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

To gain insight into the immunopathogenesis of drug-induced autoimmune disorders, lymphocyte and immunoglobulin distributions and cytokine levels were monitored in the peripheral blood and pleural fluid of a patient with procainamide-induced lupus and pleural effusion. Approximately 80% of the B cells in both compartments were CD5+ compared to 10% to 25% in normal adults. CD4/CD8 ratio and percentage CD4 were normal in peripheral blood. Serum levels of IgG (particularly IgG2), IL-6, and soluble IL-2R were slightly elevated, and those of IgA were significantly elevated compared to normal controls. Analysis of the pleural effusion revealed an increased CD4/CD8 ratio because of an increased percentage of CD4+CD29+ helper memory T cells, lack of expression of the resting B-cell marker CD21, immune complex deposition and complement consumption, increased relative levels of ANA, abnormally high levels of IL-6 and soluble IL-2R, and detectable levels of IL-1b, IFN-g and TNF-a. These observations provide evidence for the involvement of CD5+ B cells and differential helper T-cell activity in procainamide-induced lupus and for an association between local lymphocyte activation and organ pathology.
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PMID:Case report: distinctive immune abnormalities in a patient with procainamide-induced lupus and serositis. 137 40

Immunologic cytotoxicity is an important endpoint of the immune response to tumors, viral infected cells, grafted tissues, and exogenous microorganisms, and is also an important mechanism of disease, especially in autoimmunity. There are multiple mechanisms of immunologic cytotoxicity, but each has three major stages: leukocyte/target attachment, specific recognition, and target lysis following effector activation. Adhesion molecules present on leukocytes and potential targets appear to be involved in all three stages of cytotoxicity. A major factor in all types of cellular cytotoxicity is the interaction of LFA-1 on leukocytes and CAM-1 on targets. Modulation of ICAM-1 levels on target by the cytokines TFN-g, IL-1, and TNF-a is a major point of control of the susceptibility of targets to cytotoxicity by many different cytotoxic mechanisms. It also appears that modulation of the avidity of LFA/ICAM-1 binding is another important control point in modulating immunologic cytotoxicity. Cytokines also have important effects on immunologic cytotoxicity in ways other than adhesion molecule induction: effector priming to better respond to specific recognition signals, effector mobilization into tissue, and expansion of cytotoxic effector populations. ICAM-1 on the surface of epidermal keratinocytes and melanocytes is likely to greatly influence cytotoxic damage of these cells in diseases as photosensitive lupus erythematosus, lichen planus, erythema multiforme, and vitiligo. It has been found that the epidermal staining pattern for ICAM-1 in each of these diseases in distinctive and different in each disease. It is proposed that disease-specific induction of ICAM-1 by factors such as UVR and herpes-virus is an important determinant in triggering these skin diseases and in determining the pattern of disease.
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PMID:Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets. 225 27

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.
Lupus 2003
PMID:TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease. 1287 47

Treatment of systemic lupus erythematosus (SLE), a chronic inflammatory disease, involves the long-term use of immunosuppressive agents with significant side effects. New therapeutic approaches are being explored to find better treatment possibilities. In this study, age-matched female MRL/lpr mice were treated orally with a natural flavonoid astilbin. Astilbin administration started either at week 8 or week 12 of age though week 20. In the early treatment regimen, the treatment with astilbin reduced splenomegaly/lymphomegaly, autoantibody production and ameliorated lupus nephritis. Several serum cytokines were significantly decreased upon treatment including IFN-g, IL-17A, IL-1b, TNF-a and IL-6. Both spleen CD44 hi CD62L lo activated T cells and CD138+B220- plasma cells greatly declined. Furthermore, astilbin treatment resulted in decreased mitochondrial membrane potential in activated T cells and downregulated expression of the co-stimulatory molecules CD80 and CD86 on LPS stimulated B cells. Similar but less profound effectiveness was observed in the mice with established disease in the late treatment regimen. These results indicate that the natural product astilbin can mitigate disease development in lupus-prone mice by decreasing functional activated T and B cells.
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PMID:Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural Flavonoid Astilbin. 2586 37

A variety of anti-rheumatic drugs including biologics are currently used to treat rheumatoid arthritis (RA). These drugs, as well as RA itself, can cause kidney injury. RA may trigger mesangial proliferative glomeru- lonephritis (MesPGN), membranous nephropathy (N), thin basement membrane disease, and renal amyloi- dosis. As for anti-rheumatic drugs, non-steroidal anti-inflammatory drugs (NSAID) increase serum Cr lev- els due to a reduction of glomerular circulation, particularly in the presence of dehydration. Among disease- modifying anti-rheumatic drugs (DMARD), methotrexate as an anchor drug for RA rarely causes tubular ob- struction as a result of its crystallization, and bucillamine occasionally elicits IN. Calcineurin inhibitors induce vasoconstriction of the afferent arteries. Recently developed anti-rheumatic drugs, biologics, include biological inhibitors of TNF-a, IL6, and CD80/26. These can generally induce the remission of RA, while they have been reported to albeit uncom- monly trigger autoimmune renal disorders (AIRD). A recent meta-analysis identified a total of 29 cases with biologics-induced AIRD, 62% of who manifested AIRD within 12 months after treatment with biologics. AIRD cases were classified into 3 different groups: isolated autoimmune renal disorders (IARD, n =13), glo- merulonephritis with systemic vasculitis (GNSV, n= 12), and glomerulonephritis with lupus-like syndrome (GNLS, n=4). The IARD cases had 4 MesPGN, 4 MN, and 2 crescentic GN, while the GNSV cases had 8 crescentic GN and 3 purpura GN, and the GNLS cases had all MesPGN. To detect these renal disorders early in RA patients, urinalysis and serum Cr measurement should be peri- odically performed. New urinary biomarkers (L-FABP and Ngal) may be more sensitive for kidney injury. Notably, in RA patients receiving biologics, ANA, anti-dsDNA, and ANCA should also be tested at the base- line and regular intervals. [Review].
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PMID:[Biologics-Induced Kidney Injury -with Special Attention to Anti-Rheumatic Drugs -]. 3069 31