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 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 P014 Identification of Crohn’s disease immunopathotypes

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
H M Baer ◽  
E MacDonald ◽  
A Ferguson ◽  
A M Scott ◽  
M I Khan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Local Immune Response ◽  
Cross Sectional ◽  
Treatment Responses ◽  
Colonic Biopsies

Abstract Background Crohn’s disease (CD) is a chronic inflammatory gastrointestinal condition, with globally increasing incidence. Patients with CD suffer from a loss of tolerance towards their commensal microbiota causing an aberrant immune response, occurring in a protracted relapse and remission cycle. Although a variety of frontline therapies is currently available, including targeted therapies such as biologic drugs, 30–40% of CD patients still require surgery to manage the disease. At present, the immunobiology of CD is not fully understood. However, differences in immune responses between patients might play an important role in diverse treatment responses. The aim of this study was to identify differences in peripheral and local immune responses of CD to understand differences in disease behaviour and treatment outcome. Methods Peripheral blood mononuclear cells and plasma were isolated from whole blood of a cross-sectional CD patient cohort (nCD = 12) and normal controls (NC, nNC = 28). Flow cytometry analysis and multiplex assays were used to quantify immune cell populations and cytokine levels, respectively. The local immune response was analysed by bulk RNA sequencing of mucosal colonic biopsies either from inflamed CD or normal tissue. Gene signatures were then followed up by validation in publicly deposited gene expression datasets (nCD = 36, nNC = 24), and by measurement of specific proteins using our archived samples. Results Peripheral immunophenotyping of the initial cross-sectional study displayed three different types of CD patients, characterised by either a decrease in leukocyte populations, an increase of cytokines, or a change in both. Analysis of the RNAseq data derived from colonic biopsies revealed four distinct clusters in genes associated with the immune response in CD patients. Further pathway analysis showed one cluster with an enriched B cell signature and another cluster with an elevated macrophage and neutrophil response. We utilised publicly available gene expression datasets to validate these signatures in a larger cohort and identified a selection of patients with an up-regulated pro-inflammatory macrophage response. Using correlation analysis, we suggest an immunopathotype with increased macrophage activation which is potentially associated with a more severe form of the disease. Conclusion We have identified distinct immunopathotypes in both the peripheral and local immune response of CD patients. Further investigation will correlate these distinct immune responses in CD with clinical parameters, to understand associations between diverse treatment responses and disease behaviours.

scholarly journals Successful Treatment of Severe Atopic Dermatitis with Calcitriol and Paricalcitol in an 8-Year-Old Girl

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Christina Bothou ◽  
Alexis Alexopoulos ◽  
Eleni Dermitzaki ◽  
Kleanthis Kleanthous ◽  
Anastasios Papadimitriou ◽  
...  
Keyword(s):  
Vitamin D ◽  
Atopic Dermatitis ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Vitamin D Supplementation ◽  
Severe Atopic Dermatitis ◽  
Efficacious Treatment ◽  
Children And Adolescence ◽  
Therapy Treatment

Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement—almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.

Clinical efficacy of neural therapy for the treatment of atopic dermatitis in dogs

2008 ◽  
Vol 56 (4) ◽  
pp. 459-469 ◽  
Author(s):  
Adriana Bravo-Monsalvo ◽  
Juan Vázquez-Chagoyán ◽  
Lilia Gutiérrez ◽  
Héctor Sumano
Keyword(s):  
Atopic Dermatitis ◽  
Clinical Efficacy ◽  
Severity Index ◽  
Control Group ◽  
Matched Pairs ◽  
Neural Therapy ◽  
Canine Atopic Dermatitis ◽  
Dermatological Condition ◽  
Before And After ◽  
History Of

The aim of this trial was to assess the clinical efficacy of neural therapy (NT) when treating canine atopic dermatitis. Eighteen dogs (no control group), with at least a 12-month history of having nonseasonal atopic dermatitis, were included. No medication with either glucocorticoids or cyclosporin was allowed during the trial. One set of NT was given by injecting an intravenous dose of 0.1 mg/kg of a 0.7% procaine solution, followed by 10 to 25 intradermal injections of the same solution in a volume of 0.1–0.3 mL per site. Dogs were given 6–13 sets of NT during the therapy. The dermatological condition of each patient was evaluated before and after the treatment using two scales: the pruritus visual analogue scale (PVAS) and the canine atopic dermatitis extent and severity index (CADESI). The reduction of pruritus was statistically significant using a Wilcoxon matched-pairs signed-ranks test (P < 0.001). No adverse side effects were observed. NT seems to be an effective alternative to control signs related to canine atopic dermatitis.

