Differential effects of decoy receptor- and antibody-mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients
- Authors:
-
- Ryder, L Rebekka ;
- Ryder, Lars P ;
- Bartels, Else M ;
-
Woetmann, Anders
;
Close
0000-0002-3008-735X
Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet - Madsen, Hans O ;
- Ødum, Niels ;
-
Danneskiold-Samsøe, Bente
;
Close0000-0003-3710-5212
Section of Orthopaedics and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet - Ribel-Madsen, Søren ;
- Bliddal, Henning
- DOI:
- 10.1111/apm.12004
- Abstract:
- 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.
- Type:
- Journal article
- Language:
- English
- Published in:
- Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica, 2013, Vol 121, Issue 4, p. 337-47
- Keywords:
- Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Cohort Studies; Female; Forkhead Transcription Factors; Humans; Immunoglobulin G; Male; Middle Aged; Prospective Studies; RNA, Messenger; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Forkhead Box P3 Protein; human; FoxP3; rheumatoid arthritis; CD4-positive T-lymphocytes; anti-tumour necrosis factor alpha; Journal Article; Research Support, Non-U.S. Gov't
- Main Research Area:
- Medical science
- Publication Status:
- Published
- Review type:
- Peer Review
- Submission year:
- 2013
- Scientific Level:
- Scientific
- ID:
- 247666265
