Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B cell life depends critically on the cytokine B cell-activating factor of the tumor necrosis factor family (BAFF). Lack of BAFF signaling leads to B cell death and immunodeficiency. Excessive BAFF signaling promotes lupus-like autoimmunity. Despite the great importance of BAFF to B cell biology, its signaling mechanism is not well characterized. We show that BAFF initiates signaling and transcriptional programs, which support B cell survival, metabolic fitness, and readiness for antigen-induced proliferation. We further identify a BAFF-specific protein kinase C beta-Akt signaling axis, which provides a connection between BAFF and generic growth factor-induced cellular responses.
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PMID:BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism. 1706 Apr 74

CD30/CD30L and CD40/CD40L are molecules from the tumor necrosis factor (TNF) superfamily. They have a major effect on communications between the B and T cells, which leads to control of maturation, proliferation, and apoptosis of those cells. The aim of this study was to compare the levels of a soluble form of CD30 (sCD30) and a soluble ligand CD40 (sCD40L) in patients with systemic lupus erythematosus (SLE) (n=65) and healthy controls (sCD30 n=20, sCD40L n=10) with other parameters of SLE activity. Patients were divided into subgroups according to presence or absence of lupus nephritis (LN; 33 with LN, 32 without LN). The serum levels of selected parameters were assessed also in the subgroups with low active disease characterized by European Lupus Activity Measure (ECLAM) at most 3(n=29) and active disease with ECLAM more than 3 (n=36). The serum levels of sCD30 were 66.0+/-40.2 UI/ml in the whole group. The mean serum levels were 60.0+/-45.2 UI/ml in the subgroups with LN, 67.1+/-38.9 UI/ml in the subgroup without LN, 80.2+/-51.9 UI/ml in the subgroup with active disease, 55.4+/-24.1 UI/ml in the subgroup with low active disease, and finally, 40.1+/-19.2 U/ml in the controls. Significant differences were found between the SLE patients and controls (p=0.0001) and between the active and nonactive groups (p=0.002). A correlation was found between levels of CD30 and ECLAM (r=0.25, p<or=0.05), SLEDAI (SLE Disease Activity Index) (r=0.25, p<or=0.05), C4 component of the complement system (r=0.24, p=0.02), and anti-C1q antibodies (r=0.42, p=0.0001). The levels of sCD40L were 7.4+/-6.7 ng/ml in whole SLE group, 7.0+/-8.1 ng/ml in the subgroup with LN, 8.0+/-4.9 ng/ml in the subgroup without LN, 7.1+/-5.0 ng/ml in the group of patients with active disease, 7.73+/-7.8 ng/ml in the subgroup with low activity, and 2.96+/-1.39.0 ng/ml in the controls. The difference in sCD40L serum levels between patients with SLE and controls was statistically significant (p=0.02). A correlation was found with the anti-C1q antibodies (r=0.21, p=0.05); no other correlations were found. These findings indicate some potential role of both serum parameters in measurement or SLE disease activity, although their usage in the diagnostic of disease requires further investigation.
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PMID:The levels of sCD30 and of sCD40L in a group of patients with systemic lupus erythematodes and their diagnostic value. 2752 Jul 3

The concept of biological therapy arises from the specific targeting of a factor, e.g. a cytokine, involved in the inflammatory cascade. Thus, biologicals disrupt the complex network of autoimmune-inflammatory events. Today, rheumatoid arthritis is a prototype disease in this context as most compounds have been tried in this disease. Recently, biological therapy has been introduced to the treatment of other diseases including various forms of arthritis, such as ankylosing spondylitis and psoriatic arthritis, as well as systemic autoimmune disorders, such as systemic lupus erythematosus, scleroderma, inflammatory myopathies and Sjogren's syndrome. Anti-tumor necrosis factor-alpha (TNF-alpha) agents play a central role in biological therapy as these agents have been successfully tried in most of these diseases. When seeking for specific targets for biologicals, pathogenic factors of the disease, such as Th1 or Th2 type responses, should be evaluated. Some mostly T-cell mediated diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, polymyositis, polyarticular juvenile arthritis respond well to anti-TNF agents and T cell targeting, while others, such as lupus, Sjogren's syndrome, dermatomyositis may rather respond to anti-B cell biologicals. In this review, authors discuss the most recent advances in the biological therapy of arthritis and systemic autoimmune diseases including issues of efficacy and safety.
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PMID:[Biological therapy of arthritis and systemic autoimmune diseases]. 1743 Jul 97

