TY - JOUR
T1 - Novel mechanisms of immune modulation of natalizumab in multiple sclerosis patients
AU - Skarica, Mario
AU - Eckstein, Christopher
AU - Whartenby, Katharine A.
AU - Calabresi, Peter A.
PY - 2011/6
Y1 - 2011/6
N2 - The goal of this study was to investigate the effects of natalizumab therapy on the immune cell composition and phenotype in the blood of relapsing MS patients treated over the course of 12. months. We collected peripheral blood from 26 RRMS patients before treatment onset, and then 6 and 12. months after therapy. PBMC was isolated and then analyzed for phenotypic characteristics by FACS and for cytokine production by ELISA.The results of our studies showed changes in both numbers and activation states of immune cells following therapy. These changes were observed at the 6month timepoint and generally persisted through the 12month timepoint. The proportions of NK cells (CD3-CD56+) and hematopoetic stem cells (CD34+lin-) were increased after natalizumab treatment. Decreases were noted in numbers of CD14+ monocytes, and possibly their migratory potential, since their expression levels of α4β1 were decreased. Relative numbers of CD20+ B cells were increased, but the proportion of CD20+ cells expressing high levels of α4β1 integrin was decreased. While proportions of CD4+ and CD8+ T cells did not change, the percentage of cells expressing α4β1 integrin was significantly decreased for both subsets.Natalizumab therapy produces a number of phenotypic changes in the immune composition of peripheral blood. These changes may help to explain both the mechanisms of action of natalizumab and also shed light on the potential for the observed increase in PML in these patients.
AB - The goal of this study was to investigate the effects of natalizumab therapy on the immune cell composition and phenotype in the blood of relapsing MS patients treated over the course of 12. months. We collected peripheral blood from 26 RRMS patients before treatment onset, and then 6 and 12. months after therapy. PBMC was isolated and then analyzed for phenotypic characteristics by FACS and for cytokine production by ELISA.The results of our studies showed changes in both numbers and activation states of immune cells following therapy. These changes were observed at the 6month timepoint and generally persisted through the 12month timepoint. The proportions of NK cells (CD3-CD56+) and hematopoetic stem cells (CD34+lin-) were increased after natalizumab treatment. Decreases were noted in numbers of CD14+ monocytes, and possibly their migratory potential, since their expression levels of α4β1 were decreased. Relative numbers of CD20+ B cells were increased, but the proportion of CD20+ cells expressing high levels of α4β1 integrin was decreased. While proportions of CD4+ and CD8+ T cells did not change, the percentage of cells expressing α4β1 integrin was significantly decreased for both subsets.Natalizumab therapy produces a number of phenotypic changes in the immune composition of peripheral blood. These changes may help to explain both the mechanisms of action of natalizumab and also shed light on the potential for the observed increase in PML in these patients.
KW - Autoimmunity
KW - Cytokines
KW - Immunomodulation
KW - Multiple sclerosis
KW - Natalizumab
KW - PML
UR - http://www.scopus.com/inward/record.url?scp=79957973246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957973246&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2011.02.010
DO - 10.1016/j.jneuroim.2011.02.010
M3 - Article
C2 - 21550672
AN - SCOPUS:79957973246
SN - 0165-5728
VL - 235
SP - 70
EP - 76
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -