Dupilumab-associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation.

Thormann, Kathrin; Lüthi, Anne-Sophie; Deniau, Felix; Heider, Anja; Cazzaniga, Simone; Radonjic-Hoesli, Susanne; Lehmann, Mathias; Schlapbach, Christoph; Herzog, Elio L; Kreuzer, Marco; Zinkernagel, Martin S; Akdis, Cezmi A; Zysset, Denise C; Simon, Hans-Uwe; Simon, Dagmar (2024). Dupilumab-associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation. Allergy, 79(4), pp. 937-948. Wiley-Blackwell 10.1111/all.16045

Allergy_-_2024_-_Thormann_-_Dupilumab_associated_ocular_surface_disease_is_characterized_by_a_shift_from_Th2_Th17_toward.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (5MB) | Preview


Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy.


Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non-AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology.


Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL-12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non-AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome.


DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde
08 Faculty of Science > Department of Biology > Bioinformatics and Computational Biology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Cazzaniga, Simone, Radonjic, Susanne Irene, Lehmann, Mathias, Schlapbach, Christoph, Herzog, Elio Luca, Kreuzer, Marco Claudio, Zinkernagel, Martin Sebastian, Zysset, Denise Corinne, Simon, Hans-Uwe, Simon, Dagmar


600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture








Pubmed Import

Date Deposited:

07 Feb 2024 08:35

Last Modified:

01 Apr 2024 00:14

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

atopic dermatitis dry eye disease dupilumab ocular surface disease remodeling type 1 inflammation





Actions (login required)

Edit item Edit item
Provide Feedback