Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 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.
 ...
PMID:Case report: distinctive immune abnormalities in a patient with procainamide-induced lupus and serositis. 137 40

By means of a sensitive double-antibody radioimmunoassay, cachectin/tumour necrosis factor-alpha (TNF) was measured in sera from 51 patients with rheumatic disease. Elevated levels of circulating cachectin/TNF were observed in 46% of patients with rheumatoid arthritis (RA; p less than 0.001 versus blood donors) and in 29% of patients with systemic lupus erythematosus (SLE; p less than 0.05 versus blood donors). Marked elevation of cachectin/TNF occurred in both RA and SLE patients in connection with severe infections. The results show that cachectin/TNF is present in the circulation of certain patients with rheumatic disease, and that although the median cachectin TNF level in SLE patients is lower than that in RA patients, the cachectin/TNF response in SLE patients to severe infections is similar to that in RA patients.
 ...
PMID:Cachectin/tumour necrosis factor-alpha in the circulation of patients with rheumatic disease. 263 28

Levels of tumor necrosis factor/cachectin (TNF alpha) assessed by ELISA were similar in the supernatant of cultures from peripheral blood mononuclear cells (PBMC) from either active or inactive systemic lupus erythematosus (SLE) patients and controls stimulated with mitogen alone. When PBMC were stimulated with mitogen plus phorbol 12-myristate-13-acetate (PMA), the amount of TNF alpha was significantly decreased in culture supernatants from active patients or from the entire group of SLE patients studied. However, spontaneous synthesis of TNF alpha in nonstimulated cultures was increased in the SLE patients. Interferon-gamma (IFN-gamma) enhanced TNF alpha synthesis in cultures from either SLE patients or controls stimulated by concanavalin A (Con A) alone, but depressed the high production of TNF alpha by normal PBMC stimulated with Con A plus PMA. IFN-gamma enhanced TNF alpha production in response to Con A plus PMA in 2 of 3 SLE patients.
 ...
PMID:Production of tumor necrosis factor/cachectin by peripheral blood mononuclear cells in patients with systemic lupus erythematosus. 279 23

In view of recent data demonstrating defective production of tumor necrosis factor alpha (TNF cachectin) in murine autoimmune lupus nephritis, we studied the serum levels of TNF in 22 patients with systemic lupus erythematosus (SLE), using a specific radioimmunoassay. Patients with SLE had either normal or slightly elevated levels of TNF when compared with healthy control subjects. All 5 SLE patients with concomitant infections had elevated levels of TNF; those with systemic bacterial infection had markedly raised levels (median 260 pg/ml; normal less than 40). These results show that SLE in humans is not associated with a depressed level of circulating TNF, and that in SLE patients with infection, the level of TNF in the circulation increases in a manner similar to that in other subjects.
 ...
PMID:Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. 292 50

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.
 ...
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].
 ...
PMID:[Biologics-Induced Kidney Injury -with Special Attention to Anti-Rheumatic Drugs -]. 3069 31