Abstract

Atopic dermatitis (AD) results from an overactive T helper 2 (Th2) immune response, while psoriasis is associated with Th17 immune polarization. AD and psoriasis are frequently treated with biologics which block the activity of key cytokines: IL-4, IL-13 and IL-12, IL-17, and IL-23, respectively. Presently, there are no commonly used biomarkers reflecting these underlying immune states that can be used to guide treatment selection, or to help with diagnosis in challenging cases. Here, we evaluate a chromogenic RNA in situ hybridization approach using commercially available probes for IL4, IL13 (and other AD cytokines) and IL12B (p40), IL17A/F, and IL23A (p19) (psoriasis cytokines) in a series of formalin fixed paraffin embedded skin biopsies from patients with AD (n=26), psoriasis (n=20) and healthy controls with clinically normal skin (n=10). Staining patterns were compared among the groups. We found that IL17A and IL13 staining patterns most readily distinguished cases of psoriasis from AD. 82% of AD cases showed staining for IL13. No cases of normal skin and only 18% of psoriasis cases had IL13 staining, which was focal and weak. 100% of the psoriasis cases showed IL17A expression, as opposed to only 4% of AD cases and 0% of normal skin cases. We also observed heterogeneity in the predominant cytokine expressed in any inidivual case within each diagnostic group with IL4, IL12B, IL17F, and IL23A staining patterns providing additional information. RNA in situ hybridization staining for pathogenic cytokines in AD and psoriasis occurred in the expected pattern and appears to be a robust approach. Intra-disease molecular heterogeneity was also observed. We envision several potential applications for this method and plan to evaluate whether molecular heterogeneity defined by this approach relates to response to cytokine targeting therapies.

Financial Disclosure: The oral presenter listed below disclosed the following information about their financial interests. The ASDP Ethics Committee has reviewed these disclosures and determined that no conflicts of interest exist between financial relationships and eeducational content being presented:

Speaker	Company	Affiliation/Relationship
William Damsky, MD, PhD	Eli Lilly Pfizer, Inc. TWi Biotechnology	Consultant Consultant, Conduct Research Consultant