALL. Overall, we were able to identify an IGVL gene in 87 (72%) patients with ALL and 573 (82%) patients with ALS. When compared with ALL, LV6-57 was more common, whereas KV3-20 and heavy-chain codeposition were less common in ALS. In this large series of ALS, characteristics particular to specific genotypes became apparent. LV6-57 patients were more likely to have renal involvement and to harbor a translocation 11;14. LV3-01 patients were less likely to have advanced cardiac disease and renal involvement. LV2-14 patients were more likely to have peripheral nerve involvement, an intact circulating immunoglobulin, and lower circulating dFLC. LV1-44 patients were more likely to have cardiac involvement. KV1-33 patients had more liver involvement and higher circulating dFLC. Finally, KV1-05 was associated with inferior overall survival but not independently of cardiac stage. IGVL gene usage appears to provide clues about disease pathophysiology and tissue tropism. LC-MS is a high-throughput and low-resource technique that can be used to identify IGVL gene from clinical tissue specimens.

Original languageEnglish (US)
Pages (from-to)299-306
Number of pages8
JournalBlood
Volume129
Issue number3
DOIs
StatePublished - Jan 19 2017

Fingerprint

Immunoglobulin Light Chains
Immunoglobulin Genes
Amyloidosis
Mass spectrometry
Immunoglobulins
Mass Spectrometry
Genes
Liquid chromatography
Tissue
Tropism
Ports and harbors
Tandem Mass Spectrometry
Liquid Chromatography
Liver
Bone
Fats
Throughput
Kidney
Peripheral Nerves
Adipose Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry. / Kourelis, Taxiarchis; Dasari, Surendra; Theis, Jason D.; Ramirez-Alvarado, Marina; Kurtin, Paul J.; Gertz, Morie; Zeldenrust, Steven R.; Zenka, Roman M.; Dogan, Ahmet; Dispenzieri, Angela.

In: Blood, Vol. 129, No. 3, 19.01.2017, p. 299-306.

Research output: Contribution to journalArticle

@article{f3cb37d59cd54e52b510408dabcfef42,
title = "Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry",
abstract = "The goal of this study was to investigate the frequency of use of light-chain variable region (IGVL) genes among patients with systemic (ALS) and localized (ALL) amyloidosis and to assess for associations between IGVL gene usage and organ tropism. We evaluated clinic charts from 821 AL patients seen at the Mayo Clinic who had bone marrow, fat pad, and solid organ tissue samples typed by liquid chromatography tandem mass spectrometry (LC-MS). We identified 701 patients with ALS and 120 with ALL. Overall, we were able to identify an IGVL gene in 87 (72{\%}) patients with ALL and 573 (82{\%}) patients with ALS. When compared with ALL, LV6-57 was more common, whereas KV3-20 and heavy-chain codeposition were less common in ALS. In this large series of ALS, characteristics particular to specific genotypes became apparent. LV6-57 patients were more likely to have renal involvement and to harbor a translocation 11;14. LV3-01 patients were less likely to have advanced cardiac disease and renal involvement. LV2-14 patients were more likely to have peripheral nerve involvement, an intact circulating immunoglobulin, and lower circulating dFLC. LV1-44 patients were more likely to have cardiac involvement. KV1-33 patients had more liver involvement and higher circulating dFLC. Finally, KV1-05 was associated with inferior overall survival but not independently of cardiac stage. IGVL gene usage appears to provide clues about disease pathophysiology and tissue tropism. LC-MS is a high-throughput and low-resource technique that can be used to identify IGVL gene from clinical tissue specimens.",
author = "Taxiarchis Kourelis and Surendra Dasari and Theis, {Jason D.} and Marina Ramirez-Alvarado and Kurtin, {Paul J.} and Morie Gertz and Zeldenrust, {Steven R.} and Zenka, {Roman M.} and Ahmet Dogan and Angela Dispenzieri",
year = "2017",
month = "1",
day = "19",
doi = "10.1182/blood-2016-10-743997",
language = "English (US)",
volume = "129",
pages = "299--306",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

AU - Kourelis, Taxiarchis

AU - Dasari, Surendra

AU - Theis, Jason D.

AU - Ramirez-Alvarado, Marina

AU - Kurtin, Paul J.

AU - Gertz, Morie

AU - Zeldenrust, Steven R.

AU - Zenka, Roman M.

AU - Dogan, Ahmet

AU - Dispenzieri, Angela

PY - 2017/1/19

Y1 - 2017/1/19

N2 - The goal of this study was to investigate the frequency of use of light-chain variable region (IGVL) genes among patients with systemic (ALS) and localized (ALL) amyloidosis and to assess for associations between IGVL gene usage and organ tropism. We evaluated clinic charts from 821 AL patients seen at the Mayo Clinic who had bone marrow, fat pad, and solid organ tissue samples typed by liquid chromatography tandem mass spectrometry (LC-MS). We identified 701 patients with ALS and 120 with ALL. Overall, we were able to identify an IGVL gene in 87 (72%) patients with ALL and 573 (82%) patients with ALS. When compared with ALL, LV6-57 was more common, whereas KV3-20 and heavy-chain codeposition were less common in ALS. In this large series of ALS, characteristics particular to specific genotypes became apparent. LV6-57 patients were more likely to have renal involvement and to harbor a translocation 11;14. LV3-01 patients were less likely to have advanced cardiac disease and renal involvement. LV2-14 patients were more likely to have peripheral nerve involvement, an intact circulating immunoglobulin, and lower circulating dFLC. LV1-44 patients were more likely to have cardiac involvement. KV1-33 patients had more liver involvement and higher circulating dFLC. Finally, KV1-05 was associated with inferior overall survival but not independently of cardiac stage. IGVL gene usage appears to provide clues about disease pathophysiology and tissue tropism. LC-MS is a high-throughput and low-resource technique that can be used to identify IGVL gene from clinical tissue specimens.

AB - The goal of this study was to investigate the frequency of use of light-chain variable region (IGVL) genes among patients with systemic (ALS) and localized (ALL) amyloidosis and to assess for associations between IGVL gene usage and organ tropism. We evaluated clinic charts from 821 AL patients seen at the Mayo Clinic who had bone marrow, fat pad, and solid organ tissue samples typed by liquid chromatography tandem mass spectrometry (LC-MS). We identified 701 patients with ALS and 120 with ALL. Overall, we were able to identify an IGVL gene in 87 (72%) patients with ALL and 573 (82%) patients with ALS. When compared with ALL, LV6-57 was more common, whereas KV3-20 and heavy-chain codeposition were less common in ALS. In this large series of ALS, characteristics particular to specific genotypes became apparent. LV6-57 patients were more likely to have renal involvement and to harbor a translocation 11;14. LV3-01 patients were less likely to have advanced cardiac disease and renal involvement. LV2-14 patients were more likely to have peripheral nerve involvement, an intact circulating immunoglobulin, and lower circulating dFLC. LV1-44 patients were more likely to have cardiac involvement. KV1-33 patients had more liver involvement and higher circulating dFLC. Finally, KV1-05 was associated with inferior overall survival but not independently of cardiac stage. IGVL gene usage appears to provide clues about disease pathophysiology and tissue tropism. LC-MS is a high-throughput and low-resource technique that can be used to identify IGVL gene from clinical tissue specimens.

UR - http://www.scopus.com/inward/record.url?scp=85019078470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019078470&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-10-743997

DO - 10.1182/blood-2016-10-743997

M3 - Article

C2 - 27856462

AN - SCOPUS:85019078470

VL - 129

SP - 299

EP - 306

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -