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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-Burri, Denise C; Simon, Hans-Uwe; Simon, Dagmar.
Afiliação
  • Thormann K; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Lüthi AS; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Deniau F; Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Heider A; Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland.
  • Cazzaniga S; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Radonjic-Hoesli S; Centro Studi GISED, Bergamo, Italy.
  • Lehmann M; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Schlapbach C; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Herzog EL; Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Kreuzer M; Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Zinkernagel MS; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Akdis CA; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
  • Zysset-Burri DC; Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, Bern, Switzerland.
  • Simon HU; Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Simon D; Department for BioMedical Research, University of Bern, Bern, Switzerland.
Allergy ; 79(4): 937-948, 2024 04.
Article em En | MEDLINE | ID: mdl-38317432
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dermatite Atópica / Oftalmopatias / Anticorpos Monoclonais Humanizados Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dermatite Atópica / Oftalmopatias / Anticorpos Monoclonais Humanizados Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article