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

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.

scholarly journals Local and systemic immune response in patients withsevere atopic dermatitis

2011 ◽  
Vol 8 (5) ◽  
pp. 10-15
Author(s):  
T M Filimonova ◽  
Ol'ga Gur'evna Elisyutina ◽  
E S Fedenko ◽  
D D Niyazov ◽  
M N Boldyreva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Atopic Dermatitis ◽  
Peripheral Blood ◽  
Transforming Growth Factor ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Healthy Individuals ◽  
Th2 Response ◽  
Healthy Donors

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.

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

Self/Nonself ◽  
2011 ◽  
Vol 2 (2) ◽  
pp. 120-124 ◽  
Author(s):  
Elena S. Fedenko ◽  
Olga G. Elisyutina ◽  
Tatiana M. Filimonova ◽  
Margarita N. Boldyreva ◽  
O. V. Burmenskaya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atopic Dermatitis ◽  
Peripheral Blood ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Healthy Individuals

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

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)-ƒ, 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-ƒ 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-ƒ gene expression in the skin and mechanisms of immune response in moderate and severe AD patients.

Suppression of cytokine gene expression and improved therapeutic efficacy of microemulsion-based tacrolimus cream for atopic dermatitis

2012 ◽  
Vol 2 (2) ◽  
pp. 129-141 ◽  
Author(s):  
Manisha S. Lalan ◽  
Naresh C. Laddha ◽  
Jigar Lalani ◽  
Muhammad J. Imran ◽  
Rasheedunnisa Begum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atopic Dermatitis ◽  
Therapeutic Efficacy ◽  
Cytokine Gene Expression ◽  
Cytokine Gene

scholarly journals Influence of topical immunosuppressive therapy with tacrolimus on local immune response in skin of atopic dermatitis patients

2017 ◽  
Vol 14 (3) ◽  
pp. 27-34
Author(s):  
O G Elisyutina ◽  
E S Fedenko ◽  
M N Boldyreva ◽  
V V Kadochnikova
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Atopic Dermatitis ◽  
Clinical Efficacy ◽  
Skin Lesions ◽  
Severe Atopic Dermatitis ◽  
Local Immune Response ◽  
Topical Tacrolimus ◽  
Immune Parameters ◽  
Before And After

Background. To study tacrolimus 0,1% ointment influence on the skin local immune parameters in patients with moderate and severe atopic dermatitis (AD). Materials and methods. The study included 30 patients with moderate (n=20) and severe (n=10) AD. All patients underwent a topical continuous course of treatment with tacrolimus 0,1% ointment twice a day for 14 days. The clinical efficacy of tacrolimus 0,1% ointment was evaluated by the change of the following parameters: SCORAD index, Investigator Global Assessment (IGA) before and after the treatment. All patients underwent a study of local immune response before and after the treatment with the assessment of the expression of IL4, IL5, IL7, IL8, IL10, IL17A, IL23, IL23, IFNγ TGFB1, FOXP3 genes in irritated and treated skin lesions obtained by biopsy. Results. Positive clinical effect - reduction of infiltration, papular rash, dryness, intensity of itch, reflected in the significant decreasing of SCORAD index and IGA was found. The significant decreasing of TGFß (p=0,043308) and IL8 (p=0,038867) gene expression level was revealed, TGFβ and IL8 are the markers of chronic inflammation in atopic dermatitis. The decrease of these parameters during the topical tacrolimus treatment demonstrates local immune response changes in the skin, accompanied by improvement of AD symptoms. Conclusion. The study showed clinical efficacy as well as immunosuppressive activity of tacrolimus 0,1% ointment in patients with moderate and severe AD represented in decreasing of proinflammatory cytokines gene expression TGFβ and IL8 in skin lesions.

scholarly journals Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares

2010 ◽  
Vol 299 (3) ◽  
pp. L374-L383 ◽  
Author(s):  
Ning Li ◽  
Jack R. Harkema ◽  
Ryan P. Lewandowski ◽  
Meiying Wang ◽  
Lori A. Bramble ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Airway Inflammation ◽  
Ultrafine Particles ◽  
Allergic Airway Inflammation ◽  
Cytokine Gene Expression ◽  
Secondary Immune Response ◽  
Cytokine Gene ◽  
Adjuvant Effect ◽  
Traffic Exposure

We have previously demonstrated that intranasal administration of ambient ultrafine particles (UFP) acts as an adjuvant for primary allergic sensitization to ovalbumin (OVA) in Balb/c mice. It is important to find out whether inhaled UFP exert the same effect on the secondary immune response as a way of explaining asthma flares in already-sensitized individuals due to traffic exposure near a freeway. The objective of this study is to determine whether inhalation exposure to ambient UFP near an urban freeway could enhance the secondary immune response to OVA in already-sensitized mice. Prior OVA-sensitized animals were exposed to concentrated ambient UFP at the time of secondary OVA challenge in our mobile animal laboratory in Los Angeles. OVA-specific antibody production, airway morphometry, allergic airway inflammation, cytokine gene expression, and oxidative stress marker were assessed. As few as five ambient UFP exposures were sufficient to promote the OVA recall immune response, including generating allergic airway inflammation in smaller and more distal airways compared with the adjuvant effect of intranasally instilled UFP on the primary immune response. The secondary immune response was characterized by the T helper 2 and IL-17 cytokine gene expression in the lung. In summary, our results demonstrated that inhalation of prooxidative ambient UFP could effectively boost the secondary immune response to an experimental allergen, indicating that vehicular traffic exposure could exacerbate allergic inflammation in already-sensitized subjects.

scholarly journals Cytokine gene regulation by PGE2, LTB4and PAF

1992 ◽  
Vol 1 (1) ◽  
pp. 5-8 ◽  
Author(s):  
M. Rola-Pleszczynski ◽  
J. Stankova
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Gene Regulation ◽  
Inflammatory Response ◽  
Cytokine Production ◽  
Initial Response ◽  
Lipid Mediators ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Regulatory Effects

The initial response of the host to noxious stimuli produces a nonspecific inflammatory response. A more specific immune response is believed to be modulated by two classes of molecules: lipid mediators (PG, LT and PAF) and cytokines, synthesized by phagocytes and parenchyreal cells. In this review we discuss the increasing evidence of the interrelationship between eicosanoids, PAF and cytokines: IL-1 and TNF induce PG synthesis in various cells and PG, in turn, modulate cytokine production. We focused on the regulatory effects ofLTB4,PGE2and PAF on cytokine gene expression.

Sign in / Sign up

Export Citation Format

Share Document