INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE

Петричук, С. В.; Miroshkina, L.; Семикина, Е. Л.; Топтыгина, А. П.; Потапов, А. С.; Цимбалова, Е. Г.; Радыгина, Т. В.

doi:10.15789/1563-0625-2018-5-721-730

Cited by 3 publications

(5 citation statements)

References 24 publications

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“…Альтернативно уменьшение или отсутствие противовоспалительных микробов может привести к недостаточному развитию субпопуляции Treg [6,9]. Характерные изменения в субпопуляционном составе лимфоцитов периферической крови при ВЗК предопределяют эффективность биологической терапии [2]. Этот дисбаланс приводит к изменению цитокинового профиля в крови пациентов, но особенно эти изменения выражены на местном уровне [3].…”

Section: Diagnostic Value Of Anti-gp2 Antibodies Determined In Serum unclassified

“…Целью исследования было изучение уровня анти-GP2-антител в крови и фекалиях детей с ВЗК по сравнению с группой ДБ. Исследованы сыворотки крови и копрофильтраты от 110 детей (64 мальчика и 46 девочек) в возрасте 12,3 (2,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)9) года; 36 пациентов с БК, 30 пациентов с ЯК, группу сравнения составили 44 пациента с ДБ. Антитела IgG и IgA против GP2 тестировали методом ИФА.…”

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“…Применены методы непараметрической статистики, результаты представлены в процентах и медианах -Me (Q 0,25 -Q 0,75 ). Уровни сывороточных IgA-антител против GP2 составили у пациентов с БК 9,97 (3,45) Ед/мл, для ЯК 6,08 (2,26) Ед/мл и для ДБ 2,94 (2,29-6,41) Ед/ мл. Уровни анти-GP2 IgG-антител в сыворотках крови составили 6,16 (3,4) Ед/мл для БК, 5,26 (2,97-7,52) Ед/мл для ЯК и для ДБ 5,23 (2,85) Ед/мл.…”

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“…Уровни сывороточных IgA-антител против GP2 составили у пациентов с БК 9,97 (3,45) Ед/мл, для ЯК 6,08 (2,26) Ед/мл и для ДБ 2,94 (2,29-6,41) Ед/ мл. Уровни анти-GP2 IgG-антител в сыворотках крови составили 6,16 (3,4) Ед/мл для БК, 5,26 (2,97-7,52) Ед/мл для ЯК и для ДБ 5,23 (2,85) Ед/мл. Пороговая концентрация cut-off для анти-GP2 антител класса IgG составила 13,8 Ед/мл, чувствительность -63,2%, специфичность -100%, а для IgA -5,63 Ед/мл при чувствительности 60,5% и специфичности -78,8%, что ниже рассчитанного cut-off взрослых -20 Ед/ мл.…”

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“…и др. Medical Immunology (Russia)/Meditsinskaya Immunologiya Медицинская Иммунология концентрация sIgA в копрофильтратах больных с ВЗК значимо превышала уровень группы с ДБ. Соотношение анти-GP2 IgA/sIgA было значительно ниже у пациентов с БК (0,326 (0,23-0,512)), и ЯК (0,327 (0,205-0,435)), чем у пациентов с ДБ (2,332 (1,575-3,523)) (р < 0,001); cut-off составил 0,784 с чувствительностью 97,7% и специфичностью 98,6%. Обсуждается, что анти-GP2 IgA антитела в фекалиях следует рассматривать как протективные, поддерживающие гомеостаз в кишечнике, а анти-GP2 IgG антитела являются патогенетически значимыми для развития ВЗК.…”

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Diagnostic value of anti-GP2 antibodies determined in serum and coprofiltrates in children with inflammatory bowel disease

