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Differential effects of decoy receptor- and antibody-mediated tumour necrosis factor blockage on FoxP3 expression in

L Rebekka Ryder1, Lars P Ryder, Else M Bartels

  • 1The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Frederiksberg, Denmark.

APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
|October 4, 2012
PubMed

Insights

Anti-tumour necrosis factor (TNF) drugs impact FoxP3 mRNA expression differently in rheumatoid arthritis (RA) patients. Etanercept, a TNF decoy receptor, decreased FoxP3 expression, unlike anti-TNF antibodies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation.
  • Anti-tumour necrosis factor (TNF) therapies are widely used for RA management.
  • The precise molecular mechanisms of anti-TNF drugs, particularly their effects on immune cell gene expression, require further elucidation.

Purpose of the Study:

  • To investigate the differential effects of anti-TNF therapies on the expression of FoxP3 mRNA splice variants in CD4+ T cells from RA patients.
  • To compare the impact of TNF receptor 2 fusion protein (Etanercept) versus anti-TNF antibodies (Adalimumab, Infliximab) on FoxP3 expression.
  • To explore the relationship between clinical response to anti-TNF therapy and changes in FoxP3 mRNA levels.

Main Methods:

  • A 12-week prospective cohort study involving 45 RA patients undergoing anti-TNF therapy.
  • Quantitative real-time PCR was used to measure mRNA expression of FoxP3 isoforms, CD25, and CTLA-4 in blood CD4+ T cells.
  • Patients were categorized based on clinical benefit using DAS28 scores.

Main Results:

  • Etanercept responders showed a significant decrease in full-length FoxP3 mRNA expression after 12 weeks.
  • Anti-TNF antibody therapies (Adalimumab, Infliximab) did not significantly alter FoxP3 mRNA expression in responsive patients.
  • A partial normalization of the CTLA-4/FoxP3fl ratio and a correlation between clinical improvement and FoxP3 mRNA changes were observed in Etanercept responders.

Conclusions:

  • TNF decoy receptor (Etanercept) and anti-TNF antibodies exhibit distinct effects on FoxP3 expression in responding RA patients.
  • Lymphotoxin-α (LT-α), which Etanercept targets but antibodies do not, may play a role in regulating FoxP3 expression.
  • The findings suggest that current anti-TNF treatments for RA are primarily symptomatic, with potential differences in their immunomodulatory effects.

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