Dupilumab strengthens herpes simplex virus type 1-specific immune responses in atopic dermatitis.

Abstract

Impaired virus clearance in a subgroup of atopic dermatitis (AD) patients can lead to severe herpes simplex virus (HSV) infections called eczema herpeticum (EH). We recently identified a type 2 skewed viral immune response in EH patients. Clinical data suggest a reduced incidence of EH in AD patients treated with dupilumab, although immunologic investigations of this phenomenon are still lacking. We examined the impact of dupilumab on the HSV type 1 (HSV-1) specific immune response in AD, focusing on patients with (ADEH⁺) and without (ADEH^-) a history of EH. Sera and peripheral blood mononuclear cells were collected from ADEH⁺ and ADEH^- patients, a subgroup of whom was receiving dupilumab treatment, and healthy controls. Serum samples were tested for IgE against HSV-1 glycoprotein D (n = 85). Peripheral blood mononuclear cells were stimulated with HSV peptides, and activated CD4⁺ and CD8⁺ cells were characterized by flow cytometry after magnetic enrichment via CD154 or CD137 (n = 60). Cytokine production of HSV-1-reactive T-cell lines (n = 33) and MHC-I tetramer⁺ (HSV-1-UL25) CD8⁺ T cells was investigated by bead assay and intracellular cytokine staining (n = 21). We confirmed that HSV-1-specific IgE is elevated in ADEH⁺ patients. During dupilumab treatment, the IgE levels were significantly decreased, reaching levels of healthy controls. HSV-1-specific T_C1 frequencies were elevated in ADEH^- patients treated with dupilumab compared to dupilumab-negative patients. There were no changes in the frequencies of HSV-1-specific T_H cells while receiving dupilumab therapy. AD patients receiving dupilumab exhibited elevated IFN-γ and reduced IL-4 production in HSV-1-UL25-epitope-specific T cells compared to dupilumab-negative patients. Dupilumab may improve the HSV-1-specific immune response in AD as a result of an increased type I immune response and a reduction of HSV-1-specific IgE.