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P186. Mitochondrial activity of B-lymphocytes in children with IBD receiving infliximab

L. Miroshkina1, S. Petrichuk1, I. Samokhina1, E. Tsimbalova2, A. Potapov2, T. Izmaylova1, M. Venediktova2, G. Semenova1, M. Varichkina2, 1Scientific Centre of Children Health, Cytochemical laboratory, Moscow, Russian Federation, 2Federal State Budgetary Institution “Scientific Centre of Children Health”, Gastroenterology and Hepatology, Moscow, Russian Federation

Background

It is known that succinate dehydrogenase (SDH) activity reflects cell energetic supply. SDH activity measurement is widely used as a basic laboratory marker in mitochondrial functioning diagnostics. The aim of the study was to investigate SDH activity in circulating B-lymphocytes in children with IBD under infliximab therapy.

Methods

We studied 44 children with Crohn's disease (CD) and 26 patients with ulcerative colitis (UC) at the age from 10 to 18 years, who received infliximab for a long period. We investigated circulating lymphocytes SDH activity by quantitative cytochemical method, based on the n-nitrotetrazolium violet ability to form insoluble formazan granules during enzymic reduction with a help of flow cytometer Beckman Coulter FC500 (USA). Circulating B-lymphocytes subsets sizes were also assess by flow cytometry. Clinical effect of the therapy was assessed using pediatric Crohn's disease activity index and pediatric ulcerative colitis activity index. Control group included 40 age- and sex-matched practically healthy children. All statistical tests were performed using nonparametric criteria (Kolmogorov–Smirnov test).

Results

It was revealed that 60% of children with IBD before the first infliximab infusion had significant decrease of B-cells number compared with healthy children alone with reference range of SDH activity. B1-cells number was decreased (16% IBD children vs 36% healthy children) and their SDH activity was significant higher than in control group (153.6±6.9 c.u. vs 108.3±3.9 c.u.). The ration between B1- and B2-cells SDH activities characterized with 3 times B1-cells activity domination compared with control group (80% vs 20%). B-cells SDH activity and their number gradually decreased with increasing duration of the disease, mainly by virtue of the B2-cells parameters change. After the year of infliximab therapy it was observed significant B1-cells number augmentation in patients with nonsustained efficacy of the therapy (16% before 1 infusion vs 26.6% after 1 year). Moreover the period of infliximab tolerance development corresponded to B1-cells SDH activity augmentation. Patients with sustained infliximab therapy efficacy had higher B2-cells SDH activity compared with patients with nonsustained effect (113.0±3.2 c.u. vs 94.1±2.7 c.u.).

Conclusion

Children with IBD were characterized with increase SDH activity of circulating B1-lymphocytes. Patients with nonsustained effect of infliximab therapy demonstrated gradually circulating B1-cells number increase along with B2-cells mitochondrial activity depression. The period of infliximab tolerance development corresponded to B1-cells SDH activity augmentation.