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Poster presentations: Clinical: Therapy and Observation 2020

P423 NF-kB as a prognostic marker of response to biologic therapy in children with IBD

T. Radigina1, A. Illarionov2, D. Kuptsova1, A. Potapov3, S. Petrichuk1, A.P. Fisenko1

1National Medical Research Center for Children’s Health, Laboratory of Experimental Immunology and Virology, Moscow, Russian Federation, 2Pediatrics and Rheumatology, Sechenov First Moscow State Medical University, Moscow, Russian Federation, 3Gastroenterology and Hepatology, National Medical Research Center for Children’s Health, Moscow, Russian Federation

Background

The transcription factor NF-kB is a regulator of innate and adaptive immunity through the activation of various pro and anti-inflammatory mediators. The aim of this study was to assess the prognostic value of changes in the level of NF-kB translocation in lymphocyte populations in response to infusion of TNF blockers in children with IBD.

Methods

There were examined 44 children with IBD (27-CD, 17-UC) and 20 conditionally healthy children aged 3–18 years. Patient status (exacerbation, remission) was assessed by the PUCAI (UC) and PCDIA (CD) indices. There were determined the percentage of cells with NF-kB translocation in populations CD3+CD4+ (Th), CD3+CD8+(Tc), CD3-CD19+ (B cells), CD3-CD16 / 56+(NK cells), CD3+CD4+CD161+ (Th17), CD3+CD4+CD25highCD127low (Tregs) with NF-kB translocation kit using flow cytometry ImageStreamX MKII (Amnis) before infusion of TNF blockers (infliximab, adalimumab), one day after infusion and after 6 months therapy. Statistical evaluation was performed using a nonparametric Mann–Whitney test. The results are presented as the median per cent of cells with NF-kB translocation (Me [Q 0.25-Q 0.75]).

Results

It was observed an increased level of NF-kB translocation in B-lymphocytes (Me 64 [53–81] – Me 38 [33–45]; p = 6 × 10−5), NK cells (Me 40 [33 -55] – Me 21 [18–26]; p = 4x10-4), Tc (Me 20 [15–24] – Me 16 [13–17]; p = 0.03), Th17 (Me 23 [21–28] – Me 18 [16–19]; p = 0.005) in children with exacerbation compared with remission. The level of NF-kB translocation in populations of lymphocytes during the period of clinical endoscopic remission did not differ from conditionally healthy children. The correlation between the level of NF-kB translocation and the number of cells in the studied lymphocyte populations was not found. In children with IBD after infusion of TNF blockers, a decrease the level of NF-kB translocation in NK cells was observed (Me 27.3 [23.5–39.1] – Me 17.7 [16.5–26.5]; p = 0,03) and an increase in Tregs (Me 18.9 [16.91–20.8] – Me 26.9 [19.4–31.9]; p = 0.0015).

Conclusion

The level of NF-kB translocation reflects the functional activity of major and small populations of lymphocytes. An increase in activity of Tregs in response to the administration of TNF blockers allows predicting a positive outcome from therapy over the next 6 months. If there is no Tregs reaction in response to the administration of TNF blockers, treatment tactics should be reassessed.