Susceptibility to herpes simplex virus in atopic dermatitis

• Applicant: Dr. Stephan Traidl
• Subject Area: Clinical Immunology and Allergology ; Dermatology
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504117717

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The accompanied immunological changes are characterized by a type 2 dominated immune response. Viral infections are more prevalent in AD patients, especially in those with moderate to severe disease. A generalized infection with the herpes simplex virus (HSV), also known as eczema herpeticum (EH), is present in one in five patients of the AD registry TREATgermany. In 2017, dupilumab, a monocloncal antibody that targets the -subunit of the IL-4 and IL-13 receptor, was approved in Europe for the treatment of AD. Meta-analyses showed a reduced risk of EH under this targeted therapy. Previous work revealed an increased frequency of HSV-specific Th2 cells in patients with EH. However, in-depth studies regarding the alterations of innate as well as adaptive immune responses in AD patients with EH and the immunomodulatory influence of a blockade of the IL-4 and IL-13 receptor with regard to antiviral immune responses have not been performed so far.Therefore, this project aims to investigate the susceptibility of AD patients to viral infections and its modulation in the context of AD-specific therapeutic interventions. In patients with and without a history of EH, transcriptome analyses will be performed on skin and blood samples, and additional proteome analyses will be executed on serum samples. The analyses will focus on antiviral signaling pathways. In addition, imaging mass cytometry (IMC) will be used to compare acute EH lesions with genuine AD as well as non-EH HSV lesions. Furthermore, the transcriptome signatures of skin and blood under dupilumab therapy will be considered to identify therapy-dependent changes. Finally, HSV-specific T cells will be characterized from AD patients under dupilumab therapy, analyzing not only their polarization but also their cytokine profile.The identification of factors leadings to viral susceptibility in AD patients as well as the investigation of effects of targeted therapies, such as the IL-4/IL-13 receptor blocker dupilumab, may allow the detection of potentially beneficial or susceptibility-promoting effects on the viral defense and thereby contribute to the development of novel, patient-individualized systemic treatment regimes.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Thomas Werfel