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)

Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role.
 ...
PMID:Newer uses of glucose-insulin-potassium regimen. 1120 54

In systemic lupus erythematosus, plasma concentrations of tumor necrosis factor alpha (TNF alpha) and other pro-inflammatory cytokines are elevated and those of transforming growth factor beta (TGF beta) are decreased. TNF alpha prevents lupus nephropathy whereas increased concentration of TGF beta causes glomerulosclerosis. Insulin inhibits TNF alpha and enhances TGF beta production, augments nitric oxide synthesis and blocks superoxide anion generation. Polyunsaturated fatty acids (PUFAs) also have actions similar to insulin. Hence, it is suggested that a combination of insulin (in the form of glucose-insulin-potassium) and PUFAs may be of benefit in lupus and other inflammatory conditions.
 ...
PMID:Hypothesis: can glucose-insulin-potassium regimen in combination with polyunsaturated fatty acids suppress lupus and other inflammatory conditions? 1154 28

A number of studies reported associations of HLA-DRB1, TNFalpha (TNF) promoter and TNF receptor II (TNFR2, TNFRSF1B) polymorphisms with systemic lupus erythematosus (SLE), however, the results have often been inconsistent. Such lack of consistency could partly derive from the population admixture involved in the case-control study. To avoid such a problem, polymorphisms in these genes were analyzed using transmission disequilibrium test (TDT) in Caucasian SLE families. Ninety-one Caucasian SLE family samples recruited in southern California were analyzed for the association with HLA-DRB1, TNF promoter positions at -1031, -863, -857 and -308, and TNFR2-196M/R polymorphisms. Significant transmission was observed for HLA-DRB1*1501, but not for HLA-DRB1*0301, nor for TNF haplotype that codes for -308A. Interestingly, TNF haplotype coding for -1031C, -863A, -857C showed a tendency of preferential nontransmission in the patients without lupus nephritis and in those with malar rash. No transmission distortion was observed for TNFR2-196R allele. These findings confirmed the association of HLA-DRB1*1501, but did not replicate that of the HLA-DRB1*0301, TNFA-308A and TNFR2-196R with SLE in this population. In addition, a possible disease-protective role for TNF haplotype coding for -1031C, -863A, -857C was suggested.
 ...
PMID:Analysis of the association of HLA-DRB1, TNFalpha promoter and TNFR2 (TNFRSF1B) polymorphisms with SLE using transmission disequilibrium test. 1160 87

The major histocompatibility (MHC) genes including TNF-alpha, HSP70 and HLA genes have been associated with systemic lupus erythematosus (SLE) in several populations. In this study we analyze the polymorphism of TNF-alpha promoter in 51 Mexican Mestizo SLE patients and 55 ethnically-matched healthy controls by polymerase chain reaction methods. No statistically significant differences were observed in the TNF -308 allele and genotype distribution between patients and healthy controls. However, we found a significant increase in the TNF G/A -238 genotype and in the TNFA -238 allele frequencies in the SLE group when compared with healthy controls (Pc = 0.03, OR = 4.77 and Pc = 0.02, OR = 3.62, respectively). DRB1 analysis showed a similar distribution in patients and controls. Linkage disequilibrium was observed for five haplotypes: DRB1*1401-TNFA-238 (D = 0.84; D' = 1.0; P = 0.015); DRB1*0301-TNFA-238 (D = 1.38; D' = 0.41; P = 0.042); DRB1*1106-TNF2-308 (D = 0.9; D' = 1.0; P = 0.0006); DRB1*1104-TNF2-308 (D = 0.83; D' = 0.45; P = 0.02) and DRB1*1406-TNF2-308 (D = 0.83; D' = 0.45; P = 0.02). Our data suggest that the association between the TNF-alpha -238 polymorphism and SLE could play a major role in disease susceptibility.
 ...
PMID:Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). 1170 1

Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low levels of DPP IV and high titers of anti-DPP IV autoantibodies of the immunoglobulin A (IgA) and IgG classes and found a correlation between the low circulating levels of DPP IV and the high titers of anti-DPP IV autoantibodies of the IgA class. Since streptokinase (SK) is a potent immunogen and binds to DPP IV, we speculated that patients with autoimmune diseases showed higher DPP IV autoantibody levels than healthy controls as a consequence of an abnormal immune stimulation triggered by SK released during streptococcal infections. We assessed this hypothesis in a group of patients suffering from acute myocardial infarction, without a chronic autoimmune disease, who received SK as part of therapeutic thrombolysis. Concomitant with the appearance of anti-SK antibodies, these patients developed anti-DPP IV autoantibodies. These autoantibodies bind to DPP IV in the region which is also recognized by SK, suggesting that an SK-induced immune response is responsible for the appearance of DPP IV autoantibodies. Furthermore, we determined a correlation between high titers of DPP IV autoantibodies and an augmented clearance of the enzyme from the circulation. Serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) increased significantly after 30 days of SK administration, while the levels of soluble IL-2 receptor remained unchanged during the same period, suggesting a correlation between the lower levels of circulating DPP IV and higher levels of TNF-alpha and IL-6 in serum in these patients.
 ...
PMID:Streptokinase promotes development of dipeptidyl peptidase IV (CD26) autoantibodies after fibrinolytic therapy in myocardial infarction patients. 1241 58

One theory for the pathophysiology of photosensitive autoimmune skin diseases is that photoinduction of tumor necrosis factor alpha (TNFalpha) secretion leads to keratinocyte apoptosis and translocation of previously sequestered cellular antigens that then activate the immune system. We previously found an association of the overproducing TNFalpha-308 A variant with adult dermatomyositis and with subacute cutaneous lupus erythematosus. Here we focused on mannose binding lectin (MBL), which is one of several proteins involved in clearance of apoptotic cells and could thereby lessen photosensitive autoimmunity. We examined three variant MBL polymorphisms associated with decreased MBL protein (Asp54, Glu57, and the LX promoter polymorphism) in adult dermatomyositis, subacute cutaneous lupus erythematosus, and discoid lupus, and controls. The variant Asp54 allele was positively associated with adult dermatomyositis in a dose-responsive fashion (p=0.0004), as was the Glu57 allele (p=0.004). None of the three variant MBL alleles considered individually was significantly associated with either subacute cutaneous lupus erythematosus or discoid lupus. In adult dermatomyositis patients homozygous for the wild-type TNFalpha-308G allele (GG), i.e., presumably without elevated TNFalpha production, 69% had at least two of the MBL polymorphisms, versus 20% of healthy GG controls (p=0.0011). Combinations of low-producing MBL variants were over-represented in adult dermatomyositis in a dose-responsive fashion (p=0.0002). In adult dermatomyositis patients with one variant TNFalpha-308 A allele (GA), 46% had at least two MBL polymorphisms, versus 7% of GA controls (p=0.0077). Thus, low-producing MBL genes are very strongly associated with adult dermatomyositis. Our model is that genetic polymorphisms leading to overproduction of apoptotic keratinocytes and then impaired clearance of these cells contribute to the pathogenesis of adult dermatomyositis, a photoinduced autoimmune skin disease.
 ...
PMID:Mannose binding lectin (MBL) polymorphisms associated with low MBL production in patients with dermatomyositis. 1248 45

Therapeutic antibodies directed against tumor necrosis factor alpha (TNF-alpha) for the treatment of rheumatoid arthritis, and against the human EGF receptor-2 (HER2) receptor for the treatment of breast cancer have provided significant clinical benefit for the patients. The success of these antibodies has also provided strong support for the possibility that increased activity of cytokines or growth factors is causally implicated in a variety of human diseases. Interferon alpha (IFN-alpha) is induced by viruses (linked by epidemiological studies to autoimmune diseases), has significant direct effects on both epithelial cells and the immune system, and then can be further induced by the autoantibodies and apoptotic cells generated by the actions of IFN-alpha. The direct and deleterious impact on target tissues, the ability to induce an autoimmune response, and the potential for a self-sustaining cycle of induction and damage suggests that IFN-alpha could be a pivotal factor in the development of autoimmune diseases. This review will evaluate the rationale for, possible approaches to, and safety concerns associated with, targeting interferon alpha (IFN-alpha) as a therapeutic strategy for the treatment of autoimmune diseases. While the approach may be applicable to several autoimmune diseases, there will be an emphasis on systemic lupus erythematosus and insulin dependent diabetes mellitus.
 ...
PMID:Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases. 1265 Dec 25

Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's disease. We report in detail an unusual adverse reaction to infliximab therapy, a drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid-dependent Crohn's colitis, successfully managed with maintenance infliximab infusions and methotrexate, developed a lupus-like syndrome eight months after her initial infusion. This was characterized by inflammatory arthritis and an urticarial and papulosquamous rash and was accompanied by high titers of antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and by reduced levels of the C4 component of complement. After discontinuance of infliximab infusions and treatment of symptoms with intermittent courses of prednisone, the patient's arthritis progressively improved, with accompanying decrements in autoantibody titers. One year later, she has minimal joint discomfort and no rash or gastrointestinal symptoms despite also discontinuing prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation.
 ...
PMID:A lupus-like syndrome associated with infliximab therapy. 1279 23

The etiology of systemic lupus erythematosus (SLE) is unknown but genetic factors seem to play a role in the disease pathogenesis. The tumor necrosis factor alpha (TNFa) gene, encoded at the TNF locus in the MHC class III region, is now known to be an important candidate gene in SLE, due to the proinflammatory activities of the TNFa. The objectives of this study were to examine the role of the TNFa polymorphism for the susceptibility of Malaysian Chinese lupus patients to SLE and to determine its association with organ involvement. The allelic frequencies of the TNFa polymorphic variant (TNF2) of seventy lupus patients were determined during follow-up at the Medical Clinic of the National University Hospital Malaysia by PCR-RFLP technique. Sixty-four females and 6 males with a mean age of 33+/-12 years were included. Clinical data were obtained from case records. Autoantibody levels were measured by ELISA. Fifty-nine ethnically-matched blood donors were used as controls. The allelic frequency of the TNF2 variant was found to be significantly increased in the patients compared to the controls (52.8% vs 33.8%). SLE patients with the polymorphic TNF2 variant were found to be at increased risk of central nervous system involvement (p = 0.004, RR = 2.59) and to have an increased frequency of anti-La antibodies (p = 0.03). In view of these findings we suggest that TNF2 variant is playing a role in conferring susceptibility to SLE and in the disease pathogenesis.
 ...
PMID:Association of the tumor necrosis factor alpha gene polymorphism with susceptibility and clinical-immunological findings of systemic lupus erythematosus. 1556 53

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides, commonly present in corn and other cereals. Exposure to FB1 causes organ-specific diseases in various species, e.g., equine leukoencephalomalacia and porcine pulmonary edema; in mice the response is hepatotoxicity. We earlier reported that ceramide synthase inhibition by FB1, the initial biochemical effect of this mycotoxin, results in modulation of cytokine network in response to accumulated free sphingoid bases. In the current study we used NZB/NZW-F1 (NZBW) mice that have modified cytokine expression and develop lupus beginning at 5 months of age. The NZBW and C57BL/6J (CBL) mice (appropriate control) were given five daily subcutaneous injections of either saline or 2.25 mg FB1/kg/day and euthanized 24 h after the last treatment. Peripheral leukocyte counts were higher after exposure to FB1 in CBL but not in NZBW. FB1 treatment caused increases of plasma alanine aminotransferase and aspartate aminotransferase activity in CBL mice indicating hepatotoxicity; no elevation of circulating liver enzymes was recorded in NZBW mice. Hepatotoxic responses were confirmed by microscopic evaluation of apoptotic cells. The FB1-induced proliferation of cells observed in CBL strain was abolished in NZBW animals. The sphinganine accumulation in liver after FB1 was equal in both strains of mice. The NZBW strain lacked the FB1-induced increases in the expression of liver tumor necrosis factor alpha, interferon gamma, receptor interacting protein (RIP), and tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL), observed in CBL. Results confirmed our hypothesis that initial altered sphingolipid metabolism caused by FB1 leads to perturbation of liver cytokine network and ultimate cellular injury; the mice deficient in cytokine signaling are refractory to FB1 hepatotoxicity.
 ...
PMID:Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine. 1615 91


<< Previous 1 2 3 4 5 6 7 Next >>