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Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis

Nature Medicine volume 14, pages 688–693 (2008)Cite this article

Abstract

We describe a method for correlating the immunoglobulin (Ig) proteomes with the B cell transcriptomes in human fluid and tissue samples, using multiple sclerosis as a paradigm. Oligoclonal Ig bands and elevated numbers of clonally expanded B cells in the cerebrospinal fluid (CSF) are diagnostic hallmarks of multiple sclerosis. Here we compared the Ig transcriptomes of B cells with the corresponding Ig proteomes in CSF samples from four subjects with multiple sclerosis. We created individual Ig transcriptome databases that contained the subject-specific mutations introduced by V(D)J recombination and somatic hypermutation and then searched the CSF for corresponding characteristic peptides by mass spectrometry. In each sample, the Ig transcriptomes and proteomes strongly overlapped, showing that CSF B cells indeed produce the oligoclonal Ig bands. This approach can be applied to other organ-specific diagnostic fluid or tissue samples to compare the Ig transcripts of local B cells with the corresponding antibody proteomes of individual subjects.

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Figure 1: Matching IgG transcriptome and proteome of multiple sclerosis subject NS-52.
Figure 2: Matching IgG transcriptome and proteome of multiple sclerosis subject JN-02.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft grant SFB 571-A1 and the Hermann and Lilly Schilling Foundation. We thank M. Wick and M. Krumbholz for valuable support and J. Benson for editing the manuscript.

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Authors and Affiliations

  1. Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, D-81377, Munich, Germany

    Birgit Obermeier, Reinhard Mentele, Tania Kümpfel, Reinhard Hohlfeld & Klaus Dornmair

  2. Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, Martinsried, D-82152, Germany

    Birgit Obermeier, Joachim Malotka, Hartmut Wekerle, Reinhard Hohlfeld & Klaus Dornmair

  3. Department for Protein Analytics, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, Martinsried, D-82152, Germany

    Reinhard Mentele, Josef Kellermann & Friedrich Lottspeich

Authors
  1. Birgit Obermeier
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  2. Reinhard Mentele
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  3. Joachim Malotka
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  8. Reinhard Hohlfeld
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  9. Klaus Dornmair
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Contributions

B.O. conducted most of the experiments and prepared the figures, R.M. and J.K. participated in IEF and mass spectrometry experiments, J.M. participated in cloning of Ig chains, T.K. provided CSF samples and clinical data, H.W. and F.L. supervised the project and participated in writing the manuscript and K.D. and R.H. initiated and supervised the project and wrote the manuscript.

Corresponding author

Correspondence to Klaus Dornmair.

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Supplementary Figs. 1–3 and Supplementary Tables 1–4 (PDF 3390 kb)

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Obermeier, B., Mentele, R., Malotka, J. et al. Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Nat Med 14, 688–693 (2008). https://doi.org/10.1038/nm1714

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