Indicators of cellular immunity and myeloid-derived suppressor cells of myeloid origin in children with psoriasis

Купцова, Д. Г.; Радыгина, Т. В.; Мурашкин, Н. Н.; Петричук, С. В.

doi:10.14427/jipai.2020.3.55

Cited by 4 publications

(8 citation statements)

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“…The The content of MDSCs subpopulations was determined by stepwise gating according to a previously described algorithm [6], using multicolor flow cytometry: including the isolation of the "lymphoid-monocytic" region, the isolation of a population of cells that do not carry linear lymphocytic markers CD3, CD19, CD56 with PE fluorochrome and are negative for HLA-DR -FITC, the isolation of a double positive population for CD11b markers -APC-Cy7 and CD33 -Cy7, division of the subpopulation of MDSCs by expression of CD14 -PerCP and CD15 -APC (Beckman Coulter, Sony Biotechnology, USA). The MDSCs were phenotyped as monocytic (M-MDSCs) with the phenotype CD11b + CD14 + CD33 + HLA-DR -/low , granulocytic subpopulation (G-MDSCs) as CD11b + CD15 + CD33 + HLA-DR -/low and population cells negative CD14 and CD15 (М -G --MDSCs) with the phenotype CD11b + CD33 + HLA-DR -/low CD14 -CD15 -.…”

Section: Methodsmentioning

confidence: 99%

“…MDSCs modulate the immune response in a variety of diseases, including numerous types of cancer, inflammatory bowel disease, trauma, burns, infections, and transplants [2,3,11,13]. Previously, we showed that children with psoriasis have increased levels of MDSCs relative to healthy children [6]. Also, adult patients with psoriasis have been shown to have increased MDSCs in peripheral blood compared to healthy controls, which is associated with the severity and duration of the disease [2,3,8,15].…”

Section: Introductionmentioning

confidence: 98%

“…Psoriasis is a chronic inflammatory skin disease with hereditary predisposition and is characterized by increased proliferation of epidermal cells, impaired keratinization, and an inflammatory response in the dermis due to activation of T lymphocytes and synthesis of proinflammatory cytokines [1,6]. The pathophysiology of psoriasis is related not only to the activation of proinflammatory reactions, but also to a decrease in the anti-inflammatory functions of immunosuppressor cells.…”

Section: Introductionmentioning

confidence: 99%

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Role of myeloid-derived suppressor cells in prediction of the effectiveness of biologics in children with psoriasis

Kuptsova,

Radygina,

Freidlin

et al. 2023

Russian Journal of Immunology

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Psoriasis is a chronic inflammatory skin disease characterized by increased proliferation of epidermal cells, impaired keratinization, and an inflammatory reaction in the dermis due to activation of T-lymphocytes and synthesis of proinflammatory cytokines. Pathophysiology of psoriasis is associated not only with activation of proinflammatory reactions, but also with decreased anti-inflammatory functions of immunosuppressive cells. It is known that Treg, Breg and MDSCs do not perform their classical homeostatic functions in psoriasis. In recent years, there have been more and more cases of developing resistance to ongoing therapy with genetically engineered biological drugs (GEBD) in childhood, requiring replacement or discontinuation of the drug. The aim of our work was to estimate the content of MDSCs subpopulations and their functional activity in the peripheral blood of children with psoriasis at different effectiveness of biotherapeutic drugs. We examined 110 children with psoriasis vulgaris before the appointment of biologics, at 16 and 52 weeks of therapy with adalimumab, etanercept and ustikinumab, aged 6 to 18 years. Сomparison group consisted of 34 healthy children. The effectiveness of therapy was assessed by the achievement of PASI 75 by one year of therapy. Contents of myeloid-derived suppressor cells (MDSCs) and their subpopulations, and the activity of arginase-1 were assessed by multicolor flow cytometry. An increased content of MDSCs was found in children with psoriasis against the comparison group (p = 0.000). Analysis of the effectiveness of biologics in children with psoriasis, according to PASI, showed a significant reduction in disease severity in the group of patients with good effect, both at week 16 of therapy (p = 0.000) and by one year (p = 0.017). In the group of patients with good effect of biological therapy, percentage of total MDSCs population was higher, both before start of treatment and by 52nd week of therapy (p 0.01). Children with psoriasis showed increased immunosuppressive function of MDSCs by arginase-1 activity versus the comparison group (p = 0.000). The arginase-1 activity in patients with psoriasis at the stage of disease regression (PASI 10) was significantly increased relative to children in progressive stage of psoriasis (PASI10; p = 0.001). Thus, the content of MDSCs and their suppressive activity in children with psoriasis is an informative efficiency predictor of the biological drugs. Fading of biotherapy effect after the induction course is accompanied by decreased number of MDSCs and their functional activity.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of myeloid-derived suppressor cells in prediction of the effectiveness of biologics in children with psoriasis

Kuptsova,

Radygina,

Freidlin

et al. 2023

Russian Journal of Immunology

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“…It has been shown that in psoriasis, Th17 enhances the immune response of Th1 cells, mainly due to the production of IL-17A, which is responsible for the recruitment of neutrophils, activation of innate immunity cells, enhancement of B-cell functions and the release of pro-inflammatory cytokines [7,9]. A high percentage of Th17 cells have been found in the circulating and affected skin of psoriasis patients and a direct correlation has been established between the number of Th17 cells and the PASI (Psoriasis Area and Severity Index) [8,9,13].…”

