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P144. Laboratory predictors of the effectiveness of transplantation of allogeneic mesenchymal stromal cells of bone marrow in patients with ulcerative colitis

L. Lazebnik1, O. Knyazev1, A. Parfenov1, V. Sagynbaeva1, I. Trubitcyna1, P. Shcherbakov1, A. Konoplyannikov2

1Central Scientific Research Institute of Gastroenterology, Moscow, Russian Federation; 2Medical Radiological Research Center of Russian Academy of Medical Sciences, Obninsk, Russian Federation

Despite significant achievements in studying the pathogenesis of inflammatory bowel disease (IBD), no found explanation why in some cases pathogenetic therapy of IBD is effective, while others – no. Knowledge of the factors that predict response to therapy, allow more efficient use of the method of treatment.

Aim: To identify predictors of effective clinical response to transplantation of allogeneic mesenchymal stromal cells (MSCs) of bone marrow in patients with ulcerative colitis (UC).

Material and Methods: Systemic MSCs transplantation performed 44 patients with chronic continuous and chronic recurrent course of UC. They compared 2 groups of patients depending on the effect of transplantation of bone marrow MSCs. The analysis took into account sex, age of the patients, the duration and severity of illness, length of bowel injury, the average duration of receiving azathioprine before MSC transplantation, the index of clinical and endoscopic activity, initial levels of immunoglobulin (Ig) IgG, IgA, IgM, before and after 2 months MSC transplantation. Clinical and endoscopic activity of UC was assessed on Rachmilewitz index. In the serum before and after MSC transplantation (2 months) were determined by humoral immune status using test-systems “Protein contour” (St. Petersburg).

Results: Transplantation of MSCs in the complex anti-inflammatory therapy of UC was effective in 32 patients (72.7%) – recurrence within UC for 12 months of observation. Therapy was ineffective in 12 (27.3%). The average content of the Ig in both groups of patients (n = 44) before and after the introduction of MSCs, respectively, was: IgM – 1.6 g/l and 2.18 g/l; IgG – 11.2 and 14.8 g/l; IgA – 1.42 and 2.84 g/l. Increased the concentration of IgA (p < 0.05). The content of Ig in blood serum in patients where transplantation has a positive effect (n = 32), before the introduction of MSCs was: IgM – 1.5±0.04 g/l, IgG – 12.5±0.71 g/l, IgA – 2.2±0.8 g/l. In patients (n = 12), where the effect was short, initial level of IgG – 8.8±0.9 g/l, IgM – 1.3±0.01 g/l, IgA – 0.9±0.01 g/l (p < 0.05). The dynamics of humoral immunity and cytokine status after 2 months after transplantation also significantly different in these two groups. In patients with a positive effect reached the level of immunoglobulin's: IgG – 18.5±0.9 g/l, IgM – 2.5±0.1 g/l, IgA – 2.1±0.8 g/l, a group of patients, where the effect was short – IgG – 7.3±0.2 g/l, IgM – 1.4±0.01, g/l, IgA – 1.0±0.01 g/l (p < 0.05).

Between the clinical efficacy (index Rachmilewitz) after MSC transplantation after 2 months and baseline values level of IgG (r = −0.87, p < 0.001), IgA (r = −0.70, p < 0.001), IgM (r = 0.72, p < 0.001).

Conclusion: MSC transplantation is most effective in UC patients with initially elevated levels of immunoglobulins in the period of exacerbation.