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

Stephan Traidl; Leonard Harries; Petra Kienlin; Gabriele Begemann; Lennart M Roesner; Thomas Werfel

doi:10.1016/j.jaci.2023.08.024

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

J Allergy Clin Immunol. 2023 Dec;152(6):1460-1469.e5. doi: 10.1016/j.jaci.2023.08.024. Epub 2023 Sep 1.

Authors

Stephan Traidl¹, Leonard Harries², Petra Kienlin², Gabriele Begemann², Lennart M Roesner³, Thomas Werfel³

Affiliations

¹ Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany. Electronic address: traidl.stephan@mh-hannover.de.
² Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
³ Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.

PMID: 37660986
DOI: 10.1016/j.jaci.2023.08.024

Abstract

Background: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: Atopic dermatitis; dupilumab; eczema herpeticum; herpes simplex virus type 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Cytokines
Dermatitis, Atopic*
Herpesvirus 1, Human*
Humans
Immunity
Immunoglobulin E
Kaposi Varicelliform Eruption*
Leukocytes, Mononuclear

Substances

dupilumab
Cytokines
Immunoglobulin E