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Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronically recurring inflammation of intestinal wall and are associated with a significant decrease in the quality of life. A spectrum of genetic variants associated with Crohn’s disease is described. Intestinal dysbiosis (DB) may be the triggering factor of the disease. Glycoprotein 2 (GP2), the main protein of pancreatic zymogen granules, is secreted into the intestines with digestive enzymes. Anti-GP2 antibodies were found in the serum of patients with CD. The aim of the present study was to investigate the levels of anti-GP2 antibodies in serum and feces of children with IBD compared with the DB group. Serums and coprofiltrates from 110 children (64 boys and 46 girls) at the age of 12.3 (2.6-17.9) years were studied; 36 patients with CD, 30 patients with UC. A comparison group consisted of 44 patients with DB. IgG and IgA antibodies against GP2 were tested with ELISA. Nonparametric statistics methods are applied, the results are presented as percentages and medians (Me (Q0.25-Q0.75)). The serum levels of anti-GP2 IgA antibodies were 9.97 (3.35-13.45) U/ml for the CD patients, 6.08 (2.71-14.26) U/ml for UC and 2. 94 (2.29-6.41) U/ml for DB. The levels of anti-GP2 IgG antibodies in serum were 6.16 (3.26-18.4) U/ml for CD, 5.26 (2.97-7.52) U/ml for UC, and for DB 5.23 (2.53-8.85) U/ml. The cut-off threshold concentration for anti-GP2 IgG antibodies was 13.8 U/ml, with sensitivity of 63.2%, specificity 100%, and for IgA 5.63 U/ml, with sensitivity of 60.5% and specificity of 78.8%, thus being lower than the calculated cut-off for adults (20 U/ml). The levels of anti-GP2 IgG in coprofiltrates in children of comparison group were 1.99 (1.26-3.04) U/ml; in the patients with CD, 23.5 (16.15-29.3) U/ml, and in children with UC, 20.45 (13.63-25.5) units/ml (p < 0.001). The cut-off value amounted 8.0 U/ml, with 100% sensitivity and 100% specificity. Concentrations of anti-GP2 IgA in coprofiltrates of patients with IBD did not significantly differ from DB patients. Moreover, the concentration of sIgA in the coprofiltrates of patients with IBD was significantly higher than their level in DB group. The anti-GP2 IgA/sIgA ratio was significantly lower in patients with CD (0.326 (0.23-0.512)), and UC (0.327 (0.205-0.435)), than in patients with DB (2.332 (1.575-3.523)) (p < 0.001); the cut-off level was 0.784, with a sensitivity of 97.7% and specificity of 98.6%. It is discussed, whether fecal anti-GP2 IgA antibodies should be considered as protective, supporting intestinal homeostasis, whereas anti-GP2 IgG antibodies are pathogenetically significant for development of IBD. Thus, using a non-invasive method for determining anti-GP2 antibodies in stool, when exceeding the cut-off for IgG, and reduction of IgA/sIgA ratio below the cut-off, one may differentiate IBD from DB with a similar symptoms at the onset of disease, with 100% sensitivity and 100% specificity.

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Section: Diagnostic Value Of Anti-gp2 Antibodies Determined In Serum unclassified

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Diagnostic value of anti-GP2 antibodies determined in serum and coprofiltrates in children with inflammatory bowel disease

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Evaluation of the functional activity of CD39 ectonucleotidase in regulatory T cells in children with inflammatory bowel diseases

