Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations

Abstract

Nuclear transcription factor B (NF-B) regulates innate and adaptive immunity functions and mediates inflammatory responses by activating proinflammatory cytokine gene transcription. TNF inhibitors block the NF-B signaling pathway, thus reducing inflammatory activity. The aim of the study was to evaluate the informativity of NF-kB transcription factor determination in the lymphocyte populations in children with inflammatory bowel disease (IBD) and psoriasis to assess the efficacy of anti-TNF therapy. We have examined 124 children with IBD and 55 children with psoriasis vulgaris administered maintenance anti-TNF therapy, and 30 healthy children. Stratification into the study groups was carried out according to PCDIA, PUCAI, PASI indices ( 10, remission). The number of cells with NF-B translocation was determined by flow cytometry with vusualization (Amnis ImageStreamX Mk II). Statistical evaluation was performed using Statistica 10.0 and SPSS 16.0. The highest number of cells with NF-B translocation was detected in B-lymphocytes and NK cells, thus being significantly higher than in T helper cells and cytotoxic T lymphocytes (p = 0.000). The percentage of cells with translocation of NF-B in populations of NK cells, T helper, cytotoxic T lymphocytes, Th17 lymphocytes, cytotoxic Th17 lymphocytes (Tc17) and Treg was increased in the patients at the acute disease stage against the comparison group. In the remission state, NF-B activity in lymphocyte populations was lower than in acute stage. In remission of psoriasis, NF-B activity in B lymphocytes, NK cells, and cytotoxic T lymphocytes was significantly lower than in comparison group. In IBD remission state, the NF-B activity was elevated only in T-helper cells. The level of NF-B translocation in the NK-cell population differed in children with IBD and psoriasis, both in acute phase (IBD, 46.2% (34-58); psoriasis, 36.5% (29-48), p = 0.041), and remission of disease (IBD, 25.4% (22-35); psoriasis, 19.1% (17-22), p = 0.000). ROC analysis of the data from exacerbation/remission states assessed as the NK cell numbers with NF-B translocation showed a good quality of the stratification model (AUC 0.8): The cut-off value in IBD was 41% (Se = 65.4; Sp = 89.1), and in psoriasis it was 23% (Se = 85.2; Sp = 94.7). The informativity of NF-B translocation level in lymphocyte populations in children with IBD and psoriasis was shown to correlate with efficacy of anti-TNF therapy. Exacerbation the disease with decreased therapeutic response is characterized by NF-B activation in lymphocyte populations in the children with IBD and psoriasis.

Nuclear transcription factor kB (NF-kB) activity in lymphocyte populations in children with Wilson-Konovalov disease

“…It is interesting to note that in children with WD, the translocation level indicators are comparable with those of the comparison group (medians do Medical Immunology (Russia)/Meditsinskaya Immunologiya Медицинская Иммунология not differ significantly), in contrast to children with autoimmune diseases (IBD, psoriasis), who have an increased level of NF-κB activity [4,10,11].…”

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

“…One of the factors of loss of response to GEBD therapy is the production of antibodies to biological drugs, and monitoring their level is recognized as a necessary criterion for controlling the ongoing treatment [5]. In recent years, there have been more and more cases of development of resistance to the ongoing therapy of GEBD in children, requiring replacement or withdrawal of the drug [5,12]. In this connection, the search for informative immunological criteria of effectiveness of biologics for psoriasis, as well as the identification of factors that lead to a decrease or absence of the effect of GEBD in patients with psoriasis, remains relevant.…”