Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals

Background. to comparatively investigate cytokine gene expression in the skin and peripheral blood of atopic dermatitis (AD) patients and healthy individuals. Methods. Samples of skin and peripheral blood from 48 severe AD patients SCORAD (Scoring Atopic Dermatitis) 78,5 [57; 89], IGA (Investigators Global Assessment) 4,2 [3,9; 4,7]) at the age of 17 to 45 years and 20 healthy donors aged from 19 to 32 years were analyzed for gene expression of cytokines using real time reverse transcription polymerase chain reaction (RT-PCR). Results. In the skin of patients with AD, a significant increase of the level of gene expression was observed for interleukin IL2R (interleukin) (р=0,0023), IL5 (р=0,002), IL6 (р=0,0023), IL8 (р=0,01), IL12β (р=0,0023), IL10 (р=0,0023), IL23 (р=0,002), IL29 (р=0,0023), and TGFβ (transforming growth factor) (p=0,0023) as compared to healthy individuals. In contrast, no difference between AD patients and healthy donors was detected with respect to cytokine gene expression in the peripheral blood. Conclusions. Activity of IL-2R, IL-8, IL-12β, IL-23, IL-29, and TGFβ that are markers of chronic inflammation and Th1 immune response in severe AD and IL-5, IL-10 that are anti-inflammatory cytokines and markers of Th2 response was predominant in the skin but not in the blood of AD patients.

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THE INFLUENCE OF TOPICAL GLUCOCORTICOSTEROIDS ONCYTOKINE GENE EXPRESSION IN THE SKIN AND PERIPHERALBLOOD OF ATOPIC DERMATITIS PATIENTS

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja779 ◽

2011 ◽

Vol 8 (3) ◽

pp. 19-30

Author(s):

Tat'yana Mikhaylovna Filimonova ◽

O G Elisyutina ◽

E S Fedenko ◽

O V Burmenskaya ◽

M N Boldyreva ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Atopic Dermatitis ◽

Proinflammatory Cytokines ◽

Peripheral Blood ◽

Mometasone Furoate ◽

Cytokine Gene Expression ◽

Immunological Study ◽

Cytokine Gene ◽

Foxp3 Gene

Background. To investigate the influence of mometasone furoate 0,1% cream on cytokine gene expression in the skin and peripheral blood of atopic dermatitis (AD) patients comparing with control. Material and methods. 40 AD patients were included in the study and divided into 2 groups. group 1 patients were given continuous course of mometasone furoate 0,1% cream treatment for 14 days. group 2 patients were given indifferent emollient elobase cream for 14 days. Clinical efficacy of the treatment was assessed on the following features: SCORAD index, Investigators global Assessment (IgA) score and subjective assessment of itch and dryness of the skin according to skin area to be studied. Skin samples and peripheral blood of atopic dermatitis were used as material for immunological study. Interleukin (IL)1B, IL2, IL2r, IL4, IL5, IL6, IL7, IL8, IL10, IL 12A, IL12B, IL15 (total), IL15 , IL17A, IL18, IL23, IL28, IL29, Interferon (IFN)-, Tumor necrosis factor (TNF), Transforming growth factor beta 1 (TGFB1), forkhead box P3 (FOXP3) gene expression were defined in the skin and peripheral blood of AD patients by realtime reverse transcription polymerase chain reaction (RT-pCR). Results. positive clinical effect was found with all AD patients on the mometasone furoate 0,1% cream therapy background for 14 days and also dryness, rushes and skin itch decreased. Stаtistical significant decrease of proinflammatory cytokines IL2, IL2r, IL5, IL8, IL12В, IL23, IFN- gene expression was marked. They are the markers of chronic inflammation and Th1 immune response. Studying peripheral blood after mometasone furoate 0,1% cream treatment increase of TGFB1, FOXP3 gene expression level was found. no significant changes of cytokine gene expression in AD patients, who got elobase cream were found. Conclusion. Antiinflammatory activity of mometasone furoate 0,1% cream was shown by its influence on proinflammatory cytokines IL2, IL2r, IL5, IL8, IL12В, IL23, IFN- gene expression in the skin and mechanisms of immune response in moderate and severe AD patients.

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

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja100 ◽

2018 ◽

Vol 15 (6) ◽

pp. 33-44

Author(s):

O G Elisyutina ◽

M N Boldyreva ◽

O Yu Rebrova ◽

E S Fedenko

Keyword(s):

Gene Expression ◽

Immune Response ◽

Atopic Dermatitis ◽

Mrna Level ◽

Molecular Genetic ◽

Cytokine Gene Expression ◽

Local Immune Response ◽

Cytokine Gene ◽

Healthy Individuals ◽

Molecular Genetic Study

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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