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Serum Immunoglobulin Levels (serum + immunoglobulin_level)
Selected AbstractsProlonged effects of short-term anti-CD20 B cell depletion therapy in murine systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 8 2010Kai W. Bekar Objective Although B cells are implicated in the pathogenesis of systemic lupus erythematosus, the role of B cell depletion (BCD) as a treatment is controversial, given the variable benefit in human disease. This study was undertaken to test the effects of BCD therapy in a murine lupus model to better understand the mechanisms, heterogeneity, and effects on disease outcomes. Methods (NZB × NZW)F1 female mice with varying degrees of disease severity were treated with an anti-mouse CD20 (anti-mCD20) antibody (IgG2a), BR3-Fc fusion protein (for BAFF blockade), or control anti-human CD20 monoclonal antibody (,10 mg/kg each). Tissue samples were harvested and analyzed by flow cytometry. The development and extent of nephritis were assessed by monitoring proteinuria (using a urine dipstick) and by immunohistochemical analysis of the kidneys. Serum immunoglobulin levels were measured by enzyme-linked immunosorbent assay. Results After a single injection of anti-mCD20, BCD was more efficient in the peripheral blood, lymph nodes, and spleen compared with the bone marrow and peritoneum of normal mice as well as younger mice with lupus. Since depletion of the marginal zone and peritoneal B cells was incomplete and variable, particularly in older mice with established nephritis, a strategy of sequential weekly dosing was subsequently used, which improved the extent of depletion. BAFF blockade further enhanced depletion in the spleen and lymph nodes. Early BCD therapy delayed disease onset, whereas BCD therapy in mice with advanced disease reduced the progression of nephritis. These effects were long-lasting, even after B cell reconstitution occurred, and were associated with a reduction in T cell activation but no significant change in autoantibody production. Conclusion The lasting benefit of a short course of BCD therapy in lupus-prone mice with an intact immune system and established disease highlights the validity of this treatment approach. [source] The X-box binding protein-1 transcription factor is required for plasma cell differentiation and the unfolded protein responseIMMUNOLOGICAL REVIEWS, Issue 1 2003Neal N. Iwakoshi Summary:, X-box binding protein-1 (XBP-1) is a transcription factor essential for plasma cell differentiation. XBP-1 transcripts are found at high levels in plasma cells from rheumatoid synovium and myeloma cell lines. Lymphoid chimeras deficient in XBP-1 have a profound defect in plasma cell differentiation, with few plasma cells in their periphery and severely reduced serum immunoglobulin levels. When introduced into B-lineage cells, XBP-1 initiates plasma cell differentiation. XBP-1 is also the mammalian homologue of the yeast transcription factor Hac1p, an important component of the unfolded protein response (UPR). The UPR allows cells to tolerate conditions of endoplasmic reticulum (ER) stress caused by misfolded proteins. Studies examining the relationship between plasma cell differentiation, XBP-1, and the UPR demonstrate that this novel signaling system is vital for plasma cell differentiation. Signals that induce plasma cell differentiation and the UPR cooperate via XBP-1 to induce terminal B-cell differentiation. Additionally, XBP-1 plays an important role in the regulation of interleukin-6 production, a cytokine essential for plasma cell survival. [source] Intrathoracic nontuberculous mycobacterial infections in otherwise healthy childrenPEDIATRIC PULMONOLOGY, Issue 11 2009Alexandra F. Freeman MD Abstract Background Nontuberculous mycobacterial (NTM) infection is typically associated with lymphadenitis in immune competent children, and disseminated disease in children with immune deficiencies. Isolated pulmonary NTM disease is seen in cystic fibrosis, and is increasingly recognized in immunocompetent elderly women, where it is associated with an increased incidence of cystic fibrosis transmembrane regulator (CFTR) mutations. Thoracic NTM infection has been reported rarely in otherwise healthy children. We aimed to determine whether otherwise healthy children with pulmonary NTM disease had immunologic abnormalities or CFTR mutations. Clinical presentations of five otherwise healthy children with pulmonary NTM were reviewed. Immunologic studies were performed including a complete blood cell count (CBC), flow cytometric lymphocyte phenotyping and IFN-gamma receptor expression, in vitro cytokine stimulation, and serum immunoglobulin levels. Mutational analysis was performed for CFTR. The children ranged in age from 12 months to 2.5 years at diagnosis. Four presented with new onset wheezing or stridor failing bronchodilator therapy. One child was asymptomatic. Endobronchial lesions and/or hilar lymph nodes causing bronchial obstruction were identified in all patients. Mycobacterium avium complex was cultured from four patients, and Mycobacterium abscessus from one patient. All patients were successfully treated with anti-mycobacterial therapy with or without surgery. No definitive immunologic abnormalities were identified. No clinically significant mutations were found in CFTR. Pulmonary NTM infection should be considered in otherwise healthy young children presenting with refractory stridor or wheezing with endobronchial lesions or hilar lymphadenopathy. It does not appear to be associated with recognized underlying immune deficiency or CFTR mutations. Pediatr Pulmonol. 2009; 44:1051,1056. ©2009 Wiley-Liss, Inc. [source] Effects of lysed Enterococcus faecalis FK-23 on allergen-induced serum antibody responses and active cutaneous anaphylaxis in miceCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2004T. Shimada Summary Background Our previous studies have presented evidence that lysed Enterococcus faecalis FK-23 (LFK), a lysozyme and heat-treated probiotic product, can inhibit allergen-induced local accumulation of eosinophils in mice. Objective The purpose of this experimental study was to evaluate the influence of orally administrated LFK on the host immune responses. Methods BALB/c mice were sensitized subcutaneously, and challenged intraperitoneally by cedar pollen allergen. Blood and spleen samples were collected after oral administration of LFK 60 mg/day for 21 days. The serum levels of total and allergen-specific IgE and IgG2a antibodies and the production of IL-4, IL-5 and IFN-, generated by allergen-stimulated cultured splenocytes were determined. Additionally, the effect of LFK on active cutaneous anaphylaxis (ACA) induced by ovalbumin (OVA) challenge in mice was measured after 28 days LFK treatment. Results No significant differences in serum immunoglobulin levels, as well as in cytokine production of splenocytes were observed between LFK-treated and control mice (P>0.05). There was, however, an increasing tendency of allergen-specific IgG2a level in mice after LFK treatment for 21 days compared with controls (P=0.060). Furthermore, the serum ratio of specific IgE to IgG2a was found to be significantly decreased in the LFK group (P=0.005). In addition, a significant inhibition of OVA-induced ACA reaction was observed in mice that had been fed for 28 days with LFK compared with control mice (P=0.008). Conclusion These results suggest that LFK shows an anti-inflammatory effect, which may be part of the mechanism for protection against IgE-mediated allergy. [source] | ||||||||||