Certolizumab pegol is a pegylated humanized Fab' fragment of an anti-tumor necrosis factor-alpha (TNFalpha) monoclonal antibody, which binds with high affinity to both membrane-bound and soluble TNFalpha and demonstrates high neutralizing potency for these factors. The elimination half-life of certolizumab in humans has been extended to approximate/= 2 weeks through pegylation, allowing subcutaneous administration of this agent once every 4 weeks. Subcutaneous certolizumab pegol 400mg once every 4 weeks (with an additional 400mg dose at week 2) was effective as induction and maintenance therapy in patients with moderate to severe Crohn's disease in whom baseline serum C-reactive protein levels were >/=10 mg/L, according to data from two well designed, randomized phase III trials. Certolizumab pegol was, in general, well tolerated, and adverse events associated with the drug were of a mild to moderate nature; no instances of lupus were reported in any of the trials.
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PMID:Certolizumab pegol: in Crohn's disease. 1751 14

During the last decade, the role of inflammation in the etiopathogenesis of arterial thrombosis has been elucidated. However, little is known about the relationship between inflammation and venous thrombosis. Recently, inflammation has been accepted as a possible mechanism through which different risk factors trigger thrombus formation in veins. The data indicate that inflammation of the vessel wall initiates thrombus formation in an intact vein and that inflammation and coagulation systems are coupled by a common activation pathway. The first event in thrombus formation is most probably activation of endothelial cells, platelets and leucocytes, with initiation of inflammation and formation of microparticles that trigger the coagulation system through the induction of a tissue factor. Therefore, the key event in the initiation of venous thrombus formation is most probably vein wall inflammation. However, expected relationship between inflammatory markers as indicators of inflammatory process and clinical venous thromboembolism (VTE) has not yet been elucidated. C-reactive protein does not appear to be useful in predicting future venous thrombosis or to be useful in the diagnosis of VTE. Recently, it was demonstrated that probable association between VTE and several other markers of inflammation such as: interleukin (IL)-6, IL-8 and tumor necrosis factor-a exists. While these markers of inflammation were studied during or after acute venous thrombosis, further prospective studies are needed to determine the predictive value of inflammatory markers for VTE. The identification and elucidation of inflammatory markers relevant to venous thrombosis could provide targets for future therapy. That inflammation is the basic etiopathogenetic process of VTE is also supported by the relation of some risk factors to both arterial and venous thrombosis: age, increased body mass index, hypercholesterolemia, hypertension, lupus anticoagulant and hyperhomocysteinemia. A relation was also found between preclinical and clinical atherosclerotic disease and VTE. Also in line with these arguments are the preventive effects of aspirin and statins in both arterial and venous disease.
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PMID:The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis. 1809 97

Autoantibodies and lupus-like syndromes can develop following the use of certain medications; however, although many patients develop autoantibodies, only a minority develop clinical features. Although these autoantibodies primarily consist of antinuclear and antihistone antibodies, additional types of antibody, such as antineutrophil cytoplasmic antibodies and anti-double-stranded DNA antibodies, have been reported in association with minocycline and tumor necrosis factor inhibitor therapy. Clinical features of drug-related lupus usually consist of constitutional symptoms, arthralgias, arthritis, myalgias and serositis, although cutaneous manifestations have been reported in association with the use of tumor necrosis factor inhibitors. Typically, clinical features resolve with discontinuation of the medication, although antibodies can persist for months or years. Arthralgias and inflammatory arthritis have also been reported in association with the use of aromatase inhibitors and other biologic agents such as interleukins and interferons.
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PMID:Drug insight: autoimmune effects of medications-what's new? 1820 8

