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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Vydáno v:Nature medicine Ročník 14; číslo 6; s. 688 - 693
Hlavní autoři: Obermeier, Birgit, Mentele, Reinhard, Malotka, Joachim, Kellermann, Josef, Kümpfel, Tania, Wekerle, Hartmut, Lottspeich, Friedrich, Hohlfeld, Reinhard, Dornmair, Klaus
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Nature Publishing Group US 01.06.2008
Nature Publishing Group
Témata:
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, 1546-170X
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Popis
Shrnutí: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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ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/nm1714