High recurrence rate of eczema herpeticum in moderate/severe atopic dermatitis –TREATgermany registry analysis

Traidl, Stephan; Heinrich, Luise; Siegels, Doreen; Rösner, Lennart; Haufe, Eva; Harder, Inken; Abraham, Susanne; Ertner, Konstantin; Kleinheinz, Andreas; Schäkel, Knut; Wollenberg, Andreas; Effendy, Isaak; Quist, Sven; Asmussen, Andrea; Wildberger, Julia; Weisshaar, Elke; Wiemers, Franka; Brücher, Jens‐Joachim; Weidinger, Stephan; Schmitt, Jochen; Werfel, Thomas; ,

doi:10.1111/ddg.15205

Cited by 5 publications

References 38 publications

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Identification and characterization of collagen XXIII alpha 1 as a novel risk factor for eczema herpeticum

Chopra,

Roesner,

Döhner

et al. 2024

Preprint

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BackgroundA subgroup of atopic dermatitis (AD) patients is prone to develop severe, disseminated cutaneous infection with herpes simplex virus (HSV), known as eczema herpeticum (EH). The occurrence of EH in a subset of AD patients and its frequent recurrence implies the importance of genetic factors in its pathogenesis.ObjectiveWe aimed to identify novel genetic risk factors for EH and study their impact on HSV-1 infection.MethodsWe performed whole exome sequencing on nine AD patients with (ADEH+) and without (ADEH-) a history of EH in comparison to healthy controls. We validated the finding of a variant of COL23A1 gene (encoding Collagen type XXIII alpha 1 chain) in ADEH in a larger cohort of 117 ADEH+, 117 ADEH-patients and 118 healthy controls by PCR. We studied the expression of COL23A1 in keratinocytes from ADEH+ and ADEH-patients, and the upregulated COL23A1 expression in primary keratinocytes and in the cell line HaCaT to study its role in HSV-1 infection.ResultsWe identified a single nucleotide polymorphism (SNP), rs2973744 inCOL23A1, as a risk factor for EH observed in 5% of ADEH+ patients, 1.6% of healthy donors and 0% of ADEH-patients. Primary human keratinocytes from an ADEH+ patient with SNP rs2973744 expressed higher COL23A1 levels and were more susceptible to HSV-1 than keratinocytes from ADEH-patients. In functional assays we showed that HSV-1 gene expression and cell-to-cell spread was more efficient in keratinocytes with increased expression of COL23A1. Moreover,COL23A1overexpression in HaCaT cells resulted in transcriptional downregulation of several genes that are involved in an effective immune response (IL1R1,IL32,TLR4,CFH,C3,S100A9,IRF1, andADAM23) and a notable upregulation ofTNCandSPINK5that are associated with AD.ConclusionUpregulation of COL23A1 promotes HSV-1 infection presumably by attenuating antiviral responses of keratinocytes. Among other markers, theCOL23A1SNP rs2973744 could be included in the screening of AD patients to identify patients at risk of EH, thus allowing early initiation of therapy.

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Identification and characterization of collagen XXIII alpha 1 as a novel risk factor for eczema herpeticum

Chopra,

Roesner,

Döhner

et al. 2024

Preprint

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Herpes Simplex Virus Assembly and Spread in murine skin after infection from the outside

Richardo,

Liu,

Döhner

et al. 2024

Preprint

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Herpes simplex viruses (HSV) cause many skin diseases, particularly in immunocompromised patients. HSV-1 infection of murine skin recapitulates many aspects of human pathology. However, many protocols rely on mechanical or enzymatic skin disruption to induce lesions, although this can alter skin homeostasis and prime antiviral inflammation before inoculation. To investigate the initial events following HSV-1 primary skin infection before the onset of symptoms, we developed a novel murine ex vivo explant model using gentle depilation but no further scarification and infected keratinocytes from the outside with minimal tissue damage. Two-photon microscopy studies showed that HSV-1 spread exclusively in the epidermis. The infection centers increased in number and size over time and contained hundreds of infected keratinocytes. We investigated the HSV-1 spread at the cellular level, using reporter strains with fluorescently-tagged capsid protein VP26, and monitored the formation of nuclear capsid assembly sites, nuclear capsid egress, and the recruitment of the inner tegument protein pUL37GFP, the outer tegument protein VP11/12GFP, and the envelope protein gDGFP to cytoplasmic capsids. By electron microscopy, the skin appeared intact, and keratinocytes contained many nuclear capsids, primary virions in the nuclear envelope, cytosolic membrane-associated capsids, and enveloped virions. Our protocol provides a robust and reproducible approach to investigate the very early events of HSV-1 spread in the skin, to characterize the phenotypes of HSV-1 mutants in terminally differentiated skin tissues, and to evaluate potentially antiviral small molecules in a preclinical ex vivo infection model.

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Neue Empfehlungen für die Versorgung von Patienten mit atopischer Dermatitis

Günther

2023

J Deutsche Derma Gesell

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High recurrence rate of eczema herpeticum in moderate/severe atopic dermatitis –TREATgermany registry analysis

Cited by 5 publications

References 38 publications

Identification and characterization of collagen XXIII alpha 1 as a novel risk factor for eczema herpeticum

Identification and characterization of collagen XXIII alpha 1 as a novel risk factor for eczema herpeticum

Herpes Simplex Virus Assembly and Spread in murine skin after infection from the outside

Neue Empfehlungen für die Versorgung von Patienten mit atopischer Dermatitis

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