Objective. Anti-CD20-mediated B cell depletion with rituximab is a new and effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral blood (PB) are consistently depleted in all patients, the clinical effects are more heterogeneous, possibly related to differences in the depleting effects of lymphoid or solid tissues. The aim of this study was to investigate B cell depletion in different compartments (PB, bone marrow, and synovium) and determine predictive variables for responsiveness to rituximab therapy.Methods. Before and 12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were collected from 25 patients with RA refractory to disease-modifying antirheumatic drugs and tumor necrosis factor-blocking agents. CD19؉ and CD20؉ B cells in PB and bone marrow were measured by flow cytometric analysis, whereas CD79a؉ and cytoplasmic CD20؉ B cells in the synovium were stained by immunohistochemistry. The effects of rituximab on serum Ig and autoantibodies were measured by enzyme-linked immunosorbent assay.Results. Rituximab effectively depleted the CD20؉ subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab significantly reduced autoantibody production (anti-citrullinated pro- Conclusion. These data provide novel insights into the mechanisms of CD20-mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.
Background and Objectives: Colonization of Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients may lead to severe pulmonary disease and death. Different characteristics of P. aeruginosa from these patients were determined in the present study. Materials and Methods: Antimicrobial susceptibility and AmpC-overproduction were determined. The β-lactamase genes were detected by PCR and the oprD gene was sequenced in some of the carbapenem resistance isolates. Distribution of exo genes was determined by PCR. Cytotoxicity of Exo effector proteins was measured using A549 cells. Biofilm production was determined by microtiter plate assay. Random amplified polymorphic DNA (RAPD) –PCR was performed for molecular analysis. Results: Polymyxin B, piperacillin/tazobactam and meropenem were the most active antibiotics and 9.6% of isolates were ampC overproducers. The prevalence of bla , bla , bla , and bla genes were as follow: 22.7%, 3.75%, 6.25% and VEB OXA VIM PER 3.75%, respectively. A high proportion (83.5%) of isolates was able to produce biofilm. The exoT gene was present in all isolates while exoU was present in about 35% of them. RAPD-PCR revealed 49 patterns among 78 tested isolates in which 34 patterns were detected once. Conclusion: Biofilm formation ability and relatively high frequency of exoS may contribute to the persistence of bacteria within lungs of CF patients. Some characteristics of isolates recovered from a single patient after several sampling proce- dures were similar, while others lacked resemblance.
Background: Frequent blood transfusion can lead to iron overload which is potentially dangerous for the heart and liver. Silymarin has well-documented protective effects on hepatocytes. The purpose of this study was to evaluate the hepatoprotective effects of silymarin addition to iron chelators in children with thalassemia. Materials and Methods: This randomized, double-blinded, and placebo-controlled trial was performed on 40 subjects with thalassemia major and intermedia in Amir Kabir Hospital, Arak, Iran. Subjects were randomized 1:1 oral to 30 mg/kg deferasirox plus placebo, or deferasirox plus oral 70-140 mg silymarin (twice daily) for 6 months. Cardiac and hepatic iron levels and levels of Gamma-glutamyltransferase (GGT), Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, albumin, total protein, and total cholesterol were measured at baseline and after 6 months of treatment. Results: The mean age of patients was 16 years and 60% of patients were female. After 6 months, there were significant increases in the levels of ALT, AST, GGT, and TG in the placebo group as compared to the silymarin group (P < 0.05). In contrast, ALT, AST, and GGT had significant reductions compared to the silymarin group (P =0.05). Patients in the placebo group had a rise in total bilirubin (P = 0.07), but total protein and albumin did not have significant changes in the silymarin group (P > 0.05). Finally, a significant improvement was noted in cardiac iron values in patients using silymarin; 22.2 ± 6.6 ms at baseline vs 26.9 ± 7.1 ms at 6 months (P < 0.05). Conclusion: This study suggests that twice-daily addition of silymarin to deferasirox could improve liver function in children with thalassemia major and intermedia. Silymarin seems safe in pediatrics.
Background/AimsInflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients.MethodsEighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated.ResultsFive patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed.ConclusionsA defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.
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