Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum

Lidong He, Lissa C. Anderson, David R. Barnidge, David L. Murray, Surendra Dasari, Angela Dispenzieri, Christopher L. Hendrickson, Alan G. Marshall

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT-ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal immunoglobulin heavy chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal immunoglobulins with polyclonal immunoglobulins background.

Original languageEnglish (US)
Pages (from-to)3263-3269
Number of pages7
JournalAnalytical Chemistry
Volume91
Issue number5
DOIs
StatePublished - Mar 5 2019

Fingerprint

Immunoglobulin Light Chains
Cyclotron resonance
Immunoglobulins
Fourier transforms
Ions
Plasmas
Immunoglobulin Heavy Chains
Bone
Blood
Genes
Cells
Amino Acids
Testing

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum. / He, Lidong; Anderson, Lissa C.; Barnidge, David R.; Murray, David L.; Dasari, Surendra; Dispenzieri, Angela; Hendrickson, Christopher L.; Marshall, Alan G.

In: Analytical Chemistry, Vol. 91, No. 5, 05.03.2019, p. 3263-3269.

Research output: Contribution to journalArticle

He, Lidong ; Anderson, Lissa C. ; Barnidge, David R. ; Murray, David L. ; Dasari, Surendra ; Dispenzieri, Angela ; Hendrickson, Christopher L. ; Marshall, Alan G. / Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum. In: Analytical Chemistry. 2019 ; Vol. 91, No. 5. pp. 3263-3269.
@article{81b363c666284eab9c5a2d5fd88642c2,
title = "Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum",
abstract = "The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51{\%}, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT-ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100{\%} matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal immunoglobulin heavy chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal immunoglobulins with polyclonal immunoglobulins background.",
author = "Lidong He and Anderson, {Lissa C.} and Barnidge, {David R.} and Murray, {David L.} and Surendra Dasari and Angela Dispenzieri and Hendrickson, {Christopher L.} and Marshall, {Alan G.}",
year = "2019",
month = "3",
day = "5",
doi = "10.1021/acs.analchem.8b03294",
language = "English (US)",
volume = "91",
pages = "3263--3269",
journal = "Analytical Chemistry",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum

AU - He, Lidong

AU - Anderson, Lissa C.

AU - Barnidge, David R.

AU - Murray, David L.

AU - Dasari, Surendra

AU - Dispenzieri, Angela

AU - Hendrickson, Christopher L.

AU - Marshall, Alan G.

PY - 2019/3/5

Y1 - 2019/3/5

N2 - The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT-ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal immunoglobulin heavy chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal immunoglobulins with polyclonal immunoglobulins background.

AB - The current five-year survival rate for systemic AL amyloidosis or multiple myeloma is ∼51%, indicating the urgent need for better diagnosis methods and treatment plans. Here, we describe highly specific and sensitive top-down and middle-down MS/MS methods owning the advantages of fast sample preparation, ultrahigh mass accuracy, and extensive residue cleavages with 21 telsa FT-ICR MS/MS. Unlike genomic testing, which requires bone marrow aspiration and may fail to identify all monoclonal immunoglobulins produced by the body, the present method requires only a blood draw. In addition, circulating monoclonal immunoglobulins spanning the entire population are analyzed and reflect the selection of germline sequence by B cells. The monoclonal immunoglobulin light chain FR2-CDR2-FR3 was sequenced by database-aided de novo MS/MS and 100% matched the gene sequencing result, except for two amino acids with isomeric counterparts, enabling accurate germline sequence classification. The monoclonal immunoglobulin heavy chains were also classified into specific germline sequences based on the present method. This work represents the first application of top/middle-down MS/MS sequencing of endogenous human monoclonal immunoglobulins with polyclonal immunoglobulins background.

UR - http://www.scopus.com/inward/record.url?scp=85062388620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062388620&partnerID=8YFLogxK

U2 - 10.1021/acs.analchem.8b03294

DO - 10.1021/acs.analchem.8b03294

M3 - Article

VL - 91

SP - 3263

EP - 3269

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 5

ER -