Gene expression in PBMC from severe atopic dermatitis patients assessed by high-density oligonucleotide arrays

2002 ◽  
Vol 109 (1) ◽  
pp. S111-S111
Author(s):  
Masayuki Heishi ◽  
Shinji Kagaya ◽  
T Katsunuma ◽  
Akira Akasawa ◽  
Akiko Nakada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atopic Dermatitis ◽  
High Density ◽  
Severe Atopic Dermatitis ◽  
Oligonucleotide Arrays

scholarly journals Possible Implication of Local Immune Response in Darier's Disease: An Immunohistochemical Characterization of Lesional Inflammatory Infiltrate

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Clelia Miracco ◽  
Francesco Pietronudo ◽  
Vasileios Mourmouras ◽  
Michele Pellegrino ◽  
Monica Onorati ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Infiltrate ◽  
Normal Skin ◽  
Pemphigus Vulgaris ◽  
Skin Lesions ◽  
Cell Mediated Immunity ◽  
Local Immune Response ◽  
Darier’S Disease ◽  
Darier's Disease

Cell-mediated immunity is considered to be normal in Darier's Disease (DD), an inherited skin disorder complicated by skin infections. To date, there are no investigations on the local inflammatory infiltrate in DD skin lesions. In this immunohistochemical study we characterized and quantified it, making comparisons with two other inflammatory skin disorders, that is, pemphigus vulgaris (PV) and lichen ruber planus (LRP), and with the normal skin (NSk). We found a significant () decrease of CD1a+ Langerhans cells (LCs) in DD, compared to PV, LRP, and NSk, and of CD123+ plasmacytoid dendritic cells (pDCs), compared to PV and LRP. We hypothesize that the genetic damage of keratinocytes might result in a loss of some subsets of dendritic cells and, consequently, in an impaired local immune response, which might worsen the infections that inevitably occur in this disease.

scholarly journals EMOLLIENT MILK XEMOSE IN THERAPY OF ATOPIC DERMATITIS IN CHILDREN

2014 ◽  
Vol 11 (4) ◽  
pp. 59-63
Author(s):  
E T KINDEEVA ◽  
N G KOROTKII ◽  
A N PAMPURA
Keyword(s):  
Atopic Dermatitis ◽  
Clinical Efficacy ◽  
Combined Therapy ◽  
Allergic Inflammation ◽  
Skin Barrier ◽  
Skin Surface ◽  
Skin Lesions ◽  
Transepidermal Water Loss ◽  
Skin Barrier Function ◽  
Epidermal Barrier

Background. Structural and functional damages of the epidermal barrier in patients with atopic dermatitis promote the entry of allergens and development of Th2-type allergic inflammation. Moisturizers containing lipids increase the physiological antiinflammatory effects of topical corticosteroids (TGKS), improve the epidermal barrier and reduce the duration of TGKS using preventing further infringement barrier. To evaluate the clinical efficacy of emollient milk Xemose in children with atopic dermatitis. Materials and methods. We examined 27 children with atopic dermatitis. Children were divided into 2 groups: patients in group 1 (n=14) used emollient milk Xemose twice a day on the skin lesions and limbs in the complex therapy, patients in the 2nd group (n=13) received combined therapy incorporating traditional dampening agents on the basis of lanolin (Unna cream) 3 times daily. All patients underwent measurement of transepidermal water loss (TEWl) (Tewameter TM 300, Multi Probe Adapter MPA 5/9, Courage + Khazaka) and the pH of the skin (Skin-pH-Meter, Multi Probe Adapter MPA 5/9, Courage + Khazaka) before and after 2 weeks of therapy. Results. Patients in groupthat used Xemose milk and children in group with Unna cream after 2 weeks showed a statistically significant decrease of TEWl (p=0,041 and p=0,04, respectively). TEWl was significantly lower in children treated for 2 weeks with milk Xemose (p=0,027) than in children treated with Unna cream. in both groups pH skin surface have not changed (р=0,22 and р=0,22 respectively). Conclusion. Clinical efficacy of milk Xemose as compound improving skin barrier function in children with atopic dermatitis was shown.

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