The aim of this study was to assess the relationship between the expression of the CD23 molecule on B-cells and the levels of specific IgE against allergens and molecular components of storage mites (Gly d 2, Lep d 2), dog (Can f 1, Can f 2), cat (Fel d 1), shrimp (Pen m 2), molds (Asp f 6, Mala s 11, Alt a 6, Alt a 1, Mala s 6, Cla h), and German cockroach (Bla g 9) in atopic dermatitis (AD) patients (with and without dupilumab therapy). Here, 46 patients with AD were included (26 without dupilumab treatment, 20 with dupilumab treatment). Serum levels of specific IgE were measured using the component-resolved diagnostic microarray ALEX2 Allergy Xplorer, and the expression of the CD23 molecule on B-cells was evaluated using flow cytometry. For statistical analysis, a Spearman's rank correlation was used. The data indicated there was a higher correlation between CD23 expression on B-cells and specific IgE against molecular components of storage mites Bla g 9 (up to 27%), cat Fel d 1 (22.7%), and allergen extract Cla h (Cladosporium herbarum) up to 38.9% in AD patients treated with dupilumab. These results regarding the higher association suggested a significant role in the non-inflammatory clearance and uptake of these specific IgE antibodies.

What is already known about this topic? It is not yet known whether the expression of molecule CD23 on B-cells is related to the level of allergen-specific IgE antibodies in AD patients. It is also not yet known what role dupilumab may have on this receptor.What does this article add to our knowledge? The study investigated the relationship between CD23 expression on B-cells and specific IgE levels of storage mites (Gly d 2, Lep d 2), dog (Can f 1, Can f 2), cat (Fel d 1), shrimps (Pen m 2), molds (Asp f 6, Mala s 11, Alt a 6, Alt a 1, Mala s 6, Cla h), and German cockroach (Bla g 9) in patients with atopic dermatitis (AD), both with and without dupilumab treatment.How does this study impact current management guidelines? The study provides insights into how dupilumab influences IgE interactions and allergic inflammation, potentially guiding more targeted treatments for AD patients. The findings suggest that dupilumab therapy may be more effective in AD patients sensitized to allergen extract Cla h (Cladosporium herbarum) due to its role in reducing inflammatory responses.

• Klíčová slova
• Atopic dermatitis, CD23 molecule on B lymphocytes, specific IgE against molecular components,
• MeSH
• alergeny imunologie   MeSH
• atopická dermatitida * imunologie   farmakoterapie   MeSH
• B-lymfocyty * imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• houby imunologie   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoglobulin E * krev   imunologie   MeSH
• kočky MeSH
• kvasinky imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• psi MeSH
• receptory IgE * metabolismus   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kočky MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alergeny MeSH
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• imunoglobulin E * MeSH
• receptory IgE * MeSH

The aim of the study here was to evaluate the association between expression of CD23 molecule on B-lymphocytes and the level of specific IgE to molecular components of birch, Bermuda grass, hazel pollen, timothy, and rye grass in atopic dermatitis (AD) patients (with and without dupilumab therapy). A total of 46 patients suffering from AD were included: 26 without dupilumab treatment and 20 with dupilumab treatment. Serum levels of specific IgE were measured by the components resolved diagnostic assay ALEX2 Allergy Xplorer, the expression of CD23 molecule on B-lymphocytes was evaluated with flow cytometry. For the statistical analysis, the Spearman's rank correlation coefficient was used. In patients treated with dupilumab, the higher association was observed between the expression of CD23 on B-lymphocytes and specific IgE to molecular components Bet v 1, Cor a 1.0103, Cor a 1.0401, and Phl p 1. This study demonstrated that the relationship between CD23 expression on B-lymphocytes and specific IgE to pollen molecular components varies depending on whether the patient was treated with dupilumab and the type of molecular component involved.

What is already known about this topic?It is not yet known whether the expression of molecule CD23 on B lymphocytes is related to the level of allergen-specific IgE antibodies in AD patients. It is also not yet known what role dupilumab may have on this receptor.What does this article add to our knowledge?The study investigated the relationship between CD23 expression on B lymphocytes and specific IgE levels to various pollen molecular components in patients with atopic dermatitis (AD), both with and without dupilumab treatment.How does this study impact current management guidelines?The study provides insights into how dupilumab influences IgE interactions and allergic inflammation, potentially guiding more targeted treatments for AD patients.The findings suggest that dupilumab therapy may be more effective in AD patients sensitized to specific molecular components like Bet v 1, Cor a 1.0103, Cor a 1.0401, and Phl p 1, due to its role in reducing inflammatory responses.

