Superficial Conjunctival Cells from Dupilumab-Treated Patients with Atopic Dermatitis with Ocular Adverse Events...

Area of Science:

• Ophthalmology
• Dermatology
• Genomics

Background:

• Dupilumab is effective for atopic dermatitis.
• Ocular adverse events (OAEs) like conjunctivitis and dry eye occur in some patients treated with dupilumab.
• The underlying pathological mechanisms for these OAEs remain unclear.

Purpose of the Study:

• To investigate the conjunctival transcriptome of atopic dermatitis patients before and after dupilumab treatment.
• To identify differences in gene expression between patients who develop OAEs and those who do not.
• To explore potential predisposing factors for dupilumab-induced OAEs.

Main Methods:

• A bicentric study involving 36 atopic dermatitis patients.
• DNA microarray analysis of conjunctival cells obtained via impression cytology.
• Comparison of gene expression profiles at baseline (M0) and 4 months post-treatment (M4).
• Division of patients into OAE+ (n=12) and OAE- (n=24) groups based on ophthalmological status at M4.
• Ingenuity Pathway Analysis and real-time RT-PCR for validation.

Main Results:

• Significant differences in gene expression were observed between OAE+ and OAE- groups at both M0 (52 genes) and M4 (113 genes).
• A psoriasis signature was identified in OAE+ patients, both before and after treatment.
• Overexpression of genes related to keratinocyte differentiation and cornified envelope components was noted in OAE+ patients.
• Real-time RT-PCR confirmed upregulation of 9 genes and downregulation of MUC7 in OAE+ patients at M4.

Conclusions:

• Conjunctival gene expression profiles may predispose atopic dermatitis patients to developing OAEs during dupilumab therapy.
• The identified psoriasis signature and altered keratinocyte differentiation pathways offer insights into OAE pathogenesis.
• Further research is warranted to elucidate the precise mechanisms and develop targeted preventive strategies.