Dataset Information

Cytokine and Lymphocyte Profiles in Dogs with Atopic Dermatitis after Allergen-Specific Immunotherapy.

ABSTRACT: Canine atopic dermatitis (cAD) is a chronic and recurrent inflammatory and pruritic skin disease in dogs. Currently, allergen-specific immunotherapy (ASIT) is the only identified disease-modifying intervention for allergic diseases. It decreases the symptoms triggered by allergens and prevents recurrence of the disease in the long-term. The aim of our research was to determine how immunotherapy changes the proportion of lymphocyte subsets in dog peripheral blood and the levels of cytokines secreted by these cells during therapy. ASIT was applied for 6 months. Blood samples for further analyses were collected from patients in the third and sixth month of immunotherapy. Six out of seven dogs receiving ASIT showed a positive effect. A reduction in cytokine levels (IL-13, TNF-α) in peripheral blood of cAD patients and changes in the number of specific T cell subpopulations-reduction of Tc cells (CD8⁺) and increase of activated T cells (CD3⁺CD25⁺)-confirmed the beneficial effect of the applied ASIT. In addition, a significantly higher percentage of Treg cells (CD4⁺CD25⁺FOXP3⁺) was noted in cAD patients before treatment compared to healthy dogs. After 3 months of therapy, the percentage of Tregs significantly decreased, and after 6 months, it increased significantly again.

SUBMITTER: Majewska A

PROVIDER: S-EPMC9323343 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Cytokine and Lymphocyte Profiles in Dogs with Atopic Dermatitis after Allergen-Specific Immunotherapy.

Majewska Alicja A Dembele Kourou K Dziendzikowska Katarzyna K Prostek Adam A Gajewska Małgorzata M

Vaccines 20220628 7

Canine atopic dermatitis (cAD) is a chronic and recurrent inflammatory and pruritic skin disease in dogs. Currently, allergen-specific immunotherapy (ASIT) is the only identified disease-modifying intervention for allergic diseases. It decreases the symptoms triggered by allergens and prevents recurrence of the disease in the long-term. The aim of our research was to determine how immunotherapy changes the proportion of lymphocyte subsets in dog peripheral blood and the levels of cytokines secre ...[more]

PMID: 35891200

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Project description:BackgroundCanine atopic dermatitis (cAD) is a common chronic and pruritic skin disease in dogs. The development of cAD involves complex interactions between environmental antigens, genetic predisposition and a number of disparate cell types. The aim of the present study was to perform comprehensive analyses of peripheral blood of AD dogs in relation to healthy subjects in order to determine the changes which would be characteristic for cAD.ResultsThe number of cells in specific subpopulations of lymphocytes was analyzed by flow cytometry, concentration of chosen pro- and anti-inflammatory cytokines (IL-4, IL-10, IL-13, TNF-α, TGF-β1) was determined by ELISA; and microarray analysis was performed on RNA samples isolated from peripheral blood nuclear cells of AD and healthy dogs. The number of Th cells (CD3(+)CD4(+)) in AD and healthy dogs was similar, whereas the percentage of Tc (CD3(+)CD8(+)) and Treg (CD4(+)CD25(+) Foxp3(+)) cells increased significantly in AD dogs. Increased concentrations of IL-13 and TNF-α, and decreased levels of IL-10 and TGF-β1 was observed in AD dogs. The level of IL-4 was similar in both groups of animals. Results of the microarray experiment revealed differentially expressed genes involved in transcriptional regulation (e.g., transcription factors: SMAD2, RORA) or signal transduction pathways (e.g., VEGF, SHB21, PROC) taking part in T lymphocytes lineages differentiation and cytokines synthesis.ConclusionsResults obtained indicate that CD8(+) T cells, beside CD4(+) T lymphocytes, contribute to the development of the allergic response. Increased IL-13 concentration in AD dogs suggests that this cytokine may play more important role than IL-4 in mediating changes induced by allergic inflammation. Furthermore, observed increase in Treg cells in parallel with high concentrations of TNF-α and low levels of IL-10 and TGF-β1 in the peripheral blood of AD dogs point at the functional insufficiency of Treg cells in patients with AD.

