Adalimumab treatment in Crohn's disease does not induce early changes in regulatory T cells

Abstract

Objective. Anti-TNF-α antibodies has been suggested to modulate regulatory T cell (Treg) percentages in rheumatoid arthritis, but results from studies of Crohn's disease (CD) are conflicting. We investigated dynamic changes of circulating Tregs in CD during treatment with the anti-TNF-α-antibody adalimumab (Humira, Abbott Laboratories A/S, Emdrupvej 28C, DK-2100 Copenhagen). Material and methods. Blood samples from 26 CD patients were analysed using flow cytometry before and 1 and 26 weeks after initiation of adalimumab treatment to determine the percentage of Tregs among CD4+ T cells. Results. In spite of a significant decline in disease activity scores and biochemical markers of inflammation, during the first week of treatment, we did not observe early modulating effects of adalimumab on Treg percentages. However, we found a long-term increase in Treg percentages in responders who had low Treg percentages (<5%) at baseline (p = 0.04). Treg percentage was inversely associated with disease activity (CD activity index or CDAI) (Spearman's rank correlation, ρ = -0.47, p = 0.02). High Treg percentages among CD4+ T cells at baseline predicted clinical response to adalimumab. Conclusions. Adalimumab treatment did not induce early modulatory effects on Treg percentage, even in responders. This finding suggests that adalimumab does not have a direct or selective effect on Tregs. However, Treg percentage was associated with disease activity and high Treg percentage predicted response to adalimumab.

Key Words::

• Adalimumab
• Crohn's disease
• FOXP3 protein
• regulatory T lymphocytes

Acknowledgements

We thank Rikke Andersen for excellent technical assistance. The study was financially supported by an unrestricted grant from Abbott Pharmaceuticals and was also supported by the Danish Colitis-Crohn Foundation, the Beckett Foundation, the Karen Elise Jensen Foundation and the Desiree and Niels Ydes Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.