Quantification of peptides from immunoglobulin constant and variable regions by LC-MRM MS for assessment of multiple myeloma patients
Article first published online: 15 SEP 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Special Issue: Focus on Animal Models for Translation Proteomics
Volume 8, Issue 9-10, pages 783–795, October 2014
How to Cite
Remily-Wood, E. R., Benson, K., Baz, R. C., Chen, Y. A., Hussein, M., Hartley-Brown, M. A., Sprung, R. W., Perez, B., Liu, R. Z., Yoder, S. J., Teer, J. K., Eschrich, S. A. and Koomen, J. M. (2014), Quantification of peptides from immunoglobulin constant and variable regions by LC-MRM MS for assessment of multiple myeloma patients. Prot. Clin. Appl., 8: 783–795. doi: 10.1002/prca.201300077
- Issue published online: 2 OCT 2014
- Article first published online: 15 SEP 2014
- Accepted manuscript online: 10 APR 2014 05:56AM EST
- Manuscript Accepted: 3 APR 2014
- Manuscript Revised: 5 MAR 2014
- Manuscript Received: 20 AUG 2013
- National Cancer Institute. Grant Number: R21-CA141285
- US Army Medical Research and Materiel Command. Grant Numbers: DAMD17-02-2-0051, W81XWH-08-2-0101
- National Functional Genomics Center
- National Cancer Institute. Grant Number: P30-CA076292
- Bankhead–Coley Cancer Research program of the Florida Department of Health. Grant Numbers: 06BS-02-9614, 09BE-04
- Ig quantification;
- LC-MRM MS;
- Multiple myeloma
Quantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM).
Using LC-MS/MS data, Ig constant region peptides, and transitions were selected for LC-MRM MS. Quantitative assays were used to assess Igs in serum from 83 patients. RNA sequencing and peptide-based LC-MRM are used to define peptides for quantification of the disease-specific Ig.
LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1–4, IgA1–2, IgM, IgD, and IgE, as well as kappa (κ) and lambda (λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 MM cell line and two MM patients.
Conclusions and clinical relevance
LC-MRM assays targeting constant region peptides determine the type and isoform of the involved Ig and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher inter-assay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques.