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)

The concentration of granulocyte elastase-alpha-1-protease inhibitor (E-AT) complex in plasma is enhanced in inflammatory processes, e.g. in septicaemia and rheumatoid arthritis, being an expression of granulocyte activation during inflammatory response. In the present study we measured E-AT and fibronectin in the plasma of 46 patients with various connective-tissue diseases in relation to the course of the disease. In about 50% of the cases, E-AT was found to be elevated to 2-3 times the normal concentrations, in relation to increasing serum content of C-reactive protein. In follow-ups over 2 years, an elevation of E-AT and a decreasing fibronectin in plasma was found in patients with activated disease. Without relation to other parameters used in connective-tissue diseases, fibronectin was found to be diminished below the normal range in 7 patients with systemic lupus erythematodes and 1 patient with overlapping syndrome. Our results indicate that the concentration of E-AT and fibronectin in plasma may be helpful parameters for judging the activity of connective-tissue diseases.
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PMID:Concentration of fibronectin and granulocyte elastase in plasma of patients with systemic connective-tissue diseases. 349 2

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus (SLE) and systemic vasculitis. Although initially described to have antibacterial properties, increasing evidence suggests that neutrophil extracellular traps (NETs) have a detrimental role in both autoimmune diseases and acute lung injury. We investigated whether NETs could be detected in a murine model of pristane-induced lupus DAH and contribute to lung injury. Such NETs might constitute a therapeutic target. NETs were characterized by immunofluorescence staining of DNA, neutrophil elastase and citrullinated histones. Evaluation of lung injury was performed by haematoxylin-eosin staining and a quantification program. Clinical status of the mice was assessed by measurement of arterial oxygen saturation and survival curves after recombinant human deoxyribonuclease-1 (Rh-DNase-1) inhalations or polymorphonuclear neutrophil (PMN) depletion. Pristane was found to promote NETs formation in vitro and in vivo. Treatment of mice with Rh-DNase-1 inhalations cleared NETs and reduced lung injury. Clinical status improved significantly, with increased arterial oxygenation and survival. Following PMN depletion, NETs were absent with a subsequent reduction of lung injury and improved arterial oxygenation. These results support a pathogenic role of PMNs and NETs in lung injury during pristane-induced DAH. Targeting NETs with Rh-DNase-1 inhalations could constitute an interesting adjuvant therapy in human DAH.
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PMID:Neutrophil extracellular traps are associated with the pathogenesis of diffuse alveolar hemorrhage in murine lupus. 3093 69

Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest that neutrophil extracellular traps (NETs) and their associated death pathway, NETosis, are sources of autoantigen in SLE. However, others and we have shown that inhibition of NETs by targeting the NADPH oxidase complex and peptidylarginine deiminase 4 (PADI4) did not ameliorate disease in spontaneous murine models of SLE. Furthermore, myeloperoxidase and PADI4 deletion did not inhibit induced lupus. Since NET formation may occur independently of any one mediator, to address this controversy, we genetically deleted an additional important mediator of NETs and neutrophil effector function, neutrophil elastase (ELANE), in the MRL.Faslpr model of SLE. ELANE deficiency, and by extension ELANE-dependent NETs, had no effect on SLE nephritis, dermatitis, anti-self response, or immune composition in MRL.Faslpr mice. Taken together with prior data from our group and others, these data further challenge the paradigm that NETs and neutrophils are pathogenic in SLE.
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PMID:Murine lupus is neutrophil elastase-independent in the MRL.Faslpr model. 3224 31