• Klíčová slova
• Atopic dermatitis, B lymphocytes, CD23 molecule, dupilumab, molecular components, specific IgE,
• MeSH
• alergeny imunologie   MeSH
• atopická dermatitida * imunologie   farmakoterapie   MeSH
• B-lymfocyty * imunologie   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• imunoglobulin E * krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pyl * imunologie   MeSH
• receptory IgE * metabolismus   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alergeny MeSH
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• imunoglobulin E * MeSH
• receptory IgE * MeSH

BACKGROUND: There are a lot of studies that describe the change in quantity of T cells in patients with atopic dermatitis (AD) compared with healthy subjects. Other components of lymphocytes such as B cells are not examined as well as T cells. OBJECTIVE: We focus on immunophenotyping of B cells with their subsets (memory, naïve, switched, non-switched) and the expression of CD23 and CD200 markers in patients with AD with and without dupilumab therapy. We also evaluate the count of leukocytes and their subsets, T lymphocytes (CD4+, CD8+), natural killer (NK) cells, and T regulatory cells. METHODS: A total of 45 patients suffering from AD were examined: 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. We compared the absolute and relative count of leukocytes and their subsets, T lymphocytes (CD4+ , CD8+), NK cells, T regulatory cells, absolute and relative count of B lymphocytes (memory, naïve, non-switched, switched, transient), and expression of CD23 and CD200 activation markers on B cells and on their subsets in patients with AD and control group. For statistical analysis we used nonparametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification of significance level. RESULTS: In patients with AD with and without dupilumab therapy we confirmed the significantly higher count of neutrophils, monocytes, and eosinophils; there was no difference in absolute count of B cells, NK cells and transitional B cells compared with control subjects. We confirmed higher expression of activation marker CD23 on total, memory, naïve, non-switched, and switched B lymphocytes and higher expression of CD200 on total B lymphocytes in both groups of patients with AD compared with controls. In patients without dupilumab therapy we confirmed significantly higher count of relative monocytes, relative eosinophils, and higher expression of CD200 on memory, naïve, and non-switched B lymphocytes compared with controls. In patients with dupilumab therapy we confirmed significantly higher expression of CD200 on switched B lymphocytes, higher count of relative CD4+ T lymphocytes, and lower count of absolute CD8+ T lymphocytes compared with controls. CONCLUSION: This pilot study shows higher expression of CD23 on B lymphocytes and on their subsets in patients with AD with and without dupilumab therapy. The higher expression of CD200 on switched B lymphocytes is confirmed only in patients with AD with dupilumab therapy.

• Klíčová slova
• Atopic dermatitis expression of activation marker CD23, CD200 on B cells dupilumab,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Eosinophils, basophils, and the molecule CD23 on B cells are involved in the pathophysiology of atopic dermatitis (AD). The molecule CD23 is involved in the regulation of IgE synthesis and is expressed by activated B cells. The molecule CD16 is used to assess the activation of eosinophils and CD203 of basophils. The association between the count of eosinophils, basophils, CD16+ eosinophils, CD203+ basophils and the expression of the activation marker CD23 on B cells in patients with AD (with and without dupilumab therapy) is not described. OBJECTIVE: The aim of this pilot study is to evaluate the association between the blood count of eosinophils, basophils, relative CD16+ eosinophils, relative CD203+ basophils, and the expression of molecule CD23 on B cells and on their subsets (total, memory, naive, switched, non-switched) in patients suffering from AD (with and without dupilumab therapy) and in control group. METHODS: A total of 45 patients suffering from AD were examined; 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. For statistical analysis we used non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification and the Spearman's rank correlation coefficient; for coefficients higher than 0.41, we report R2 (percent of variation explained). RESULTS: The absolute count of eosinophils was significantly higher in patients with AD (with and without dupilumab) in comparison to healthy subjects. The difference in the relative count of CD16+ eosinophils in patients with AD (with and without dupilumab therapy) compared with control is not statistically significant. In patients with dupilumab therapy the significantly lower count of relative CD203+ basophils was confirmed compared with control. The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with dupilumab therapy; in contrast, this association was low in patients with AD without dupilumab therapy and in healthy subjects. CONCLUSION: The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with AD under dupilumab therapy. It suggests that IL-4 production by eosinophils may play a role in B lymphocyte activation. The significantly lower count of CD203+ basophils has been demonstrated in patients with dupilumab therapy. This reduction of CD203+ basophil count may contribute to the therapeutic effects of dupilumab by reducing the inflammatory response and allergic reactions in patients with AD.