Section: Introductionmentioning

confidence: 99%

“…The pathophysiology of psoriasis is not only related to the activation of pro-inflammatory reactions, but also to a decrease in the anti-inflammatory functions of immunosuppressive cells [10,11]. It has been shown that regulatory T cells (Treg), regulatory B cells and myeloid-derived suppressor cells (MDSCs) do not perform their classical homeostatic functions in psoriasis [8,10,11]. It is known that Tregs are able to suppress the activation and proliferation of effector cells through the production of TGF-β and IL-10 [5,12].…”

Section: Introductionmentioning

confidence: 99%

Content of CD4<sup>+</sup>T cell subpopulations in predicting the efficacy of biological therapy for psoriasis in children

et al. 2023

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Psoriasis is a chronic inflammatory skin disease characterized by increased proliferation of epidermal cells, impaired keratinization and an inflammatory reaction in dermis caused by activation of T lymphocytes and synthesis of pro-inflammatory cytokines. The pathophysiology of psoriasis is also associated with a decrease in anti-inflammatory functions of immunosuppressive cells. Recently, there are more cases of development of resistance to ongoing therapy with biologics in children, requiring cancellation of drug or its replacement. The aim of the study was to evaluate the content of T helper subpopulations in prognosis of effectiveness of biologics in children with psoriasis. Immunophenotyping of T helper populations was performed in 110 children with psoriasis vulgaris before appointment of biologics, at 16 and 52 weeks. Age of children ranged from 6 to 18 years. Severity of psoriasis and effectiveness of therapy were assessed by index PASI, which varied 0-68. Content of Tregs, Thact and Th17 was determined by flow cytometry. In group with a sufficient effect of biologics, a decrease in PASI was obtained, both at week 16 of therapy (p = 0.000) and by year of treatment, p = 0.017. In children with psoriasis, regardless of duration and effectiveness of biologics, percentage of Thact was increased relative to normal values. In group 1 before prescription of biologics was increased percentage of Thact (p = 0.005) and Th17 (p = 0.001). Analysis of dynamics of content of small populations of T helper during 1 year of use of biologics in children with different efficacy of therapy showed that significant changes were found in content of Th17 and Treg, as well as their Th17/Treg. ROC analysis showed that when Th17 deviation was above 53%, Thact above 181% and Th17/Treg above 2.6 before biologics were prescribed, insufficient efficacy of therapy could be expected in 75% of cases by year. By the end of induction course, with a Th17 deviation above 102% and a Th17/Treg above 2.6, probability of ineffective treatment was already 82%. The study shows the informative value of assessment of Thact before appointment of biologics, dynamics of Th17 by the end of induction course and Treg after 16 weeks of therapy in prognosis of effectiveness of biologics in children with psoriasis.

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Activity of nuclear factor κB in lymphocyte populations of children with psoriasis

Купцова

Petrichuk

Murashkin

et al. 2022

BRSMU

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Alterations in intracellular signaling pathways affecting immune cell activation, proliferation and differentiation of keratinocytes in psoriasis could explain the complex pathogenesis of the disease. NF-κB is one of the intracellular signaling pathways, which is involved in regulation of numerous pro-inflammatory genes, and affects the synthesis of pro-inflammatory cytokines directly involved in the development of psoriasis. The study was aimed to assess the number of cells with NF-κB translocation in lymphocyte populations of children with psoriasis depending in the disease severity and therapy. A total of 130 children with psoriasis vulgaris were examined. The comparison group included 30 healthy children. The study was conducted using the imaging flow cytometry Amnis ImageStreamX system. It was found that there were significant differences in the number of cells with NF-κB translocation in the lymphocyte populations of both children with psoriasis and comparison group. Children with psoriasis had a higher number of cells with NF-κB translocation in the populations of T helper cells, Tact, Treg, and Th17 compared to healthy children (p < 0.05). The number of cells with NF-κB translocation in children with psoriasis correlated with the disease severity PASI (Rmul = 0.32) and BSA (Rmul = 0.31) scores, as well as with the disease duration (p < 0.05). NF-κB determination could be considered an additional criterion for the disease severity assessment in children with psoriasis. The differences in the degree of reduction of the number of cells with NF-κB translocation 24 h after administration of biologics (adalimumab, etanercept, ustekinumab) have been shown. Studying NF-κB in cell populations offers the prospect of understanding pathogenetic mechanisms of inflammation and developing new therapeutic methods for psoriasis.

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Indicators of cellular immunity and myeloid-derived suppressor cells of myeloid origin in children with psoriasis

Cited by 4 publications

References 0 publications

Role of myeloid-derived suppressor cells in prediction of the effectiveness of biologics in children with psoriasis

Role of myeloid-derived suppressor cells in prediction of the effectiveness of biologics in children with psoriasis

Content of CD4<sup>+</sup>T cell subpopulations in predicting the efficacy of biological therapy for psoriasis in children

Activity of nuclear factor κB in lymphocyte populations of children with psoriasis

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