科研之友
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摘要
Background: Treatment with natalizumab, an antibody blocking the alpha 4-integrin, is associated with increased numbers of circulating CD34(+) cells in the peripheral blood of patients with multiple sclerosis.
Objective: To determine whether natalizumab mobilizes CD34(+) cells from or inhibits homing to the bone marrow (BM).
Design: Fifty-two patients with relapsing-remitting multiple sclerosis treated with natalizumab were included. Flow cytometric analyses; polymerase chain reaction assays for JC (John Cunningham) virus DNA detection; and adhesion, migration, and apoptosis assays of immunomagnetically enriched peripheral blood and BM CD34(+) cells were conducted. A comparison was made with CD34(+) cells from granulocyte colony-stimulating factor-mobilized peripheral blood or steady-state BM of age-and sex-matched healthy donors.
Results: We found adhesion and migration of peripheral blood-derived CD34(+) cells to be reduced. In BM aspirates from natalizumab-treated patients, the cellularity, the proportion, and the adhesive capacity of CD34(+) cells were normal. The JC virus was undetectable.
Conclusions: Natalizumab mediates an increase in circulating CD34(+) cells by interfering with homing to the BM. Thus, CD34(+) cells appear unlikely to represent a source mobilizing JC virus out of the BM in patients treated with natalizumab.
- 出版日期2011-11