• Klíčová slova
• Activation markers CD16, Atopic dermatitis patients, Basophils, CD203, Dupilumab therapy, Eosinophils, Expression of CD23 on B cells,
• Publikační typ
• časopisecké články MeSH

• MeSH
• atopická dermatitida * MeSH
• B-lymfocyty MeSH
• humanizované monoklonální protilátky MeSH
• lidé MeSH
• roční období MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH

BACKGROUND: The CD23 molecule has an effect on the regulation of IgE synthesis, either by stimulation or inhibition. It is not yet known whether the expression of CD23 on B lymphocytes is related to the level of allergen-specific IgE antibodies in patients with atopic dermatitis. AIM: The aim of this pilot study was to evaluate the association between the expression of CD23 molecule on B cells and on their subsets (memory, naive, switched, non-switched, and total B lymphocytes) and the level of specific IgE to molecular components of mites in atopic dermatitis patients (with and without dupilumab therapy). METHODS: Forty-five patients suffering from atopic dermatitis were included: 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years) and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). The serum level of the specific IgE was measured using the components resolved diagnostic microarray-based specific IgE detection assay ALEX2 Allergy Xplorer. In all included patients, the expression of CD23 molecule on B lymphocytes was evaluated with flow cytometry using monoclonal antibodies. For the statistical analysis of the association between expression of CD23 molecule on B lymphocytes and the level of specific IgE to molecular components of mites, we used non-parametric Kruskal-Wallis one-factor analysis of variance with post-hoc by Dunn's test with Bonferroni modification and the Spearman's rank correlation coefficient; for coefficients higher than 0.41, we report R2 (%, percent of Variation Explained). RESULTS: The association between the expression of CD23 molecule on B cells and the level of specific IgE to molecular components of mites was confirmed only in patients with dupilumab therapy. In these patients, the highest association was confirmed between the level of specific IgE to Der p 20 and expression of CD23 on switched B lymphocytes (in 48.9%). In patients without dupilumab, the association between the level of specific IgE to molecular components of mites and the expression of CD23 on B cells and on their subsets is low. CONCLUSION: Further research is needed to fully understand the underlying mechanism of this phenomenon and its implications for the treatment of atopic dermatitis.

• Publikační typ
• dopisy MeSH

BACKGROUND: The data on the clinical utility of the quantitative assessment of immunophenotypes in distinguishing mature CD5-positive B-cell neoplasms is limited. The study aim was to assess the diagnostic value of the quantitative assessment of a panel of 18 markers and to identify the most informative ones. METHODS: The immunophenotype of the neoplastic population was determined in diagnostic specimens from 188 patients. BD FACSCanto II flow cytometer and FACSDiva software were used to analyze the positivity/negativity and mean fluorescence intensity (MFI) of the surface expression of 18 markers. Advanced data mining methods were used to define the key differential diagnostic features of CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma), MCL (mantle cell lymphoma), and CD5+ MZL (marginal zone lymphoma). RESULTS: The most informative markers for the distinction of CLL/SLL, MCL, CD5+ MZL, including atypical cases, were the MFI values of CD79b, CD20, CD23, CD43, CD38, CD11c, FMC7, CD200, kappa light chain, and their combinations. CD23 and CD200 were the most discriminant between CLL/SLL and MCL and CD23 plus CD79b between CLL/SLL and CD5+ MZL. The quantitative analysis of the most informative markers failed to accurately distinguish MCL and CD5+ MZL. The study highlights the data mining methods for the analysis and selection of the most informative immunophenotypic markers and for the design of a predictive model (diagnostic classifier), minimizing the subjectivity of expert-based assessment. CONCLUSIONS: Our data confirmed that the quantification of the expression of informative markers increases the diagnostic value of immunophenotyping in mature CD5+ B-cell neoplasms. © 2017 International Clinical Cytometry Society.

• Klíčová slova
• B-cells, flow cytometry, immunophenotyping, leukemia, lymphoma,
• MeSH
• antigeny CD5 analýza   MeSH
• B-buněčný lymfom diagnóza   imunologie   MeSH
• dospělí MeSH
• imunofenotypizace metody   MeSH
• leukemie B-buněčná diagnóza   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   imunologie   MeSH
• průtoková cytometrie metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD5 MeSH
• nádorové biomarkery MeSH

