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 effect of circulating lupus anticoagulant on platelet interaction with collagen and other proteins was tested, with the aim of understanding the role of membrane phospholipids in platelet function. Plasma samples from 26 systemic lupus erythematosus (SLE) patients, containing circulating lupus anticoagulant (LAC), were examined for their effect on adhesion and aggregation of normal human platelets. We find that SLE plasma, but not normal plasma, inhibits platelet adhesion to collagen in a concentration-dependent manner. At a plasma concentration of 1% the inhibition was 73 +/- 9% (mean +/- SD). In sharp contrast, there was no effect on platelet adhesion to fibronectin. Purified IgG from the same plasma samples also had an inhibitory effect. At 15 micrograms/ml (comparable in IgG concentration to 0.1% plasma) it inhibited adhesion to collagen by 33 +/- 11%. Inhibition could be abolished by preincubation of the LAC-containing plasma with cardiolipin (CL), phosphatidylinositol (PI), and, to a lesser extent, phosphatidylserine (PS) but not with phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Inhibition could also be abolished by preincubation of the LAC-containing plasma with a 10-fold excess of washed normal platelets. The effect of 1% LAC plasma on platelet aggregation was as striking, showing 79 +/- 26% inhibition of collagen-induced aggregation, and it could also be abolished by preincubation of the LAC plasma with cardiolipin. In contrast, the effect of LAC plasma on thrombin-induced aggregation was rather modest. Our results indicate that antiphospholipid antibodies interfere with platelet adhesion and stimulation by collagen in vitro and point to an important role of external plasma membrane phospholipids, particularly PI, in collagen-induced platelet activation.
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PMID:Lupus anticoagulant antibodies inhibit collagen-induced adhesion and aggregation of human platelets in vitro. 128 33

La (SS-B) protein is known as one major antigenic target for autoantibodies from patients with certain autoimmune diseases such as Sjogren's syndrome or Lupus Erythematosus. La protein belongs to the so called "extractable nuclear antigens". Here we report that La antigen is not restricted to the nucleus as one might deduce from the exclusive nuclear staining pattern of patient anti-La antibodies but after stimulation of serum-starved cells with 10% fetal calf serum (FCS) appears and stays for at least 45 min at the outer surface of CV-1 cells being available for binding of anti-La antibodies. In addition we found that a minor part of La antigen associates with the extracellular fibronectin network. After addition of 10% FCS to serum starved cells this extracellular autoantigen disassembled from the extracellular matrix and was taken up again by the cells. Incubation of serum starved cells with mercuric chloride, a known potent inducer of autoantibodies, also resulted in a detachment of the extracellular matrix associated La protein. From our studies it becomes likely that La protein itself is the antigen during autoimmunization. Moreover, once developed, anti-La antibodies might be able to bind to cell surface expressed La protein resulting in a damage of these cells leading to the inflammational events known to occur during disease.
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PMID:Translocation of the nuclear autoantigen La to cell surface: assembly and disassembly with the extracellular matrix. 171 61

Electron microscopy has revealed that the deposition of immunoglobulin in the skin of lupus erythematosus (LE) patients occurs on and below the basal lamina of the basement membrane (BM). The composition of the BM is now to some extent known, and antibodies have been developed against several of its individual components. In this study, we attempt to elucidate the status of some matrix molecules in the dermoepidermal junction in LE. Lesional and nonlesional skin from LE patients was examined using immunofluorescence microscopy with monoclonal and polyclonal antibodies against 6 matrix molecules. Immuno-electron microscopy using monoclonal antibodies was used to discern changes in type IV and type VII collagen. By immuno-fluorescence microscopy, type IV collagen, type VII collagen, and fibronectin were altered in lesional skin. There was a statistically significant correlation between the presence of immunoglobulin and alteration of type IV collagen and type VII collagen in lesional skin. The alterations in type IV and type VII collagens were confirmed on immuno-electron microscopy which showed fragmentation of staining of both antigenic components, particularly type IV collagen.
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PMID:Characterization of the changes in matrix molecules at the dermoepidermal junction in lupus erythematosus. 177 51

In patients with systemic lupus erythematosus (SLE) both a haemorrhagic diathesis and a tendency to thrombosis of the venous and arterial vessels can be observed. In the course of the disease, thrombosis of the leg or pelvic veins developed in 20 per cent of 188 patients. The levels of alpha 2-plasmin inhibitor, plasminogen, fibronectin and of factor VIII complex were increased in patients with SLE compared with a control group. Fifty per cent of the patients showed no increase in fibrinolytic activity after venous occlusion measured with the fibrin plate method. This suggests a reduced fibrinolytic capacity in SLE probably caused by alteration of the endothelial cells through immune complex vasculitis. In addition, the lupus anticoagulant and an acquired antithrombin III deficiency in nephrotic syndrome in SLE are to be considered thrombophilic mechanisms. In the individual case there is an overlapping of hyper- and hypocoagulability.
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PMID:[Status of fibrinolysis in systemic lupus erythematosus]. 242

