Analytical and Bioanalytical Chemistry

, Volume 389, Issue 5, pp 1397–1407 | Cite as

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 R. Emmett
  • Alan G. Marshall
  • Jan Novak
Paper in Forefront

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

ICR FT-ICR FTMS O-Glycosylation Electron capture dissociation 

Notes

Acknowledgments

The authors thank Monica Stinnett, Stephanie Wall, John P. Quinn, Stacy Hall, Rose Kulhavy, and Rhubell Brown for their excellent technical assistance. We also thank Dr. Kristina Håkansson for helpful discussions. This work was supported by grants from the National Institutes of Health (RR17261, DK61525, DK71802, DK78244, DE13694, DK64400, and DK47322) the National Science Foundation (DMR-00–841730), the University of Alabama at Birmingham, the National High Magnetic Field Laboratory, and Florida State University.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Matthew B. Renfrow
    • 1
  • C. Logan Mackay
    • 2
    • 7
  • Michael J. Chalmers
    • 2
    • 8
  • Bruce A. Julian
    • 3
    • 4
  • Jiri Mestecky
    • 3
    • 4
  • Mogens Kilian
    • 5
  • Knud Poulsen
    • 5
  • Mark R. Emmett
    • 2
    • 6
  • Alan G. Marshall
    • 2
    • 6
  • Jan Novak
    • 4
  1. 1.UAB Biomedical FT-ICR MS Laboratory, Department of Biochemistry and Molecular GeneticsUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.National High Magnetic Field LaboratoryFlorida State UniversityTallahasseeUSA
  3. 3.Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of MicrobiologyUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Department of Medical Microbiology and ImmunologyAarhus UniversityAarhusDenmark
  6. 6.Member of the Department of Chemistry and BiochemistryFlorida State UniversityTallahasseeUSA
  7. 7.Department of ChemistryUniversity of EdinburghEdinburghScotland
  8. 8.Department of Molecular TherapeuticsThe Scripps Research InstituteJupiterUSA

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