Blood Single-Cell Transcriptomic and Proteomic Signatures of Paradoxical Eczema in Patients with Psoriasis Treated with Biologics
Biologics targeting the TNF and IL-17/23 axis are highly effective treatments for psoriasis but can result in cutaneous adverse events. The pathogenesis of paradoxical eczema, the occurrence of an atopic dermatitis phenotype after biologic initiation in people with psoriasis, is unknown. Using single-cell RNA sequencing and mass cytometry, we found increased expression of TNF, IFN-γ, and IFN-α and their signaling pathways in paradoxical eczema case cell clusters compared with that in matched psoriasis controls. Genetic variants influencing the expression of chemokine signaling and TNF pathway genes were associated with paradoxical eczema in a separate genotyped cohort, and this association was independent of known atopic risk loci. This suggests that paradoxical eczema has a predominantly type 1 systemic inflammatory signature and that genetic susceptibility to aberrant chemokine and TNF pathway signaling could contribute to development of this phenotype during biologic treatment.
Authors
- Ali Al‐Janabi (ORCID: https://orcid.org/0000-0002-2094-0556)
- Christopher Em Griffiths
- Anne C Barton (ORCID: https://orcid.org/0000-0003-3316-2527)
- Andrew Skelton (ORCID: https://orcid.org/0000-0002-1094-6217)
- Amy Foulkes (ORCID: https://orcid.org/0000-0003-2680-750X)
- Stephen Eyre (ORCID: https://orcid.org/0000-0002-1251-6974)
- Hefin Rhys (ORCID: https://orcid.org/0000-0002-7385-9014)
- Sébastien Viatte (ORCID: https://orcid.org/0000-0001-6471-3358)
- Richard Bruce Warren (ORCID: https://orcid.org/0000-0002-2918-6481)
- Catherine Smith (ORCID: https://orcid.org/0000-0001-9918-1144)
- Maria Christofi
- Andrew P. Morris (ORCID: https://orcid.org/0000-0002-6805-6014)
- Adnan R. Khan (ORCID: https://orcid.org/0000-0001-7126-7157)
- Paul Martin (ORCID: https://orcid.org/0000-0002-1016-6851)
- Catherine Simpson
Institutions
- Guy's and St Thomas' NHS Foundation Trust (GB)
- Manchester Academic Health Science Centre (GB)
- University of Manchester (GB)
- King's College Hospital NHS Foundation Trust (GB)
- Arthritis UK (GB)
- UCB Pharma (United Kingdom) (GB)
- NIHR Manchester Biomedical Research Centre (GB)
Publication Details
- Journal
- Journal of Investigative Dermatology
- Published
- 2025-03-29
- DOI
- https://doi.org/10.1016/j.jid.2025.02.153
- Citations
- 6
- Primary Topic
- Psoriasis: Treatment and Pathogenesis
- Type
- article
- Field-Weighted Citation Impact
- 4.78