Natalizumab and Impedance of the Homing of CD34+ Hematopoietic Progenitors

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.