IL-4Ra (Generian)

Targeting the interleukin-4 receptor alpha (IL-4Rα) subunit has proven clinical efficacy in atopic dermatitis (AD).

This study assessed the peripheral phenotype and function of T-cells, but also levels of total and sIgE and its receptors in AD patients receiving dupilumab.

AD patients were clinically assessed (n = 75) and peripheral blood samples were taken (n = 25). Multiparametric flow cytometry was performed to characterize T-cell subsets (before treatment and 6 months later). Total and specific IgE were measured by ImmunoCap, soluble CD23 and FcεR1 in serum by ELISA, and eosinophils by differential blood analysis.

SCORing Atopic Dermatitis scores and body surface area involvement decreased upon treatment after 6 months of treatment to 67% and 77% from baseline. At the T cell level, we observed a 0.55-fold reduction of Th2-cells and a mean 27% increase in regulatory T-cells from baseline, accompanied by shifts towards Th1 and Th17 phenotypes. Furthermore, circulating CD4⁺CXCR5⁺TFH17 and CD4⁺CXCR5⁺TFH17.1 positive cells (mean 40% and 42%) and T-cell-specific IL-2 (+0.96-fold) and IL-10 (+1.96-fold) secretion increased, whereas IL-4 (mean -55%) and IL-17A (mean -27%) were reduced. Eosinophil counts (mean -22%), total IgE (mean -47%) and House Dust Mite sIgE (mean -40%) decreased, whereas CD23 and FcεR1 remained unchanged.

The T-cell and cytokine profiles during anti-IL4-Ra treatment suggest that targeting this pathway promotes a systemic shift of the T-cell compartment by reducing the T helper type 2 and complementary IgE responses. The sustainability of these disease-modifying effects requires further investigation.