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

(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 cou...

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Main Authors: S. V. Petrichuk, L. V. Miroshkina, E. L. Semikina, A. P. Toptygina, A. S. Potapov, E. G. Tsimbalova, T. V. Radygina
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2018-11-01
Series:Медицинская иммунология
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Online Access:https://www.mimmun.ru/mimmun/article/view/1640
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author S. V. Petrichuk
L. V. Miroshkina
E. L. Semikina
A. P. Toptygina
A. S. Potapov
E. G. Tsimbalova
T. V. Radygina
author_facet S. V. Petrichuk
L. V. Miroshkina
E. L. Semikina
A. P. Toptygina
A. S. Potapov
E. G. Tsimbalova
T. V. Radygina
author_sort S. V. Petrichuk
collection DOAJ
description (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.
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spelling doaj.art-bd5236eb49264d118e8246728a9edef02024-04-22T13:07:43ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2018-11-0120572173010.15789/1563-0625-2018-5-721-7301046INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASES. V. Petrichuk0L. V. Miroshkina1E. L. Semikina2A. P. Toptygina3A. S. Potapov4E. G. Tsimbalova5T. V. Radygina6National Medical Research Center of Children’s Health.National Medical Research Center of Children’s Health.National Medical Research Center of Children’s Health; Russian National N. Pirogov Research Medical University.G. Gabrichevsky Research Institute for Epidemiology and Microbiology; M. Lomonosov Moscow State University.National Medical Research Center of Children’s Health.National Medical Research Center of Children’s Health.National Medical Research Center of Children’s Health.(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.https://www.mimmun.ru/mimmun/article/view/1640we have performed a study of blood lymphocyte subsets in children with inflammatory bowel disease
spellingShingle S. V. Petrichuk
L. V. Miroshkina
E. L. Semikina
A. P. Toptygina
A. S. Potapov
E. G. Tsimbalova
T. V. Radygina
INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
Медицинская иммунология
we have performed a study of blood lymphocyte subsets in children with inflammatory bowel disease
title INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
title_full INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
title_fullStr INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
title_full_unstemmed INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
title_short INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
title_sort indiсators of the lymphocyte subsets as efficiciency predictors of therapy with inhibitors of tnfα in children with inflammatory bowel disease
topic we have performed a study of blood lymphocyte subsets in children with inflammatory bowel disease
url https://www.mimmun.ru/mimmun/article/view/1640
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