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Inflammatory Disease Activity (inflammatory + disease_activity)
Selected AbstractsAntibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 3 2010Sean G. O'Neill Objective Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti,apolipoprotein A-I (anti,Apo A-I), anti,high-density lipoprotein (anti-HDL), and anti,C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. Methods IgG anti,Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. Results Serum levels of IgG anti,Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti,Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti,Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti,Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti,double-stranded DNA. Conclusion Persistent disease activity is associated with a significant increase in IgG anti,Apo A-I and anti-HDL in patients with SLE. [source] Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serumPROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2009H. Ulrich Scherer Abstract In several autoimmune disorders, including rheumatoid arthritis (RA), autoantibodies are thought to be the driving force of pathogenicity. Glycosylation of the Fc-part of human Igs is known to modulate biological activity. Hitherto, glycosylation of human IgG-Fc has been analyzed predominantly at the level of total serum IgG, revealing reduced galactosylation in RA. Given the pathogenic relevance of autoantibodies in RA, we wished, in the present study, to address the question whether distinct Fc-glycosylation features are observable at the level of antigen-specific IgG subpopulations. For this purpose, we have developed a method for the microscale purification and Fc-glycosylation analysis of anti-citrullinated peptide antibodies (ACPA). ACPA represent a group of autoantibodies that occur with unique specificity in RA patients. Their presence is associated with increased inflammatory disease activity and rapid joint destruction. Results indicate that ACPA of the IgG1 subclass vary considerably from total serum IgG1 with respect to Fc-galactosylation, with galactosylation being higher on ACPA than on serum IgG1 for some patients, while other patients show higher galactosylation on serum IgG1 than on ACPA. Using this method, studies can be performed on the biological and clinical relevance of ACPA glycosylation within RA patient cohorts. [source] Natalizumab dosage suspension: Are we helping or hurting?ANNALS OF NEUROLOGY, Issue 3 2010Timothy W. West MD The risk of developing progressive multifocal leukoencephalopathy increases with the duration of treatment with natalizumab. Planned dosage interruptions have been proposed as a means of decreasing cumulative risk. The clinical consequences of dosage interruption were evaluated in a single center cohort of natalizumab-treated patients. Medical records were reviewed for 84 patients identified with multiple sclerosis who received 12 or more infusions of natalizumab at an academic multiple sclerosis center. Eighty-one percent (68/84) underwent a dosage interruption, and 19% (16/84) had no interruption in natalizumab treatment. Of those with a treatment interruption, 27.9% (19/68) experienced a clinical relapse within 6 months of the suspension, whereas none of the patients with ongoing treatment experienced a flare during months 12 to 18 of treatment (p = 0.017, Fisher exact test). Survival analysis showed that Kaplan-Meier curves comparing dosage interruption to ongoing treatment diverged (p = 0.025). Median time from treatment interruption to relapse onset was 3 months. No clinical predictors associated with an increased risk of developing flares during dosage interruption were identified. Among the 19 patients who had a flare, 7 had severe flares, with a mean number of 16 Gad+ lesions on brain magnetic resonance imaging (range, 6,40). Their median Expanded Disability Status Scale at natalizumab interruption was 3.0 and increased to 6.0 during the flare (p = 0.0008). Natalizumab dosage interruption is associated with clinical flares and return of radiographic inflammatory disease activity. Some of these flares can be clinically severe, with a high number of contrast-enhanced lesions, suggesting a possible rebound of disease activity. Ann Neurol 2010;68:395,399 [source] Abnormal B-cell cytokine responses a trigger of T-cell,mediated disease in MS?ANNALS OF NEUROLOGY, Issue 4 2010Amit Bar-Or MD, FRCP Objective To study antibody-independent contributions of B cells to inflammatory disease activity, and the immune consequences of B-cell depletion with rituximab, in patients with multiple sclerosis (MS). Methods B-Cell effector-cytokine responses were compared between MS patients and matched controls using a 3-signal model of activation. The effects of B-cell depletion on Th1/Th17 CD4 and CD8 T-cell responses in MS patients were assessed both ex vivo and in vivo, together with pharmacokinetic/pharmacodynamic studies as part of 2 rituximab clinical trials in relapsing,remitting MS. Results B Cells of MS patients exhibited aberrant proinflammatory cytokine responses, including increased lymphotoxin (LT):interleukin-10 ratios and exaggerated LT and tumor necrosis factor (TNF)-, secretion, when activated in the context of the pathogen-associated TLR9-ligand CpG-DNA, or the Th1 cytokine interferon-,, respectively. B-Cell depletion, both ex vivo and in vivo, resulted in significantly diminished proinflammatory (Th1 and Th17) responses of both CD4 and CD8 T cells. Soluble products from activated B cells of untreated MS patients reconstituted the diminished T-cell responses observed following in vivo B-cell depletion in the same patients, and this effect appeared to be largely mediated by B-cell LT and TNF,. Interpretation We propose that episodic triggering of abnormal B-cell cytokine responses mediates ,bystander activation' of disease-relevant proinflammatory T cells, resulting in new relapsing MS disease activity. Our findings point to a plausible mechanism for the long-recognized association between infections and new MS relapses, and provide novel insights into B-cell roles in both health and disease, and into mechanisms contributing to therapeutic effects of B-cell depletion in human autoimmune diseases, including MS. ANN NEUROL 2010;67:452,461 [source] | ||||||||||