Technical Report abstract
Nature Medicine 14, 688 - 693 (2008)
Published online: 18 May 2008 | doi:10.1038/nm1714
Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis
Birgit Obermeier1,2, Reinhard Mentele1,3, Joachim Malotka2, Josef Kellermann3, Tania Kümpfel1, Hartmut Wekerle2, Friedrich Lottspeich3, Reinhard Hohlfeld1,2 & Klaus Dornmair1,2
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.
- Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany.
- Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
- Department for Protein Analytics, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Correspondence to: Klaus Dornmair1,2 e-mail: dornmair@neuro.mpg.de
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