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

Radygina TV1, Petrichuk SV1, Kuptsova DG1, Potapov AS1,2, Illarionov AS2, Anushenko AO1, Kurbatova OV1, Semikina EL1,2
About authors

1 National Medical Research Center for Children's Health, Moscow, Russia

2 Sechenov First Moscow State Medical University, Moscow, Russia

Correspondence should be addressed: Tatiana V. Radygina
Lomonosovsky prospekt, 2/1, Moscow, 119296, Russia; ur.liam@anigidarvt

About paper

Funding: the study was carried out on state assignment of the Ministry of Health of Russia, number АААА-А19-119013090093-2.

Acknowledgement: the authors thank all patients for participation and acknowledge the Gastroenterology Department with Hepatology Group of the National Medical Research Center for Children's Health and its collaboration.

Compliance with ethical standards: the study was approved by the Ethics Committee of the National Medical Research Center for Children's Health, Moscow (protocol № 6 dated June 11, 2019). The informed consent was submitted by all study participants.

Received: 2022-06-22 Accepted: 2022-07-16 Published online: 2022-07-31

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.

Keywords: children, lymphocyte subsets, CD4+ subsets, Treg, Th17, Tact, CD39, CD73, inflammatory bowel diseases