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Copyright © 2010 American Medical Association. All rights reserved. From: Changes in B- and T-Lymphocyte and Chemokine Levels With Rituximab Treatment in Multiple Sclerosis Arch Neurol. 2010;67(6):707-714. doi:10.1001/archneurol.2010.99 Figure Legend: Study protocol. A screening phase (weeks −8, −4, and 0) was followed by the treatment period. Thirty subjects each received 4 doses of rituximab (375 mg/m2) 1 week apart. Magnetic resonance imaging (MRI) of the brain with and without gadolinium and the Multiple Sclerosis Functional Composite (MSFC) were assessed serially in all subjects. At least 3 “practice” MSFC tests were performed before the baseline MSFC test at week 1 (just before the first infusion). Twenty-six subjects underwent cerebrospinal fluid sampling 1 week before and 24 to 30 weeks following rituximab treatment. Date of download: 10/25/2017 Copyright © 2010 American Medical Association. All rights reserved.

Copyright © 2010 American Medical Association. All rights reserved. From: Changes in B- and T-Lymphocyte and Chemokine Levels With Rituximab Treatment in Multiple Sclerosis Arch Neurol. 2010;67(6):707-714. doi:10.1001/archneurol.2010.99 Figure Legend: Effects of rituximab therapy on B- and T-cell levels in the cerebrospinal fluid (CSF) and blood. The B and T cells in the CSF and blood were counted before and after rituximab treatment by flow cytometry. A, Levels of B cells in the CSF decreased after treatment (P < .0001 by Wilcoxon matched pairs test). B, CD19+ B cells were eliminated from the blood by 8 weeks in all subjects, and most remained depleted of B cells at weeks 24 to 30. C, Numbers of CD3+ T cells in the CSF decreased in 21 of the 26 subjects who underwent the lumbar puncture after rituximab (P = .0001, Wilcoxon matched pairs test). D, The number of T cells in the blood also showed a small but significant reduction after rituximab treatment (P = .0008 by Wilcoxon matched pairs test). Date of download: 10/25/2017 Copyright © 2010 American Medical Association. All rights reserved.

Copyright © 2010 American Medical Association. All rights reserved. From: Changes in B- and T-Lymphocyte and Chemokine Levels With Rituximab Treatment in Multiple Sclerosis Arch Neurol. 2010;67(6):707-714. doi:10.1001/archneurol.2010.99 Figure Legend: Effect of rituximab therapy on CXCL13 and CCL19 levels in the cerebrospinal fluid (CSF) and blood. A, Levels of CXCL13 in the CSF were measured by enzyme-linked immunosorbent assay (ELISA) before and after rituximab treatment in 23 subjects, and the levels decreased in all but 1 case (P = .002). B, Serum levels of CXCL13 (n = 25 pairs) also declined significantly (P < .0001), with a decrease in 21 subjects, an increase in 2, and no change in 2. C, Levels of CCL19 were measured by ELISA in 26 sets of paired CSF and, D, in 13 sets of paired serum samples obtained before and after rituximab treatment. Levels of CCL19 in the CSF and serum significantly declined after rituximab treatment (P = .03 and P = .008, respectively). Date of download: 10/25/2017 Copyright © 2010 American Medical Association. All rights reserved.

Copyright © 2010 American Medical Association. All rights reserved. From: Changes in B- and T-Lymphocyte and Chemokine Levels With Rituximab Treatment in Multiple Sclerosis Arch Neurol. 2010;67(6):707-714. doi:10.1001/archneurol.2010.99 Figure Legend: The degree of cerebrospinal fluid (CSF) T-cell level reduction correlated with the degree of CSF CXCL13 level decrease. The percentage of changes of CD3+ T-cell levels and CXCL13 levels in CSF were determined for each patient before vs after rituximab treatment (n = 23) and were found to be correlated (r = 0.45; P = .03, Spearman rank correlation). The best-fit line is shown. Date of download: 10/25/2017 Copyright © 2010 American Medical Association. All rights reserved.