Document Detail

Differential effects of decoy receptor- and antibody-mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients.
MedLine Citation:
PMID:  23031059     Owner:  NLM     Status:  MEDLINE    
Our aim was to clarify if anti-tumour necrosis factor (TNF) drugs have effect on expression of three splice forms of FoxP3 mRNA in blood CD4+ T cells from rheumatoid arthritis (RA) patients compared with healthy controls. Forty-five rheumatoid arthritis patients treated with anti-TNF therapy were investigated in a 12-week prospective cohort study. FoxP3 isoforms, CD25 and CTLA-4 mRNA in blood CD4+ T cells were measured with quantitative real-time PCR. Patients benefitting from the treatment, based on changes in DAS28 scores, revealed a significant decrease in expression of full-length FoxP3 following 12 weeks treatment with TNF receptor 2 fusion protein (Etanercept), but not following treatment with anti-TNF antibodies (Adalimumab or Infliximab). A partial normalization of the CTLA-4/FoxP3fl ratio and a correlation between clinical improvement and change in FoxP3 mRNA expression were also seen in Etanercept responders. These changes were not observed in responsive patients treated with the antibody therapies. Our data suggest that TNF decoy receptor and anti-TNF antibodies differ in their effect on FoxP3 expression in responsive patients. As Etanercept binds both TNF-α and Lymphotoxin-α (LT-α), whereas the antibodies only target TNF-α, LT-α may regulate FoxP3 expression in a subset of RA patients. Our findings support the view that anti-TNF treatment is mainly symptomatic.
L Rebekka Ryder; Lars P Ryder; Else M Bartels; Anders Woetmann; Hans O Madsen; Niels Ødum; Bente Danneskiold-Samsøe; Søren Ribel-Madsen; Henning Bliddal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-23
Journal Detail:
Title:  APMIS : acta pathologica, microbiologica, et immunologica Scandinavica     Volume:  121     ISSN:  1600-0463     ISO Abbreviation:  APMIS     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-26     Completed Date:  2013-05-13     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  8803400     Medline TA:  APMIS     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  337-47     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors APMIS © 2012 APMIS.
The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Frederiksberg, Denmark.
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MeSH Terms
Aged, 80 and over
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized / therapeutic use
Arthritis, Rheumatoid / drug therapy*,  immunology
Cohort Studies
Forkhead Transcription Factors / genetics*
Immunoglobulin G / therapeutic use
Middle Aged
Prospective Studies
RNA, Messenger / blood
Receptors, Tumor Necrosis Factor / therapeutic use
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Immunoglobulin G; 0/RNA, Messenger; 0/Receptors, Tumor Necrosis Factor; 0/Tumor Necrosis Factor-alpha; 0/infliximab; 185243-69-0/TNFR-Fc fusion protein; FYS6T7F842/adalimumab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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