Topographic Expression of IL-1β and Inflammasome-Associated Proteins in Lesional, Perilesional, and Distant Hidradenitis Suppurativa Skin
5 affiliations
- 1Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdansk, Smoluchowskiego 17 Street, 80-214 Gdansk, Poland
- 2Department of Dermatology, Venereology and Allergology, University Clinical Centre in Gdansk, Dębinki 7 Street, 80-952 Gdansk, Poland
- 3Department of Medical Chemistry, Medical University of Gdansk, Debinki 1 Street, 80-211 Gdansk, Poland
- 4Department of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, 70569 Stuttgart, Germany
- 5Euro-Mediterranean Institute of Science and Technology, 90139 Palermo, Italy
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, draining tunnels, and scarring. Dysregulated IL-1 and inflammasome-associated pathways have been implicated in its pathogenesis, but their spatial distribution beyond clinically apparent lesions remains incompletely characterized. To assess topographic expression of NLRP3, caspase-1, IL-1β, and IL-18 across lesional, perilesional, and distant HS skin. Skin samples were obtained from eight biologic-untreated patients with HS, six patients receiving adalimumab, and five healthy controls. In HS, matched 6 mm full-thickness biopsies were obtained from the same axilla at an active inflammatory lesion (0 cm), clinically normal-appearing skin 2 cm from the visible lesion edge, and clinically uninvolved skin 10 cm from the lesion edge. Protein abundance was assessed by Western blot. Primary topographic effects were evaluated using mixed-design ANOVA with Benjamini–Hochberg FDR correction, supplemented by non-parametric and exploratory contrast analyses. No protein showed an FDR (false discovery rate)-significant overall site effect or cohort × site interaction in the primary analysis. In biologic-untreated HS, IL-18 showed an FDR-significant topographic effect (q = 0.0444), with higher expression at 0 cm than at 10 cm (q = 0.0469). An exploratory post hoc 2-versus-10 cm analysis identified a highly concordant IL-1β pattern: expression was higher at 2 cm in 7/8 biologic-untreated and 6/6 adalimumab-treated patients. Fisher’s combined probability remained significant after BH correction across the four proteins evaluated for this contrast (p = 0.00421, q4 = 0.0168), whereas comprehensive correction across all 12 protein × contrast combinations yielded q12 = 0.0505 and did not meet q < 0.05. Overall, 13/14 patients showed the same direction (92.9%; exact 95% CI 66.1–99.8%). IL-18 provided the clearest FDR-supported secondary topographic finding. IL-1β showed a highly concordant but hypothesis-generating perilesional-to-distant spatial pattern, whereas total NLRP3 and caspase-1 did not show robust FDR-adjusted spatial variation.
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BibTeX
@article{lewandowski2026topographic,
title = {{Topographic Expression of IL-1β and Inflammasome-Associated Proteins in Lesional, Perilesional, and Distant Hidradenitis Suppurativa Skin}},
author = {Miłosz Lewandowski and Magdalena Górska-Ponikowska and Anna Jakubczyk-Słabicka and Zuzanna Świerczewska and Wioletta Barańska-Rybak},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209085},
url = {https://www.mdpi.com/1422-0067/27/20/9085},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Topographic Expression of IL-1β and Inflammasome-Associated Proteins in Lesional, Perilesional, and Distant Hidradenitis Suppurativa Skin
AU - Miłosz Lewandowski
AU - Magdalena Górska-Ponikowska
AU - Anna Jakubczyk-Słabicka
AU - Zuzanna Świerczewska
AU - Wioletta Barańska-Rybak
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209085
UR - https://www.mdpi.com/1422-0067/27/20/9085
AB - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, draining tunnels, and scarring. Dysregulated IL-1 and inflammasome-associated pathways have been implicated in its pathogenesis, but their spatial distribution beyond clinically apparent lesions remains incompletely characterized. To assess topographic expression of NLRP3, caspase-1, IL-1β, and IL-18 across lesional, perilesional, and distant HS skin. Skin samples were obtained from eight biologic-untreated patients with HS, six patients receiving adalimumab, and five healthy controls. In HS, matched 6 mm full-thickness biopsies were obtained from the same axilla at an active inflammatory lesion (0 cm), clinically normal-appearing skin 2 cm from the visible lesion edge, and clinically uninvolved skin 10 cm from the lesion edge. Protein abundance was assessed by Western blot. Primary topographic effects were evaluated using mixed-design ANOVA with Benjamini–Hochberg FDR correction, supplemented by non-parametric and exploratory contrast analyses. No protein showed an FDR (false discovery rate)-significant overall site effect or cohort × site interaction in the primary analysis. In biologic-untreated HS, IL-18 showed an FDR-significant topographic effect (q = 0.0444), with higher expression at 0 cm than at 10 cm (q = 0.0469). An exploratory post hoc 2-versus-10 cm analysis identified a highly concordant IL-1β pattern: expression was higher at 2 cm in 7/8 biologic-untreated and 6/6 adalimumab-treated patients. Fisher’s combined probability remained significant after BH correction across the four proteins evaluated for this contrast (p = 0.00421, q4 = 0.0168), whereas comprehensive correction across all 12 protein × contrast combinations yielded q12 = 0.0505 and did not meet q < 0.05. Overall, 13/14 patients showed the same direction (92.9%; exact 95% CI 66.1–99.8%). IL-18 provided the clearest FDR-supported secondary topographic finding. IL-1β showed a highly concordant but hypothesis-generating perilesional-to-distant spatial pattern, whereas total NLRP3 and caspase-1 did not show robust FDR-adjusted spatial variation.
SN - 1422-0067
ER -