Baseline Skin Cytokine Profiles Determined By Rna In Situ Hybridization Correlate With Response To Dupilumab In Patients With Eczematous Dermatitis

Author

Katelyn SinghFollow

Date of Award

January 2023

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

William Damsky

Abstract

Dupilumab, a monoclonal antibody that inhibits IL4 and IL13, has revolutionized the treatment of atopic dermatitis (AD). However, not all patients respond optimally, and this may relate to underlying molecular heterogeneity. Yet, clinically useful and accessible methods to assess such heterogeneity have not been developed. Additionally, As the number of targeted medications continues to expand, the choice of which specific therapy to initiate in any individual patient will become increasingly difficult. Currently, there are no biomarkers that can be used to guide treatment selection in common inflammatory diseases such as atopic dermatitis (AD) and psoriasis. This study aims to determine whether cytokine staining and/or histologic features correlate with clinical response to dupilumab in patients with eczematous dermatitis. We retrospectively analyzed biopsies from 61 patients with eczematous dermatitis treated with dupilumab. RNA in situ hybridization (RISH) was used to measure markers of Type 2 (IL4, IL13), Type 1 (IFNG) and Type 3 (IL17A, IL17F, IL22) inflammation. Histologic features were also assessed. Patterns were compared among complete (n=16), partial (n=37), and non-responders (n=8) to dupilumab. We found that increased IL13 expression was associated with optimal response to dupilumab. In contrast, non-responders tended to express less IL13 and relatively greater levels of Type 1 and 3 cytokines. Histologically, non-responders tended to have increased levels of spongiosis, acanthosis, and epidermal inflammation. Overall, these findings suggest that cytokine profiles determined by RISH may aid in treatment selection for eczematous disorders and imply that tissue-based biomarkers may be useful in the personalization of the treatment of inflammatory skin disease.

Comments

This is an Open Access Thesis.

Recommended Citation

Singh, Katelyn, "Baseline Skin Cytokine Profiles Determined By Rna In Situ Hybridization Correlate With Response To Dupilumab In Patients With Eczematous Dermatitis" (2023). Yale Medicine Thesis Digital Library. 4197.
https://elischolar.library.yale.edu/ymtdl/4197