The content of memory T-cells in children with immune-mediated inflammatory disease with varying effectiveness of biological therapy

Introduction. Immune memory is a tool of the adaptive immune system that allows it responding quickly and effectively to repeated contact with an antigen. The role of memory cell populations in the recurrence and progression of immune-dependent diseases is shown.

Aim. To determine the trend in memory T-cell populations depending on the effectiveness of biological therapy (BT) in children with inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis (PS).

Materials and methods. Four hundred fifty children with immunosuppressive diseases (ISD) were examined during different periods of administration of biological drugs: IBD — 162 children (infliximab /adalimumab), MS — 116 children (interferon β1α — IFNβ1α), PS — 172 children (adalimumab). The effectiveness of BT was assessed using clinical activity indices and functional methods. Lymphocyte immunophenotyping was performed by flow cytometry to determine populations of CD4⁺ and CD8⁺ memory T-cell: central (TCM), effector (TEM), and terminally differentiated (TEMRA). Statistical data processing was carried out in the Statistica 16.0 program, using the Mann–Whitney U-test, Spearman correlation analysis (p < 0.05). In the SPSS version 25 software, ROC analysis was performed in the efficiency–inefficiency separation model.

Results. In all forms of pathology, changes in the content of memory T-cells have been established depending on the activity of inflammation. In IBD and PS patients, with an increase in the indices of disease activity, a decrease in the levels of CD4⁺ naive T-cells (TNAIVE) and an increase of TCM were detected. In MS patients with active foci, an MRI scan showed a decrease in the percentage of naive CD8⁺ T-cells (TcytNAIVE) and an increase in the population of CD8⁺ TEM. The content of TNAIVE populations decreased with age, and memory T-cells increased in patients with all the studied forms of pathology. In patients with BT efficacy, a high content of TNAIVE populations and a low content of TCM were found compared with the levels in patients with insufficient BT efficacy. Thresholds have been determined for IBD, MS, and PS patients, which make it possible to predict the effectiveness of BT. An increase in the levels of TNAIVE and TcytNAIVE makes it possible to predict the presence of a BT effect, an increase in the levels of TCM, CD4⁺ TEM, and CD8⁺ TEMRA make it possible to predict the absence or insufficient effect of BT.

Conclusion. The activity of the inflammatory process is reflected in the differentiation of populations of CD4⁺ and CD8⁺ memory T cells. With the effectiveness of BT, the number of TNAIVE increases with a decrease in the number of TCM and TEM in patients with immune-dependent diseases, regardless of the form of pathology and the drug used. Threshold values for memory T-cells populations make it possible to predict the effectiveness of BT.

Contribution:
Radygina T.V., Petrichuk S.V. — research concept and design of the study;
Radygina T.V., Petrichuk S.V., Kuptsova D.G., Kurbatova O.V., Potapov A.S., Murashkin N.N., Abdullaeva L.M., Freydlin E.V., Kuzenkova L.M. — collection and processing of material;
Radygina T.V. — writing the text;
Fisenko A.P., Semikina E.L. — editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: December 17, 2024
Accepted: January 30, 2025
Published: February 28, 2025

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