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

• Published in: Nature medicine Vol. 14; no. 6; pp. 688 - 693
• Main Authors: Wekerle, Hartmut, Mentele, Reinhard, Kellermann, Josef, Malotka, Joachim, Obermeier, Birgit, Lottspeich, Friedrich, Dornmair, Klaus, Kümpfel, Tania, Hohlfeld, Reinhard
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2008; Nature Publishing Group
• Subjects: Amino Acid Sequence; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Body fluids; Cancer Research; Care and treatment; Cellular biology; Cerebrospinal fluid; Cerebrospinal Fluid Proteins - genetics; Cerebrospinal Fluid Proteins - immunology; Databases, Genetic; Diagnosis; Gels; Health aspects; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Light Chains - genetics; Immunoglobulin Variable Region - genetics; Immunoglobulins; Infectious Diseases; Isoelectric Focusing; Mass Spectrometry; Medical research; Metabolic Diseases; Molecular Medicine; Molecular Sequence Data; Multiple sclerosis; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - immunology; Mutation; Neurosciences; Oligoclonal Bands - genetics; Oligoclonal Bands - immunology; Peptides; Proteome - analysis; Proteomics; Research methodology; Risk factors; Sequence Homology, Amino Acid; Spine; technical-report; Transcription, Genetic; Germany
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm1714

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.