Phosphodiesterase 4D, miR-203 and selected cytokines in the peripheral blood are associated with canine atopic dermatitis

Jeffrey Koury,Gagandeep Kaur,Ana Ramirez,Yvonne Drechsler,Tom Ramos,Chen Xie,Charli Dong,Chad Maki,Jijun Hao,Fari Izadyar,Jerry Harb,David Clark,Michel Simon

doi:10.1371/journal.pone.0218670

Abstract

Canine Atopic Dermatitis (AD) is a common complex and multifactorial disease involving immune dysregulation, genetic predisposition, skin barrier defects, environmental factors and allergic sensitization. To date, diagnosis of canine AD relies on a combination of patient history, clinical examination, allergy testing and response to diet trials/therapies with no reliable biomarkers available to distinguish AD from other diseases with similar clinical presentations. A handful of studies to identify potential biomarkers in the peripheral blood of AD dogs and healthy controls have been performed with some showing inconsistent and contradictory results. In this study, we, for the first time, report statistically significant increases in expression of phosphodiesterase 4D (PDE4D) gene in peripheral blood mononuclear cells (PBMCs) and miR-203 in plasma from AD dogs compared to healthy controls. In addition, we report a statistically non-significant change of the CD4+/CD8+ ratio, a dramatic decrease of three gene markers (PIAS1, RORA and SH2B1) as well as a panel of differential expression of cytokines in AD dogs in comparison to the healthy controls. Our study provides important insight into the complexities of canine AD, and further studies to verify the specificity of these findings for canine AD at a larger-scale are warranted.

Highlights

Canine atopic dermatitis (AD) is a common genetically predisposed inflammatory and pruritic allergic skin disorder in dogs worldwide [1]
Diagnosis of canine AD relies on a combination of patient history, clinical examination, allergy testing and response to diet trials/therapies, and no reliable biomarkers are available to distinguish canine AD from other presenting diseases such as food allergies, pyoderma, flea allergy dermatitis and malassezia dermatitis [10]
phosphodiesterase 4D (PDE4D) gene expression is significantly upregulated in AD dog peripheral blood mononuclear cells (PBMCs)

Summary

Introduction

Canine atopic dermatitis (AD) is a common genetically predisposed inflammatory and pruritic allergic skin disorder in dogs worldwide [1]. The pathogenesis remains elusive, epidermal barrier dysfunction and immune dysregulation following allergen exposure are believed to be implicated in the development of canine AD [2,3,4]. In canine AD, allergic skin inflammation is in part attributed to the diminished skin barrier function and the increased Type 2 Helper T (Th2) cell response. In the early acute phase, Th2 responses play predominant. Potential biomarkers for dogs with atopic dermatitis form of study reagents and were involved in study design and preparation of the manuscript

Methods

Results

Conclusion