Differential effects of decoy receptor- and antibody-mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients
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Differential effects of decoy receptor- and antibody-mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients. / Ryder, L Rebekka; Ryder, Lars P; Bartels, Else M; Woetmann, Anders; Madsen, Hans O; Ødum, Niels; Danneskiold-Samsøe, Bente; Ribel-Madsen, Søren; Bliddal, Henning.
In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, Vol. 121, No. 4, 04.2013, p. 337-47.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Differential effects of decoy receptor- and antibody-mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients
AU - Ryder, L Rebekka
AU - Ryder, Lars P
AU - Bartels, Else M
AU - Woetmann, Anders
AU - Madsen, Hans O
AU - Ødum, Niels
AU - Danneskiold-Samsøe, Bente
AU - Ribel-Madsen, Søren
AU - Bliddal, Henning
N1 - © 2012 The Authors APMIS © 2012 APMIS.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Monoclonal
KW - Antibodies, Monoclonal, Humanized
KW - Arthritis, Rheumatoid
KW - Cohort Studies
KW - Female
KW - Forkhead Transcription Factors
KW - Humans
KW - Immunoglobulin G
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - RNA, Messenger
KW - Receptors, Tumor Necrosis Factor
KW - Tumor Necrosis Factor-alpha
U2 - 10.1111/apm.12004
DO - 10.1111/apm.12004
M3 - Journal article
C2 - 23031059
VL - 121
SP - 337
EP - 347
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 4
ER -
ID: 117552066