Abstract
(IBD), who were for the first time treated with TNFα blocker (infliximab). Our aim was to determine prognostic informative value of the immunological parameters in order to assess the treatment efficiency. A comprehensive research included seventy children with IBD from 12 to 18 years old in the course of specific treatment (49 children with CD, 21 children with UC).The comparison group consisted of fifty healthy children of similar age who were subjected to a similar detailed examination. The patients were divided into two groups, depending on their therapeutic response following 1 year of biological therapy: the first group showed a persistent positive effect of the drug, and the second group exhibited only unstable effects of the treatment. We determined the contents of major and small subpopulations of peripheral blood lymphocytes before the first administration of infliximab. Immunophenotyping was performed by multicolor flow cytometry (FC 500), using the CD45, CD3, CD4, CD8, CD19, CD16, CD56, HLA-DR, CD5, CD161, CD127, CD25, and CD294 markers.We have revealed that the content of B lymphocytes was significantly reduced in children with unstable effects of therapy. By contrast, the B lymphocyte levels in children with persistent positive therapeutic effect did not differ from the comparison group. Analysis of the composition of the B lymphocyte profile showed an imbalance in the B1-to-B2 cell ratio, with decreased of B1 cell counts in IBD patients against the comparison group. In addition, the patients with unstable therapeutic effect showed a significant decrease in B2 cell numbers compared with a group with persistent effect and comparison group. The numbers of NK cells in IBD patients were found to be reduced against the comparison group. Assessment of T lymphocytes subsets revealed a number of features in the patients with minimal therapeutic effects, i.e., an increased level of activated T helper cells (CD4+CD25+CD127high) and Th17 lymphocytes (CD3+CD4+CD161+), as compared to children with stable effect of treatment and to the comparison group. Moreover, in children with minimal effects of therapy, the levels of Tregs within T-helper cell subsets were significantly higher than in the comparison group. By means of ROC analysis, we have identified most informative parameters for the groups with minimal versus persistent therapeutic effect, and showed a good quality for a discrimination model involving relative amount of Th17 cells, activated T helper cells and B lymphocytes. The number of Тh17 lymphocytes (% CD3+CD4+ lymphocytes) allowed to predict the effect of therapy with a TNFα blocker with high probability. The present study enables us to propose cellular immunity testing, as a promising tool for monitoring clinical state of IBD patients.
Highlights
В настоящее время полагают, что развитие хронического воспаления при воспалительных заболеваний кишечника (ВЗК) обусловлено дисрегуляцией нормального иммунного ответа на комменсальную микрофлору кишечника у генетически предрасположенных лиц
We have performed a study of blood lymphocyte subsets in children
who were for the first time treated with TNFα blocker
Summary
Петричук С.В.1, Мирошкина Л.В.1, Семикина Е.Л.1, 4, Топтыгина А.П.2, 3, Потапов А.С.1, Цимбалова Е.Г.1, Радыгина Т.В.1. Получено: содержание В-лимфоцитов было достоверно снижено у детей с нестабильным эффектом терапии, у детей со стойким положительным эффектом уровень В-лимфоцитов не отличался от группы сравнения. Анализ состава В-лимфоцитов показал дисбаланс в соотношении В1- и В2-клеток с уменьшением содержания В1-клеток у пациентов с ВЗК относительно группы сравнения. Количество NK-клеток у пациентов с ВЗК было снижено относительно группы сравнения. Радыгина «Показатели популяционного состава лимфоцитов как предикторы эффективности терапии ингибитором TNFα у детей с воспалительными заболеваниями кишечника» // Медицинская иммунология, 2018. Медицинская Иммунология Medical Immunology (Russia)/Meditsinskaya Immunologiya (CD3+CD4+CD161+) относительно детей со стойким эффектом терапии и группы сравнения. Petrichuk S.V.a, Miroshkina L.V.a, Semikina E.L.a, d, Toptygina A.P.b, с, Potapov A.S.a, Tsimbalova E.G.a, Radygina T.V.a a National Medical Research Center of Children’s Health, Moscow, Russian Federation b G.
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