et al. 2023

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In connection with the increasing incidence and prevalence of inflammatory bowel disease (IBD), the search for prognostic markers of the effectiveness of therapy is an urgent problem. An imbalance between Th17 lymphocytes and regulatory T cells (Treg) is a major defect in the immune system leading to IBD. Extracellular ATP produced during tissue damage, rebound pro-inflammatory effects, and activates Th17 cell differentiation. Ectonucleotidase CD39 catalyzes the dephosphorylation of ATP to AMP, followed by conversion to adenosine by CD73. CD39 is expressed in various cell types, including Treg. Aim – evaluate the functional activity of CD39+ in Treg in children with IBD using the luciferin-luciferase method.68 children with IBD were examined. Of these, 28 children were in remission, 40 were in exacerbation. The number of Tregs (CD4+CD25highCD127low) expressing CD39 was estimated by flow cytometry. The ATP concentration in supernatants and cells was determined using the luciferin-luciferase test. Results are presented as median (Me) and quartiles (Q0.25-Q0.75). The significance of differences between groups was assessed using the nonparametric Mann–Whitney U test.The relative number of CD39+Treg in patients in remission of IBD was significantly higher than in patients in a state of exacerbation. A decrease in ATP concentration under the influence of CD39+Treg in patients with IBD occurred immediately upon the addition of exogenous ATP. ATP in patients in remission decreased by 44.5% (Me 54.5 (41.5-65.9)), in patients in exacerbation – by 32.5% (Me 67.5 (59.7-71.3)). At the same time, in patients in remission, the decrease in the ATP content after 5 minutes of the reaction was significantly higher than in patients in the state of exacerbation (p = 0.01), after 30 minutes of the reaction, no significant difference was found. It was shown that samples with a smaller number of cells and a lower intensity of CD39 expression in Treg had a higher activity of CD39 ectonucleotidase.For efficient ATP hydrolysis, in addition to the amount of CD39 in Treg, their functional activity is important. The assessment of the catalytic activity of CD39 in Treg in patients with IBD is most informative in the first minutes after the addition of exogenous ATP. In patients in remission, the catalytic activity of CD39 in Treg was higher than in patients in a state of exacerbation.

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Content of CD4+ cells expressing CD39/CD73 ectonucleotidases in children with inflammatory bowel diseases

Радыгина

Petrichuk

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et al. 2022

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The regulation of TNF inhibitor therapy-associated immune responses in inflammatory bowel diseases (IBD) in children remains an urgent problem. The study aimed at analyzing the expression of CD39/CD73 endonucleotidases by different subsets of peripheral blood T cells in children with IBD including Crohn's disease (n = 34) and ulcerative colitis (n = 33) having received TNF inhibitors in comparison with conditionally healthy children (n = 45). Lymphocyte subsets including regulatory T cells (Treg, CD4+CD127lowCD25high), activated T cells (Tact, CD4+CD25+CD127high) and Th17 cells (CD4+CD161+CD3+) were studied by flow cytometry. The results are presented as medians (Me) and quartiles (Q25–Q75). In children with IBD the highest and the lowest relative counts of CD39+ cells were found in Treg and Tact subsets — 31% (15–38) and 4% (1–7), respectively. The highest relative counts of CD73+ cells were found in Tact — 13% (8–21). The CD39 and CD73 expression ratio in patients with IBD, and in the control group as well, depended on particular subset. CD39 expression in Treg, Tact and Th17 of patients with IBD was not age-dependent. Patients with acute Crohn's disease revealed decreased expression of CD39 in Treg compared with the control group (12% (9–23) vs 35% (28–39), respectively; р = 10–6). Patients with Crohn's disease in remission revealed increased expression of CD39 in Treg compared with the acute of the disease (31% (27–40) vs 12% (9–23); р = 9.4 × 10–5). Patients with Crohn's disease in remission revealed no significant differences with the control group apart from reduced expression of CD73 by Treg in Crohn's disease. The results indicate significant association of CD39 and CD73 expression levels in particular subsets of CD4+ cells with the phase of the disease (acute vs remission) and, accordingly, with the anti-TNF regimen efficacy.

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INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE

Cited by 3 publications

References 24 publications

Diagnostic value of anti-GP2 antibodies determined in serum and coprofiltrates in children with inflammatory bowel disease

Diagnostic value of anti-GP2 antibodies determined in serum and coprofiltrates in children with inflammatory bowel disease

Evaluation of the functional activity of CD39 ectonucleotidase in regulatory T cells in children with inflammatory bowel diseases

Content of CD4+ cells expressing CD39/CD73 ectonucleotidases in children with inflammatory bowel diseases

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