The concurrence of ankylosing spondylitis (AS) in a patient with mixed connective tissue disease (MCTD) is rarely described in the literature. Significant and sustained efficacy with tumor necrosis factor (TNF)-alpha blockers has been demonstrated in AS patients. However, evidence to date has revealed associated side effects, including antinuclear antibody induction and development of a lupus-like syndrome. Several authors have reported lupus-like manifestations in MCTD patients treated with TNF-alpha blockers used to control peripheral polyarthritis. In our case report, we demonstrate a good response to etanercept therapy for refractory sacroiliitis in a patient with coexisting AS and MCTD, without development of a lupus-like syndrome. This demonstrates that etanercept therapy may be an appropriate therapeutic agent for sacroiliitis in MCTD patients, as it is in AS alone.
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PMID:Successful etanercept therapy for refractory sacroiliitis in a patient with ankylosing spondylitis and mixed connective tissue disease. 1830 84

Leflunomide is an immunosuppressive agent that acts by inhibiting pyrimidine synthesis in lymphocytes and other rapidly proliferating cells, as well as by suppressing tumor necrosis factor-alpha-induced cellular responses. A number of leflunomide-related adverse events have been reported. Among cutaneous side effects, a few cases of subacute cutaneous lupus erythematosus have been described. We report a previously undocumented reaction to leflunomide, manifesting as subacute cutaneous lupus erythematosus and erythema multiforme-like lesions, in a young woman treated with this drug for ankylosing spondylitis. Withdrawal of leflunomide combined with a short cycle of systemic corticosteroid led to the resolution of the patient's rash, indicating this drug as being responsible for the development of the disease. We conclude that leflunomide might have triggered the occurrence of both subacute cutaneous lupus erythematosus and erythema multiforme in a patient with pre-existing autoimmune diathesis. The suppressive effect of this drug on tumor necrosis factor-alpha-related mechanisms might have played a role in the induction of such a unique reaction to leflunomide.
Lupus 2008 Apr
PMID:Leflunomide-induced subacute cutaneous lupus erythematosus with erythema multiforme-like lesions. 1841 15

Host responses to synthetic implants are analogous to healing, the process of repair that follows injury. Normally, the processes of wound healing follow well-established patterns but conditions such as autoimmune diseases profoundly affect tissue repair. We have analyzed sponge-induced wound healing responses in lupus-prone New Zealand White and control (Balb/c) mouse strains by measuring inflammation, extracellular matrix deposition, angiogenesis, and cytokine production in polyether-polyurethane sponge implanted subcutaneously in male mice of these two strains. Although there was no difference in the gross appearance of the implants, further analysis of the wound healing responses, induced from 7 to 21 days post implantation, disclosed important differences between the New Zealand White and Balb/c strains. The intensity of inflammation (circulating tumor necrosis factor-alpha and inflammatory leukocytes levels) was lower but implant fibrosis (collagen and transforming growth factor-beta1) was higher in New Zealand White, compared with Balb/c mice. Angiogenesis (hemoglobin, vascular endothelial growth factor, and vascularity) in New Zealand White implants peaked earlier than in Balb/c mice. In conclusion, we have shown that wound healing responses are clearly different in this strain of lupus-prone mice and suggest that this pattern of repair was critically influenced by impaired inflammation and accelerated angiogenesis in the New Zealand White strain.
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PMID:Mechanisms of wound healing responses in lupus-prone New Zealand White mouse strain. 1847 Dec 60

Over the last few years evidence on the major pathophysiological role of cytokines in system lupus erythematosus (SLE) has accumulated. Immunological results were recently confirmed by first clinical trials, which suggest that therapies targeted at the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, as well as the blockade of Interferon, may be highly effective. Controlled clinical trials will have to prove this concept over the next few years.
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PMID:[Cytokine blockade - a promising therapeutic option in SLE]. 1849 Nov 17


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