AD endotypes evaluation with molecular-genetic analysis of local immune response



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Abstract

The basis for the development of atopic dermatitis (AD) is genetic predisposition, hypersensitivity to allergens, Th1/Th2 disbalance, increased degranulation of mast cells and antigen-presenting activity of Langerhans cells, as well as epidermal barrier dysfunction. Recently, genotypes, phenotypes and endotypes of AD, and biomarkers, which can be used to assess the effectiveness of therapy and to develop personalized approaches to the diagnosis, treatment and prognosis of the disease, have been actively studied. The aim of this study was to determine the endotypes of atopic dermatitis on the basis of molecular genetic study of cytokine gene expression in the skin of AD patients. Materials and methods. The study was performed as a «case-control», 90 AD patients and 30 healthy individuals without signs of atopy were included. The material for evaluation of cytokine gene expression was skin biopsy samples taken by punch biopsy. The level of gene expression was determined by real-time PCR with preliminary reverse transcription of mRNA of the corresponding genes («DNA-Technology», Moscow). The transcript levels of ILB, IL2, IL2r, IL4, IL5, IL6, IL7, IL8, IL10, IL12A, IL12B, IL15, IL17A, IL18, IL23, IL28, IL29, IFNy, TNF, TGFß, FOXP3 genes were studied. Results. Based on the molecular genetic study of the local immune response the following endotypes of AD were determined: endotype with predominance of Th1-type immune response (3% of patients); endotype with predominance of Th2-type immune response (3% of patients); mixed endotype with increased expression of IL2 (20% of patients); mixed endotype with reduced expression of IL10 (64% of patients); mixed endotype with increased expression of TGFß (9% of patients). Clinically significant biomarkers of inflammation in atopic dermatitis - decreased mRNA level of IL1ß gene expression and increased mRNA level of IL2R, IL4, IL5, IL6, IL8, IL10, IL12ß, IL23, IL29, IFNy and TGFß genes expression were determined in the skin of AD patients compared to healthy individuals. Conclusion. The use of molecular genetic method for evaluation of local immune response on the basis of cytokines gene expression measurement in the skin allows to identify the most significant biomarkers characterizing different endotypes of AD, and to determine the type of immune response in the individual patient.

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About the authors

O G Elisyutina

NRC Institute of Immunology FMBA of Russia

M N Boldyreva

NRC Institute of Immunology FMBA of Russia

O Yu Rebrova

Pirogov Russian National Research Medical University; National Research University Higher School of Economics

E S Fedenko

NRC Institute of Immunology FMBA of Russia

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