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

Abstract

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.

Oxidative stress and modification of blood proteins in children with inflammatory bowel diseases

“…В эксперименте по изучению влияния воздействия NO-генерирующих соединений на уровень АТФ в лимфоцитах показано, что в больших концентрациях NO приводит к снижению уровня внутриклеточной АТФ и увеличению -внеклеточной, что сопровождается повышением содержания 3-НТ в крови [26]. В аналогичных нашим исследованиям группах пациентов с ВЗК установлено, что с ростом тяжести ВЗК снижается активность АТФазы в CD39 T-лимфоцитах, что может приводить к накоплению внеклеточной АТФ и её токсическому воздействию на лимфоциты через сигналлинг DAMPs (damage associated molecular partens) [27]. Можно полагать, что подобные изменения биохимических процессов способствуют развитию аутоиммунных реакций при ВЗК у детей.…”