Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry

Implications for IgA nephropathy

Matthew B. Renfrow, C. Logan MacKay, Michael J. Chalmers, Bruce A. Julian, Jiri Mestecky, Mogens Kilian, Knud Poulsen, Mark Emmett, Alan G. Marshall, Jan Novak

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible.

Original languageEnglish (US)
Pages (from-to)1397-1407
Number of pages11
JournalAnalytical and Bioanalytical Chemistry
Volume389
Issue number5
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Cyclotrons
Myeloma Proteins
Cyclotron resonance
Fourier Analysis
Immunoglobulin A
Mass spectrometry
Polysaccharides
Mass Spectrometry
Fourier transforms
Ions
Hinges
Glycopeptides
Electrons
Glycosylation
Liquid chromatography
Glomerulonephritis
Tandem Mass Spectrometry
Antigen-Antibody Complex
Galactose
Liquid Chromatography

Keywords

  • Electron capture dissociation
  • FT-ICR
  • FTMS
  • ICR
  • O-glycosylation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Clinical Biochemistry

Cite this

Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry : Implications for IgA nephropathy. / Renfrow, Matthew B.; MacKay, C. Logan; Chalmers, Michael J.; Julian, Bruce A.; Mestecky, Jiri; Kilian, Mogens; Poulsen, Knud; Emmett, Mark; Marshall, Alan G.; Novak, Jan.

In: Analytical and Bioanalytical Chemistry, Vol. 389, No. 5, 11.2007, p. 1397-1407.

Research output: Contribution to journalArticle

Renfrow, Matthew B. ; MacKay, C. Logan ; Chalmers, Michael J. ; Julian, Bruce A. ; Mestecky, Jiri ; Kilian, Mogens ; Poulsen, Knud ; Emmett, Mark ; Marshall, Alan G. ; Novak, Jan. / Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry : Implications for IgA nephropathy. In: Analytical and Bioanalytical Chemistry. 2007 ; Vol. 389, No. 5. pp. 1397-1407.
@article{77ae16e17b434f6892351fd10577c9a5,
title = "Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: Implications for IgA nephropathy",
abstract = "IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible.",
keywords = "Electron capture dissociation, FT-ICR, FTMS, ICR, O-glycosylation",
author = "Renfrow, {Matthew B.} and MacKay, {C. Logan} and Chalmers, {Michael J.} and Julian, {Bruce A.} and Jiri Mestecky and Mogens Kilian and Knud Poulsen and Mark Emmett and Marshall, {Alan G.} and Jan Novak",
year = "2007",
month = "11",
doi = "10.1007/s00216-007-1500-z",
language = "English (US)",
volume = "389",
pages = "1397--1407",
journal = "Fresenius Zeitschrift fur Analytische Chemie",
issn = "0016-1152",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry

T2 - Implications for IgA nephropathy

AU - Renfrow, Matthew B.

AU - MacKay, C. Logan

AU - Chalmers, Michael J.

AU - Julian, Bruce A.

AU - Mestecky, Jiri

AU - Kilian, Mogens

AU - Poulsen, Knud

AU - Emmett, Mark

AU - Marshall, Alan G.

AU - Novak, Jan

PY - 2007/11

Y1 - 2007/11

N2 - IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible.

AB - IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI-ECD fragmentation on an individual IgA1 O-glycopeptide from an IgA1 HR preparation that is reproducible for each IgA1 myeloma protein. These results suggest that future analysis of IgA1 HR from IgAN patients and normal healthy controls should be feasible.

KW - Electron capture dissociation

KW - FT-ICR

KW - FTMS

KW - ICR

KW - O-glycosylation

UR - http://www.scopus.com/inward/record.url?scp=35648929345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35648929345&partnerID=8YFLogxK

U2 - 10.1007/s00216-007-1500-z

DO - 10.1007/s00216-007-1500-z

M3 - Article

VL - 389

SP - 1397

EP - 1407

JO - Fresenius Zeitschrift fur Analytische Chemie

JF - Fresenius Zeitschrift fur Analytische Chemie

SN - 0016-1152

IS - 5

ER -