Secukinumab and Dead Sea Climatotherapy Impact Resolved Psoriasis Skin Differently Potentially Affecting Disease Memory

Thomas Emmanuel*, Borislav Ignatov, Trine Bertelsen, Thomas Litman, Morten Muhlig Nielsen, Mikkel Bo Brent, Toke Touborg, Anders Benjamin Rønsholdt, Annita Petersen, Mette Boye, Ida Kaaber, Daniel Sortebech, Dorte Lybæk, Torben Steiniche, Anne Bregnhøj, Liv Eidsmo, Lars Iversen, Claus Johansen

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory.

Original languageEnglish
Article number6086
JournalInternational Journal of Molecular Sciences
Volume25
Issue11
Number of pages18
ISSN1661-6596
DOIs
Publication statusPublished - Jun 2024

Keywords

  • T lymphocytes
  • biologics
  • inflammatory skin diseases
  • phototherapy
  • psoriasis
  • tissue resident memory T-cells

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