Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis
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 hall...
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| Published in | Nature medicine Vol. 14; no. 6; pp. 688 - 693 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.06.2008
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1078-8956 1546-170X 1546-170X |
| DOI | 10.1038/nm1714 |
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| 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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| AbstractList | 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.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. 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. [PUBLICATION 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. |
| Audience | Academic |
| Author | Mentele, Reinhard Kellermann, Josef Lottspeich, Friedrich Hohlfeld, Reinhard Obermeier, Birgit Dornmair, Klaus Malotka, Joachim Kümpfel, Tania Wekerle, Hartmut |
| Author_xml | – sequence: 1 givenname: Birgit surname: Obermeier fullname: Obermeier, Birgit organization: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 2 givenname: Reinhard surname: Mentele fullname: Mentele, Reinhard organization: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, Department for Protein Analytics, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 3 givenname: Joachim surname: Malotka fullname: Malotka, Joachim organization: Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 4 givenname: Josef surname: Kellermann fullname: Kellermann, Josef organization: Department for Protein Analytics, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 5 givenname: Tania surname: Kümpfel fullname: Kümpfel, Tania organization: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15 – sequence: 6 givenname: Hartmut surname: Wekerle fullname: Wekerle, Hartmut organization: Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 7 givenname: Friedrich surname: Lottspeich fullname: Lottspeich, Friedrich organization: Department for Protein Analytics, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 8 givenname: Reinhard surname: Hohlfeld fullname: Hohlfeld, Reinhard organization: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 – sequence: 9 givenname: Klaus surname: Dornmair fullname: Dornmair, Klaus email: dornmair@neuro.mpg.de organization: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, Department of Neuroimmunology, Max-Planck-Institute of Neurobiology.Max-Planck-Institute of Biochemistry, Am Klopferspitz 18 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18488038$$D View this record in MEDLINE/PubMed |
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| Copyright | Springer Nature America, Inc. 2008 COPYRIGHT 2008 Nature Publishing Group Copyright Nature Publishing Group Jun 2008 |
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| SubjectTerms | 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 |
| Title | Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis |
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