OBJECTIVE: The aim of the study is to analyze the absolute count of leukocytes, neutrophils, monocytes, eosinophils, T cells, natural killer cells, B cells and to evaluate the expression of functionally important CD23 and CD200 molecules on B cells in patients suffering from atopic dermatitis (AD), (with and without dupilumab therapy). MATERIALS AND METHODS: We examined 45 patients suffering from AD - 32 patients without dupilumab treatment (10 men, 22 women, average age 35.0 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years) and 30 healthy control (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry (Navios Flow Cytometer - Beckman Coulter). The blood count was examined with a Sysmex XN 3000, Sysmex SP10, microscope DI60 for digital morphology evaluating cell division and microscope Olympus BX40. We compared the absolute count of leukocytes and their subsets, T cells (CD4, CD8), natural killers cells, absolute and relative count of B lymphocytes and expression of surface molecules CD23 and CD200 on B cells in AD patients and in control group. Non-parametric Kruskal-Wallis one-factor analysis of variance with post-hoc (follow-up multiple comparison) and Dunn's test with Bonferroni modification of significance level were used for statistical analysis. RESULTS: We confirmed the significantly higher number of neutrophils, monocytes and eosinophils and higher expression of CD23 and CD200 on B cells in peripheral blood of AD patients (either with or without dupilumab) therapy. We demonstrated the lower number of CD8+ T cells. CONCLUSION: We demonstrated the difference in the count of white blood cells populations in patients suffering from AD compared with healthy control. There were a differences in the expression of immunoregulatory molecules CD23 and CD200 on B cells in AD patients (either with or without dupilumab therapy) in comparison to healthy controls.

• Klíčová slova
• B cells, CD200, CD23, NK cells, T cells, atopic dermatitis, immunophenotyping,
• MeSH
• atopická dermatitida * farmakoterapie   MeSH
• B-lymfocyty MeSH
• dospělí MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• lidé MeSH
• monocyty MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH

Mast cells and basophils (MCs/Bs) play a crucial role in type I allergy, as well as in innate and adaptive immune responses. These cells mediate their actions through soluble mediators, some of which are targeted therapeutically by, for example, H1- and H2-antihistamines or cysteinyl leukotriene receptor antagonists. Recently, considerable progress has been made in developing new drugs that target additional MC/B mediators or receptors, such as serine proteinases, histamine 4-receptor, 5-lipoxygenase-activating protein, 15-lipoxygenase-1, prostaglandin D2, and proinflammatory cytokines. Mediator production can be abrogated by the use of inhibitors directed against key intracellular enzymes, some of which have been used in clinical trials (eg, inhibitors of spleen tyrosine kinase, phosphatidylinositol 3-kinase, Bruton tyrosine kinase, and the protein tyrosine kinase KIT). Reduced MC/B function can also be achieved by enhancing Src homology 2 domain-containing inositol 5' phosphatase 1 activity or by blocking sphingosine-1-phosphate. Therapeutic interventions in mast cell-associated diseases potentially include drugs that either block ion channels and adhesion molecules or antagonize antiapoptotic effects on B-cell lymphoma 2 family members. MCs/Bs express high-affinity IgE receptors, and blocking their interactions with IgE has been a prime goal in antiallergic therapy. Surface-activating receptors, such as CD48 and thymic stromal lymphopoietin receptors, as well as inhibitory receptors, such as CD300a, FcγRIIb, and endocannabinoid receptors, hold promising therapeutic possibilities based on preclinical studies. The inhibition of activating receptors might help prevent allergic reactions from developing, although most of the candidate drugs are not sufficiently cell specific. In this review recent advances in the development of novel therapeutics toward different molecules of MCs/Bs are presented.

• Klíčová slova
• Mast cell, basophil, drug, mediator, receptor, signaling protein, survival protein, therapy,
• MeSH
• alergie imunologie   terapie   MeSH
• antialergika farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• bazofily imunologie   MeSH
• cílená molekulární terapie MeSH
• degranulace buněk účinky léků   MeSH
• imunoterapie metody   trendy   MeSH
• iontové kanály antagonisté a inhibitory   MeSH
• lidé MeSH
• mastocyty imunologie   MeSH
• molekuly buněčné adheze antagonisté a inhibitory   MeSH
• receptory IgE antagonisté a inhibitory   MeSH
• receptory kanabinoidní metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antialergika MeSH
• iontové kanály MeSH
• molekuly buněčné adheze MeSH
• receptory IgE MeSH
• receptory kanabinoidní MeSH

Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni's modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8+ T lymphocytes. Why carry out this study?Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5+, CD22+ and CD73+ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy.What was learned from the study?In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes.In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16+ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8+ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8+ T lymphocytes and their subpopulations.In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes.The changes in the count of CD5+, CD22+ and CD73+ B lymphocytes were not observed during pollen season in both groups of AD patients.

• Klíčová slova
• B lymphocytes, Dupilumab, T lymphocytes, atopic dermatitis,
• MeSH
• atopická dermatitida * farmakoterapie   imunologie   MeSH
• B-lymfocyty * imunologie   MeSH
• CD antigeny metabolismus   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigens, CD200 MeSH Prohlížeč
• CD antigeny MeSH
• dupilumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH