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Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis
M Krumbholz1, I Meinl, T Kümpfel
1Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany.
Neurology
|October 22, 2008
Summary
Natalizumab therapy for multiple sclerosis (MS) significantly increases circulating B cells, particularly immature pre-B cells. This suggests B cells may play a key role in natalizumab
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Natalizumab is an anti-alpha4 integrin antibody used to treat multiple sclerosis (MS).
- Its mechanism of action is thought to involve blocking T cell and monocyte entry into the brain.
- The specific effects of natalizumab on B cells in MS pathogenesis are not well understood.
Purpose of the Study:
- To investigate the impact of natalizumab on B cell subsets in patients with relapsing-remitting MS.
- To determine if B cells are a significant target of natalizumab's action.
Main Methods:
- Serial blood samples were collected from 17 natalizumab-treated MS patients, 10 untreated MS patients, and 13 healthy donors.
- Flow cytometry was used to quantify mature and immature lymphocyte subsets (CD3, CD4, CD8, CD19, CD138, CD10).
- Quantitative PCR analyzed transcripts for immature hematopoietic cells (CD34, Vprebeta1, DNTT).
Main Results:
- Natalizumab treatment led to a significant increase in mature B cells (CD19+) and an even greater increase in immature pre-B cells (CD19+CD10+).
- These increases were more pronounced than those observed for other lymphocytes and monocytes.
- Elevated transcripts for lymphocyte precursors (Vprebeta1, DNTT) were observed, exceeding those for CD34.
Conclusions:
- Natalizumab therapy prominently elevates circulating B cells, especially pre-B cells, in MS patients.
- These findings suggest that B cells may be involved in the therapeutic effects and potential side effects of natalizumab.
- Further research into B cell modulation by natalizumab is warranted.
