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The effects of the TNF-α blockers infliximab or etanercept on the levels of TNF-α, TNF-receptor 1 (TNF-R1), and TNF-receptor 2 (TNF-R2), as well as the levels of the inflammation markers CRP and IL-6, were measured in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients receiving treatment with either compound. We found that RA patients tend to have higher levels of TNF-α than both healthy individuals and AS patients prior to treatment (P<0.05). We measured greatly increased levels of TNF-α in both the AS and RA etanercept patient groups during the course of treatment, while in the infliximab treated patients, the amount of TNF-α measured remained unchanged. Elevated TNF-α in the etanercept treated patients does not appear to be a significant risk factor for the spontaneous development of further autoimmune diseases in our study group. Increased levels of TNF-R1 were determined in both AS (P<0.05) and RA (P<0.001) patients when compared to healthy controls. In AS patients, the levels of TNF-R1 dropped significantly when treated with either infliximab (P<0.01) or etanercept (P<0.001). In contrast, the levels of this receptor remained unchanged in RA patients treated with either compound.

The analysis of the molecular basis of autoimmune diseases is currently under intense investigation. The identification of novel mechanisms underlying the pathogenesis of these diseases generates the possibility for the development of new therapeutic agents. In this review we summarize the results leading to novel insights concerning the molecular processes involved in the pathogenesis of rheumatoid arthritis, systemic lupus erythematodes, multiple sclerosis and diabetes type 1. We focus on the role of transcription factors such as nuclear factor kappa B, activator protein 1, peroxisome proliferator-activated receptor, vitamin D receptor and the glucocorticoid receptor that mediate pro- and antiinflammatory effects and therefore represent direct or indirect targets for therapeutic intervention.

Background Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. Objectives To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). Methods The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. Results Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often ‘other antibodies’ (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. Conclusions These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.

The effects of the TNF-α blockers infliximab or etanercept on the levels of TNF-α, TNF-receptor 1 (TNF-R1), and TNF-receptor 2 (TNF-R2), as well as the levels of the inflammation markers CRP and IL-6, were measured in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients receiving treatment with either compound. We found that RA patients tend to have higher levels of TNF-α than both healthy individuals and AS patients prior to treatment ( P < 0.05 ). We measured greatly increased levels of TNF-α in both the AS and RA etanercept patient groups during the course of treatment, while in the infliximab treated patients, the amount of TNF-α measured remained unchanged. Elevated TNF-α in the etanercept treated patients does not appear to be a significant risk factor for the spontaneous development of further autoimmune diseases in our study group. Increased levels of TNF-R1 were determined in both AS ( P < 0.05 ) and RA ( P < 0.001 ) patients when compared to healthy controls. In AS patients, the levels of TNF-R1 dropped significantly when treated with either infliximab ( P < 0.01 ) or etanercept ( P < 0.0 0 1 ). In contrast, the levels of this receptor remained unchanged in RA patients treated with either compound.

The aim of this study was to analyse patients with ankylosing spondylitis (AS) during the course of infliximab therapy. The molecular effects were evaluated using lymphocytes and sera that were isolated before therapy began, then again after 2 and 12 weeks from 17 AS patients and compared to those of 24 healthy control individuals. All 17 AS patients responded to treatment with infliximab as assessed using BASDAI. Elevated serum levels of IL-6, CRP and cortisol were reduced to normal levels by the 12 weeks time point. The level of DNA-binding p65 was decreased during the course of infliximab therapy whereas the level of DNA-binding p50 remained elevated until the 12 weeks time point. Taken together, Infliximab is an effective treatment for AS and results in decreased levels of the inflammation markers IL-6 and CRP, and of endogenous cortisol concentration. Unequal alterations in the levels of activated NF-kappaB subunits p50 and p65 might provide insights into the mechanisms of NF-kappaB action and anti-TNF-alpha therapy in AS.

The aim of this study was to determine the activation level of the pro-inflammatory transcription factor nuclear factor κB (NF-κB) in lymphocytes of patients with rheumatoid arthritis (RA) before and during an anti-tumor necrosis factor α (TNFα) therapy (adalimumab). In addition, we analyzed the inflammatory markers, interleukin 6 (IL-6), and C-reactive protein (CRP) and investigated the expression of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies in patients' sera. Twenty RA patients and 20 control subjects were investigated. RA patients' characteristics were evaluated by radiography and disease activity score 28 (DAS 28). Twelve weeks of adalimumab therapy was effective in the treatment of RA patients, as shown by a significant improvement of the DAS 28. The inflammatory markers IL-6 and CRP were significantly different in sera of RA patients compared to the control group before the onset of therapy and exhibited a tendency to return to normal levels during the first 12 weeks of therapy. We measured a comparable activation level of NF-κB in lymphocytes of control subjects and of RA patients before starting adalimumab therapy. During the following 12 weeks, no significant changes in the activation levels of both NF-κB subunits were detected. Serum concentration of RF was significantly lower after 12 weeks, whereas anti-CCP antibody level remained constant.[PUBLICATION ABSTRACT]