Treatment of severe juvenile idiopathic arthritis (JIA) represents a serious challenge. This study investigates the efficacy and safety of repeat courses of rituximab in patients with different forms of JIA refractory to infliximab and standard immunosuppressive therapy. Patients (n = 55; age 2.3-17.0 years) with severe polyarticular and systemic JIA (International League of Association for Rheumatology diagnostic criteria) received rituximab (one intravenous infusion/week for 4 weeks, 375 mg/m(2) per dose). Efficacy was assessed using the American College of Rheumatology Pediatric (ACR Pedi) criteria. The primary endpoint was an ACR Pedi 30 response at week 24. At week 24, ACR Pedi 30, 50, and 70 responses were achieved by 98%, 50%, and 40% of patients, respectively. By week 96, ACR Pedi 30, 50, and 70 responses were achieved by 98%, 93%, and 93% of 25 patients, respectively. Remission was recorded in 25%, 52%, 75%, and 98% of patients following the first (24 weeks), second (48 weeks), third (72 weeks), and fourth (96 weeks) courses of rituximab, respectively. Rituximab treatment significantly reduced the number of systemic manifestations at week 12 and also enabled 52% of patients to achieve remission of arthritis by week 48. This study supports the efficacy of rituximab in patients with severe forms of JIA, refractory to several prior agents.
Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by immune reactivity against microbial and auto-antigens. This work was designed to study the cytokine profile in blood serum and coproextracts of children with CD and UC. The studied patients consisted of 17 children with CD (group I), 17 children with UC (group II), and 18 controls with intestinal dysbiosis (group III). The diagnosis of UC and CD was based on accepted clinical and endoscopic criteria. The levels of 13 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-17A, TNF-α, TGF-β, and IFN-γ) were determined in blood sera and coproextracts of the patients and controls using the BioPlex technology. The level of IL-17A was significantly increased and that of TGF-β was significantly decreased in the blood serum of the patients with IBDs. Changes in the cytokine profile in the coproextracts affected the wider spectrum of cytokines. The levels of proinflammatory cytokines (IL-2, IL-4, IL-6, IL-12p70, TNF-α, and IFN-γ) were increased 6-9-fold, whereas the level of the anti-inflammatory cytokine IL-10 was increased 3-fold. The cytokine balance was shifted to the proinflammatory cytokines. The TGF-β level was increased 9-fold and that of IL-17A was increased 3-fold. Thus, the cytokine profile in the coproextracts was more informative than that of the blood serum. The determination of cytokines in coproextracts is simple and noninvasive.
60 children aged 1-2 years old (32 boys and 28 girls) were vaccinated with Priorix. Vaccinated children included healthy control (19 children, group 1), and children with immunological disturbances such as episodes of respiratory infection. From the latter group, 20 children did not receive (group 2), and 21 children received 0.15 mg/kg of Polyoxidonium simultaneously with the vaccine (group 3).On days 7 and 30 after vaccination, CD-markers on lymphocytes and concentration of specific antibodies, as well as levels of 11 cytokines in serum were evaluated by flow cytometry, ELISA, and multiplex techniques respectively. It was found that injection of Polyoxidonium skewed T helper differentiation to Th2 type. Antibody responses were significantly higher in children with preferable Th2 responses. Children from group 3 possessed higher titers of specific IgG-antibodies. Our study shows that Polyoxidonium could smooth out the immune reaction on vaccination. It is important for children with some immunological disturbances.
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