#2733 TRANSPLANTATION OF MESENCHYMAL STEM CELLS - NEW FOCUS OF IMMUNE CORRECTION IN TREATMENT OF LUPUS NEPHRITIS

Abstract

Abstract Background and Aims Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by the production of organ-specific autoantibodies to components of cell nucleus, immune complex lesions of the connective tissue, and the development of irreversible damage of internal organs. Chronic relapsing course of SLE, resistance to steroid and immunosuppressive therapy, toxic effects of drugs determine the need of search for new therapeutic approaches. Objective To evaluate the efficacy and safety of bone marrow mesenchymal stem cell (MSC) transplantation with high-dose immunosuppressive therapy (HIST) in SLE patients. Method A total amount of 15 patients with a diagnosis of SLE (ACR criteria) refractory to classical immunosuppressive therapy was examined. Patients were divided into 2 groups: patients from the main group underwent MSCs transplantation with HIST (n = 10), while the control group was observed on the background of traditional immunosuppressive therapy without cell transplantation (n = 5). Both groups were comparable in age, gender of patients, duration and severity of the disease. The SELENA-SLEDAI was used to determine SLE activity. Cytokines were examined by ELISA (IL-1Β, IL-4, IL-10, TNF-Α), antibodies to double-stranded DNA (anti-dsDNA) and anti-nuclear antibodies (ANA) by indirect immunofluorescence. Morphological examination of kidney included Masson-trichrome histochemistry for collagen fibers, silvering reaction for elastic and reticulin fibers, immunofluorescent and immunohistochemical methods. The safety assessment included registration of various adverse events during and after transplantation. Statistical analysis was carried out by Kruskal-Wallis test using STATISTICA 6.1. Results Monitoring the effectiveness of autologous stem cell transplantation in SLE patients showed a significant 2-fold decrease in activity by SELENA-SLEDAI score from 14.67±1.15 to 7.33±1.15 points after 12 months (p = 0.03). In the control group, this indicator remained unchanged and amounted to 15.0±0.87 points despite ongoing immunosuppressive therapy. Clinical efficacy was noted in all patients receiving HIST and MSC transplantation, which was confirmed by a significant decrease in daily proteinuria from 2,48±0,77 to 1,06±0,56 g/l, a decrease in the value of antibodies to DNA (from 443,28±547,53 to 187,8±146,60) and blood cytokines (significantly for TNF-Α), and an increase in the level of complement (though insignificantly). According to kidney biopsy data, after MSC transplantation with HIST, positive dynamics consisted in an increase in the number of reticulin fibers in the vascular loops of the glomeruli, as well as a decrease in the immune inflammatory process in the vascular loops of the glomeruli by immunofluorescence analysis for the spectrum of antibodies (Figure 1). In most patients of the main group, the doses of methylprednisolone and immune suppressants were reduced. Chills during transplantation was registered in one patient; no other unwanted adverse events were identified. Conclusion MSC transplantation in combination with HIST is significantly more effective than traditional immunosuppressive therapy in SLE according to clinical and laboratory data. The method is safe, allows decreasing signs of autoimmune aggression and can be used in cases of refractoriness, low efficiency or intolerance of standard therapy for SLE.