Effect of Natalizumab Treatment on Circulating Plasmacytoid Dendritic Cells: A Cross-Sectional Observational Study in Patients with Multiple Sclerosis

Dendritic cells (DCs) serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS). Frequency and phenotype of myeloid and...

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Published in:PloS one Vol. 9; no. 7; p. e103716
Main Authors: Kivisäkk, Pia, Francois, Katiana, Mbianda, Julvet, Gandhi, Roopali, Weiner, Howard L., Khoury, Samia J.
Format: Journal Article
Language:English
Published: United States Public Library of Science 30.07.2014
Public Library of Science (PLoS)
Subjects:
Adaptive immunity
Adult
Aged
Analysis
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
B cells
Biological response modifiers
Biology and Life Sciences
Blood
Care and treatment
CCR7 protein
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - physiology
Cell activation
Cell differentiation
Cell Differentiation - drug effects
Cells, Cultured
CpG islands
Cross-Sectional Studies
Cytokines
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - physiology
Differentiation (biology)
Female
Gene Expression
Genotype & phenotype
Histocompatibility antigen HLA
Homology
Hospitals
Humans
Immunity
Immunologic Factors - pharmacology
Immunologic Factors - therapeutic use
Immunotherapy
Integrins
Interferon
Interleukin 12
Interleukin 6
Lymphatic system
Lymphocytes
Lymphocytes T
Male
Medical research
Medical schools
Middle Aged
Monoclonal antibodies
Multiple sclerosis
Multiple Sclerosis - blood
Multiple Sclerosis - drug therapy
Multiple Sclerosis - immunology
Natalizumab
Observational studies
Oligonucleotides
Patients
Peripheral blood
Peripheral circulation
Phenotypes
Research and Analysis Methods
Rodents
Studies
T cell receptors
T cells
TLR9 protein
Toll-like receptors
Young Adult
United States > US
Massachusetts
ISSN:1932-6203, 1932-6203
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Summary:Dendritic cells (DCs) serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS). Frequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively) were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment. We observed that NTZ treatment was associated with a 25-50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation. Our study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood.
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Conceived and designed the experiments: PK KF JM RG HLW SJK. Performed the experiments: PK KF JM. Analyzed the data: PK KF JM. Wrote the paper: PK KF JM RG HLW SJK.
Competing Interests: This study was supported by an investigator initiated research grant from Biogen Idec. Dr Kivisakk has received research support from EMD Serono. Dr Gandhi has received research support from EMD Serono, Novartis and Biogen. Dr Weiner has served as a consultant for Teva Neurosciences, Novartis, Biogen and EMD Serono, and has received grant support from EMD Sergono. Dr Khoury has served as a consultant for Epivax and Novartis. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0103716