PMID- 25075741
OWN - NLM
STAT- MEDLINE
DCOM- 20151112
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a 
      cross-sectional observational study in patients with multiple sclerosis.
PG  - e103716
LID - 10.1371/journal.pone.0103716 [doi]
LID - e103716
AB  - OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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 alpha4 leading to an increased 
      frequency of activated PDCs in blood.
FAU - Kivisakk, Pia
AU  - Kivisakk P
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts, United States of America.
FAU - Francois, Katiana
AU  - Francois K
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts, United States of America.
FAU - Mbianda, Julvet
AU  - Mbianda J
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts, United States of America.
FAU - Gandhi, Roopali
AU  - Gandhi R
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts, United States of America.
FAU - Weiner, Howard L
AU  - Weiner HL
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts, United States of America; Partners Multiple 
      Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, Massachusetts, United States of America.
FAU - Khoury, Samia J
AU  - Khoury SJ
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts, United States of America; Partners Multiple 
      Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, Massachusetts, United States of America; Abu Haidar 
      Neuroscience Institute, American University of Beirut, Beirut, Lebanon.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20140730
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunologic Factors)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*pharmacology/therapeutic use
MH  - CD4-Positive T-Lymphocytes/drug effects/physiology
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Cross-Sectional Studies
MH  - Dendritic Cells/*drug effects/physiology
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Immunologic Factors/*pharmacology/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/blood/drug therapy/*immunology
MH  - Natalizumab
MH  - Young Adult
PMC - PMC4116240
COIS- 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.
EDAT- 2014/07/31 06:00
MHDA- 2015/11/13 06:00
PMCR- 2014/07/30
CRDT- 2014/07/31 06:00
PHST- 2014/03/05 00:00 [received]
PHST- 2014/07/05 00:00 [accepted]
PHST- 2014/07/31 06:00 [entrez]
PHST- 2014/07/31 06:00 [pubmed]
PHST- 2015/11/13 06:00 [medline]
PHST- 2014/07/30 00:00 [pmc-release]
AID - PONE-D-14-10206 [pii]
AID - 10.1371/journal.pone.0103716 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 30;9(7):e103716. doi: 10.1371/journal.pone.0103716. 
      eCollection 2014.