The intraglomerular location of coagulation-fibrinolysis factors (CFF) and a platelet membrane antigen (glycoprotein IIb-IIIa; GPIIb-IIIa) was determined in 101 patients with various glomerular diseases. Renal biopsy specimens were examined by immunofluorescence microscopy, using antisera against fibrinogen/fibrin reactive antigen (FRA), cross-linked fibrin degradation products (XL-FDP), fibronectin (FN), factor XIII-subunit a (F-XIIIa), plasminogen (Plg), alpha 2-plasmin inhibitor (alpha 2-PI) and GPIIb-IIIa. Intraglomerular deposits of the CFF were found at high rates in patients with IgA glomerulonephritis (GN), membranous nephropathy (MN) and lupus GN. The coexistence of deposits of these factors was ascertained by the double-staining method. The deposition rates of XL-FDP and GPIIb-IIIa were very low in patients with minimal-change nephrotic syndrome and focal glomerulosclerosis. Some cases of diabetic glomerulosclerosis (DGS) showed CFF deposition. FRA deposits associated with F-XIIIa and FN may indicate the presence of the cross-linked fibrin. Furthermore, the presence of Plg deposits together with alpha 2-PI and XL-FDP suggests the deposition of fibrin followed by fibrinolysis, but not of fibrinogen, and the coexistence of GPIIb-IIIa suggests the involvement of platelets in the reactions. These studies provide evidence that stabilized fibrin deposition with subsequent fibrinolysis and platelet activation take place in glomeruli in a fairly large proportion of patients with IgA GN, MN and lupus GN and in some cases of DGS.
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PMID:Intraglomerular deposition of coagulation-fibrinolysis factors and a platelet membrane antigen in various glomerular diseases. 256 3

The acute-phase proteins, fibronectin (Fn) and serum amyloid P (SAP), are opsonins which by virtue of their adhesive properties may be involved in the glomerular nephritis associated with splenic lupus erythematosus (SLE). Because of their possible involvement in the pathophysiology of lupus, plasma Fn and SAP levels from three strains of autoimmune mice were measured over time to determine if Fn and SAP rose as the mice sickened and renal function degenerated. Baseline levels of Fn and SAP were measured when the mice were between 1.5 and 3 months of age. The characteristic rapid onset of autoimmune disease in MRL/1pr mice was accompanied by a two- to threefold increase in plasma Fn and SAP by Day 100. The B/W mice, which develop autoimmune disease more slowly, did not have a significant increase in plasma Fn and SAP until Day 240. The NZB mice, with the most delayed onset of disease, exhibited a modest but significant elevation of plasma Fn and SAP by Day 360. Histologic examination of the kidneys of B/W and NZB mice indicated that pathological abnormality of the glomeruli and tubules coincided with the elevation of plasma Fn and SAP levels. In contrast, blood samples taken over time from normal BALB/c mice did not possess abnormal levels of Fn or SAP. It appears that elevation of plasma Fn and SAP in the MRL/1 pr, B/W, and NZB mice is related to the onset and severity of autoimmune disease and the subsequent loss of renal function.
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PMID:Elevation of plasma fibronectin and serum amyloid P in autoimmune NZB, B/W, and MRL/1pr mice. 319 16

Fibronectin (Fn) is an integral constituent of the endothelial cell surface and the basement membrane. The mechanism for binding DNA/anti-DNA complexes to Fn was examined in a solid-phase assay. In physiological buffer, a low-affinity binding of DNA was observed with Fn and optimal binding was seen at pH 6.5 and in the absence of Ca2+. Further, the interaction of DNA to Fn was inhibited when DNA was complexed to anti-DNA antibody. However, complement Clq mediated the binding of complexes to Fn at pH 7.4 and it was proportional to the extent of the dissociation of Cl. Cl inactivator (Cl-In) appeared to play a modulating role; whereas at low concentrations (Cl:Cl-In::4: less than 1) it enhanced the binding of complexes to Fn, higher concentrations inhibited the binding. Further, sera from patients with active systemic lupus erythematosus reacted with Fn, which was shown to be dependent on the presence of Clq and was minimally affected by DNase treatment of sera, indicating a relatively minor role of DNA in the direct binding of DNA to Fn. These findings support "circulating immune complex" hypothesis in the pathogenesis of lupus glomerular immune complex deposition disease.
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PMID:Interaction of fibronectin with DNA/anti-DNA complexes from systemic lupus erythematosus: role of activated complement Cl in modulation of the interactions. 325 31

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

Fibrinolytic and other factors have been measured in 73 patients with systemic lupus erythematosus or related conditions to determine whether clinical thrombosis, a common feature of these disorders, is associated with defective fibrinolysis. Twenty five of 72 (35%) patients, compared with two of 22 (9%) controls, showed a low level of plasminogen activator activity in response to venous occlusion, suggesting decreased fibrinolytic potential. In addition, mean plasma levels of von Willebrand factor antigen and fibronectin were markedly raised in the patients (mean (SD) 384.5 (277)% and 727 (436) mg/l respectively) compared with healthy controls (100 (50)% and 306 (65) mg/l). These data suggest a degree of endothelial cell dysfunction. No clear correlation was found between a history of thrombosis and any plasma factor measured, except for prolongation of clotting tests suggestive of the 'lupus anticoagulant'.
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PMID:Indications of vascular endothelial cell dysfunction in systemic lupus erythematosus. 350 Jun 77

The fibronectins are a group of glycoproteins present in plasma and cellular tissues. They are produced by fibroblasts and endothelial cells, and are of importance in cellular adhesion and spreading. Fibronectin has a special affinity to fibrous proteins such as collagen and elastin, and is abundantly present in normal skin in the dermo-epidermal junction area, dermis, and subcutis. Fibronectin is not found in the epidermis. In a number of diseases fibronectin can be demonstrated in the epidermis of lesional skin, with or without affection of the dermo-epidermal junction area. Such changes are found in psoriasis vulgaris, lupus erythematosus, bullous pemphigoid and dermatitis herpetiformis, and represent the exoserosis of plasma and/or transepidermal elimination of degenerated tissue structure with fibronectin from the dermo-epidermal junction and the papillary dermis.
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PMID:Studies on fibronectin in the skin: VI. Intra-epidermal depositions in vulgar psoriasis, lupus erythematosus, bullous pemphigoid and dermatitis herpetiformis. 616 9


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