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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA-containing immune complexes (IC) are believed to have a central causal role in the glomerulonephritis of systemic lupus erythematosus. Extracellular DNA which provides the antigenic source for these ICs circulates as oligonucleosomes (ON). The in vivo glomerular uptake of radiolabeled ON in rats, as well as its binding by cultured rat mesangial cells, was examined. The data show that the binding of ON to kidney, and specifically glomeruli, was almost fourfold greater than that of purified DNA. Uptake appeared dose-dependent and saturable, while there were no differences in hepatic or splenic uptake. Most of the nucleosomal DNA recovered from glomeruli was TCA-precipitable, and on gel electrophoresis was about 100 to 300 bp, a size sufficient to allow formation of large ICs. In vitro studies demonstrated that ON are bound by cultured mesangial cells in a dose-dependent and saturable manner, with a dissociation constant of 1.25 x 10(-10) M/liter and 750 binding sites per cell. Autoradiography of cell cultures incubated with radiolabeled ON showed deposition along the plasma membrane which was inhibited by excess unlabeled ON. The data show that binding of ON to glomeruli exceeds that of purified DNA and may be mediated by histones. ON bind to mesangial cells in a receptor-mediated fashion. The data support the hypothesis of in situ formation of DNA-containing ICs and suggest a role for the mesangial cell in lupus glomerulonephritis.
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PMID:Glomerular uptake of nucleosomes: evidence for receptor-mediated mesangial cell binding. 763 55

Exposure to occupationally relevant concentrations of the environmental pollutant, trichloroethylene (TCE), in the drinking water of autoimmune-prone MRL+/+ mice has been shown to promote the generation of lupus and autoimmune hepatitis in association with the activation of Interferon-gamma (IFN-gamma)-producing CD4+ T cells. Since blocking TCE metabolism suppressed the TCE-induced alteration in immune function, the present study was initiated to determine whether the major metabolites of TCE, trichloroacetaldehyde hydrate (TCAH) and trichloroacetic acid (TCA) could also mediate these immunoregulatory affects in vivo. TCAH and TCA were administered to the drinking water of MRL+/+ mice for 4 weeks. CD4+ T cells from TCAH and TCA-treated MRL+/+ mice, unlike CD4+ T cells from control mice, demonstrated functional and phenotypic signs of activation, as evidenced by increased IFN-gamma production in association with the increased percentage of CD62L(lo) CD4+ T cells. Interestingly, it was also found that the CD4+ T cells from the TCAH and TCA-treated mice showed a decreased susceptibility to the activation-induced cell death (AICD) form of apoptosis following re-stimulation in vitro. By demonstrating that TCAH and TCA can activate CD4+ T cells and inhibit their apoptosis following in vivo exposure represents a mechanism by which environmental toxicants may induce or accelerate the development of autoimmune disease.
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PMID:Activation and attenuation of apoptosis of CD4+ T cells following in vivo exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and trichloroacetic acid. 1550 92

Activated lymphocytes proliferate, secrete cytokines, and can make antibodies. Normally activated B and T cells meet the bioenergetic demand for these processes by up-regulating aerobic glycolysis. In contrast, several lines of evidence suggest that pathogenic lymphocytes in autoimmune diseases like lupus meet ATP demands through oxidative phosphorylation. Using (13)C-glucose as a stable tracer, we found that splenocytes from mice with lupus derive the same fraction of lactate from glucose as control animals, suggesting comparable levels of glycolysis and non-oxidative ATP production. However, lupus splenocytes increase glucose oxidation by 40% over healthy control animals. The ratio between pentose phosphate cycle (PPC) activity and glycolysis is the same for each group, indicating that increased glucose oxidation is due to increased activity of the TCA cycle in lupus splenocytes. Repetitive stimulation of cultured human T cells was used to model chronic lymphocyte activation, a phenotype associated with lupus. Chronically activated T cells rely primarily on oxidative metabolism for ATP synthesis suggesting that chronic antigen stimulation may be the basis for the metabolic findings observed in lupus mice. Identification of disease-related bioenergetic phenotypes should contribute to new diagnostic and therapeutic strategies for immune diseases.
Lupus 2010 Nov
PMID:Characterization of the metabolic phenotype of chronically activated lymphocytes. 2064 50

We present a case of a 35-year-old man having a 12-month history of multiple reddish-brown papules on the chin, forehead, cheeks, and eyelids. Histopathologic findings revealed epithelioid cell granulomas with central necrosis consistent with a diagnosis of lupus miliaris disseminatus faciei. After 9 months of combined treatment with ethambutol, rifampin, and pyrazinamide, most lesions gradually resolved but remained as severe disfiguring scars. After 10 sessions of treatments with 100% trichloroacetic acid and CO2 laser, the lupus miliaris disseminatus faciei scars have been much improved and the patient has never experienced a recurrence of disease during subsequent years of follow-up.
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PMID:Scarring of lupus miliaris disseminatus faciei: treatment with a combination of trichloroacetic acid and carbon dioxide laser. 2428 57