Project description:Abstract Background Atopic dermatitis (AD), a chronic inflammatory disorder, is often accompanied by allergic rhinoconjunctivitis (ARC) as a co‐morbidity. The use of a monoclonal anti‐IL‐4Rα antibody has been effective in controlling moderate to severe AD symptoms. Allergen‐specific immunotherapy (AIT) is widely used for the treatment of ARC and asthma. The effects of AIT on basophil reactivity/effector functions have already been examined and used as indicators of the treatment efficacy. However, it is unclear, how an anti‐IL‐4Rα antibody can influence allergen‐specific immune responses of basophils and T cells of AD patients with comorbid ARC. Objective To investigate the effect of a monoclonal anti‐IL‐4Rα antibody on the in vitro allergic responses of basophils and T cells deriving from AD patients with comorbid ARC. Methods Blood samples of 32 AD patients were obtained before, after 4 and 16 weeks of an anti‐IL‐4Rα antibody therapy (300 mg subcutaneously/2 weeks; n = 21) or AIT (daily sublingual application; n = 11). Patients treated with an anti‐IL‐4Rα antibody were grouped according to their serum specific immunoglobulin E levels and ARC symptoms, while patients receiving an AIT were additionally grouped according to the allergen specificity of their AIT. Basophil activation test and T cell proliferation assays were undertaken after an in vitro allergen stimulation. Results A significant reduction of the immunoglobulin E levels and the allergen‐specific T cell proliferation was observed in AD patients treated with an anti‐IL‐4Rα ‐antibody, while the allergen‐specific basophil activation/sensitivity were found to be significantly increased. In patients receiving an AIT, the in vitro allergen‐specific basophil activation and the T cell proliferation were found to be significantly decreased in response to seasonal allergens. Conclusions An IL‐4Rα blockade induced by a monoclonal anti‐IL‐4Rα antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late‐phase T cell reaction to allergens did not differ between the herein assessed treatments. The purpose of our study was to investigate the effect of a monoclonal anti‐IL‐4Rα antibody on the in vitro allergic response of basophils and T cells deriving from AD patients with comorbid ARC. We conclude, that an IL‐4Rα blockade induced by a monoclonal anti‐IL‐4Rα‐antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late‐phase T cell reaction to allergens did not differ between the herein assessed treatments. Key messages Total‐ and specific IgE levels decreased in AD patients treated with an anti‐IL‐4Rα antibody during the observational period of 16 weeks, but not in patients treated with AIT. Allergen‐specific activation and sensitivity increased significantly after allergen stimulation of basophils of AD patients treated with an anti‐IL‐4Rα antibody for 16 weeks, but decreased under birch‐specific AIT. T cell antigen‐specific response to seasonal allergens was reduced in AD patients treated with an anti‐IL‐4Rα antibody or AIT.

Project description:BackgroundAtopic dermatitis (AD) is an inflammatory chronic condition that affects the skin of children and adults and has an important impact on the quality of life. Treatments for AD are based on environmental controls, topical and systemic therapies, and allergen-specific immunotherapy (AIT). However, it remains unclear the effectiveness and adverse events of AIT and all conventional topical treatments compared with placebo and each other for AD.MethodsWe will search five electronic databases [Central Cochrane register of controlled trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and LILACS] from inception until November 2019 with no language restriction, and we will include experimental studies [randomized controlled trials (RCTs), and quasi-RCTs]. The primary outcome is global and specific skin symptoms assessment. Secondary outcomes are hospital length of stay, quality of life, and adverse events. Reviewers independently will extract data from the studies that meet our inclusion criteria and will assess the risk of bias of individual primary studies. We will conduct random effects pairwise meta-analyses for the observed pairwise comparisons with at least two trials. Then, we will perform random-effects Bayesian network meta-analysis (NMA) to obtain treatment effects for all possible comparisons and to provide a hierarchy of all interventions for each outcome. Possible incoherence between direct and indirect sources of evidence will be investigated locally (if possible) and globally. To investigate sources of statistical heterogeneity, we will perform a series of meta-regression analyses based on pre-specified important effect modifiers. Two authors will appraise the certainty of the evidence for each outcome applying the GRADE's framework for NMA.DiscussionThe findings of this systematic review will shed the light on the effectiveness and adverse events of all possible comparisons for treating AD and on the quality of the collated evidence for recommendations. It will also provide critical information to health care professionals to comprehend and manage this disease at different age stages, treatment type, duration, and severity of atopic dermatitis.Systematic review registrationPROSPERO Protocol ID CRD42019147106.

Dataset Information

Cytokine and Lymphocyte Profiles in Dogs with Atopic Dermatitis after Allergen-Specific Immunotherapy.

Publications

Cytokine and Lymphocyte Profiles in Dogs with Atopic Dermatitis after Allergen-Specific Immunotherapy.

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