IL-36–driven pustulosis: Transcriptomic signatures match between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) - 04/06/25

Doi : 10.1016/j.jaci.2025.01.046

Theresa Benezeder, PhD ^a, Natalie Bordag, PhD ^a, Johannes Woltsche, MD ^a, Katharina Falkensteiner, MD ^a, Thomas Graier, MD, PhD ^a, Eva Schadelbauer, MD ^a, Lorenzo Cerroni, MD ^a, Damian Meyersburg, MD ^b, Valeria Mateeva, MD ^c, Adam Reich, MD ^d, Marta Kołt-Kamińska, MD ^d, Gudrun Ratzinger, MD ^e, Julia-Tatjana Maul, MD ^f,^g, Barbara Meier-Schiesser, MD, PhD ^f,^g, Alexander A. Navarini, MD ^h, Romana Ceovic, MD ⁱ, Knut Prillinger, MD ^j, Maruska Marovt, MD ^k, Lev Pavlovksy, MD, PhD ^l, Andrea Szegedi, MD ^m, Maria Sanzharovskaja, PhD ⁿ, Herwig Zach, PhD ⁿ, Peter Wolf, MD ^a,^⁎
^a Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
^b Department of Dermatology and Allergology, University Hospital Salzburg of the Paracelsus Medical University, Salzburg, Austria
^c Department of Dermatology and Venereology, Medical Faculty, Medical University, Sofia, Bulgaria
^d Department of Dermatology, Faculty of Medicine, Medical College of Rzeszów University, Rzeszów, Poland
^e Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria
^f Department of Dermatology, University of Zürich, Zürich, Switzerland
^g Faculty of Medicine, University of Zürich, Zürich, Switzerland
^h Department of Dermatology, University Hospital Basel, Basel, Switzerland
ⁱ Department of Dermatology and Venereology, School of Medicine University of Zagreb, University Hospital Centre Zagreb, Zagreb, Croatia
^j Department of Dermatology, University Hospital St Pölten, St Pölten, Austria
^k Department of Dermatology, University Medical Centre Maribor, Maribor, Slovenia
^l Division of Dermatology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel
^m Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
ⁿ Boehringer Ingelheim RCV, Vienna, Austria

^∗Corresponding author: Peter Wolf, MD, Department of Dermatology and Venereology, Medical University of Graz, Auenbruggerplatz 8, 8036 Graz, Austria.Department of Dermatology and VenereologyMedical University of GrazAuenbruggerplatz 8Graz8036Austria

Graphical abstract

Le texte complet de cet article est disponible en PDF.

Abstract

Background

Due to similarities, the distinction between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) has been a matter of debate for a long time.

Objectives

Our aim was to define the molecular features of GPP and AGEP.

Methods

We analyzed skin biopsy samples and clinical data from 125 patients with AGEP, GPP, palmoplantar pustulosis (PPP), plaque psoriasis (PSO), and nonpustular cutaneous adverse drug reactions (ADRs), as well as from healthy skin controls using RNA-sequencing and blinded histopathologic analyses.

Results

The transcriptome and histopathologic features of AGEP and GPP samples exhibited significant overlap (177 differentially expressed genes [DEGs] in GPP and AGEP compared to healthy skin, only 2 DEGs comparing AGEP and GPP). Yet, they displayed marked differences from those of PPP, PSO, and ADR samples, with a notable number of DEGs (131 DEGs comparing AGEP and PSO, 75 DEGs comparing AGEP and PPP, and 52 DEGs comparing AGEP and ADR). A transcriptome profile subgroup evaluation of >13,000 analyzed genes did not reveal any DEGs in drug-induced GPP and AGEP. Moreover, the immune response pattern and immune cell composition did not differ between drug-induced GPP and AGEP, whereas non–drug-induced GPP had higher expression of T_H17-cell–related genes and a higher neutrophil count than AGEP.

Conclusions

We propose that AGEP is a drug-induced variant of GPP and therefore part of IL-36–related pustulosis. A key signature overarching this spectrum was identified, thereby opening the therapeutic approach of IL-36 inhibition to all subtypes of the disease.

Le texte complet de cet article est disponible en PDF.

Key words : IL36, acute generalized exanthematous pustulosis, AGEP, generalized pustular psoriasis, GPP, palmoplantar pustulosis, PPP, plaque psoriasis, cutaneous adverse drug reactions

Abbreviations used : ADR, AGEP, DEGs, FFPE, GPP, HCO, IL36R, NK, PCA, PPP, PSO, RNA-seq

Plan

Methods

Patients and biopsy samples

Histopathologic analyses

RNA extraction, sequencing, and data analysis

Results

Study population

Histopathologic patterns of AGEP and GPP

Transcriptomic profiles of AGEP and GPP

Immune response pattern genes and anti-IL-36R responder genes in AGEP and GPP

Immune cell composition patterns in AGEP and GPP

Discussion

Conclusion

Export

Vol 155 - N° 6

P. 1913-1927 - juin 2025 Retour au numéro

Article précédent

Psoriasis harbors multiple pathogenic type 17 T-cell subsets: Selective modulation by risankizumab
Jaehwan Kim, Jongmi Lee, Jongeun Lee, Katherine Kim, Xuan Li, Wei Zhou, Junyue Cao, James G. Krueger

| Article suivant

Basophil-VAMP7 is a vital regulator of skin barrier integrity and chronic itch
Wenhao Zhang, Xiaolong Dai, Weiwei Chen, Yanqing Li, Huiyuan Mei, Jorg Buddenkotte, Xingyun Zhu, Martin Steinhoff, Jiafu Wang, Jianghui Meng

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

IL-36–driven pustulosis: Transcriptomic signatures match between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) - 04/06/25

Graphical abstract

Abstract

Background

Objectives

Methods

Results

Conclusions

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL