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)

Fifty sera containing antinucleolar antibodies were o gathered in a routine laboratory during testing for antinuclear antibodies with indirect immun-fluorescence over a five-year period. The patients involved were suffering from sclerodermia (13 cases), rheumatoid arthritis (7 cases), polymyositis (3 cases), lupus (2 cases), various rhumatismal disease (59 cases) and non rhumatismal diseases in 16 cases, including 5 malignant diseases. In 80 per cent of the cases nucleolar fluorescence was combined with nuclear fluorescence of another type. The antibodies were almost always of the IgG category and belonged in 2/3 of cases to several immunoglobulin categories, most often IgG-IgA. Pretreatment of the liver cuttings with RNase always modifies the nucleolar fluorescence, most often making it negative, and pretreatment with DNase using a combination of enzymes 10 times higher also modifies it (more often decreasing it than making it negative), which indicates that the nucleolar antigen, probably an ARN with a low molecular weight, also depends upon the ADN.
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PMID:[Antinuclear antibodies: immunological characteristics and clinical significance]. 31 10

Clinical and laboratory findings were correlated from 46 patients with IgG localization in epidermal nuclei in a speckled (particulate) pattern on direct immunofluorescence of normal skin. Cutaneous manifestations included lupus erythematosus (LE), swollen hands or sclerodactyly, alopecia, vasculitis, and dyspigmentation. Systemic manifestations included arthritis or arthralgia, Raynaud's phenomenon, serositis, vascular headaches, mild renal disease, myositis, and sicca syndrome. High titer (mean = 1:142, 800) serum antibody to extractable nuclear antigen (ENA) was found in 81%. Eighty-six percent had antibody to an RNase-sensitive antigenic component of ENA (ribonucleoprotein or RNP); 14% had antibody to an RNase-resistant ENA termed Sm. Deposition of IgG in a speckled pattern in epidermal nuclei is an immunopathologic marker for a subset of connective tissue disease characterized by antibody to ENA. Those with Sm specificity had systemic LE (SLE); Those with RNP specificity had Raynaud's phenomenon usually associated with overlapping features of SLE, scleroderma, and/or dermatomyositis.
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PMID:Speckled (particulate) epidermal nuclear IgG deposition in normal skin. Correlation of clinical features and laboratory findings in 46 patients with a subset of connective tissue disease characterized by antibody to extractable nuclear antigen. 34 15

1. We describe new autoantibodies which recognize two cytoplasmic proteins of 30 and 26 kDa. They were detected by Western blot analysis in the sera of 6 of 79 randomly selected systemic lupus erythematosus (SLE) patients and are denoted anti-JA antibodies. This antibody specificity is different from the previously described lupus autoantibodies, anti-P and anti-S10. 2. The targeted autoantigens are trypsin sensitive, and resistant to RNase and DNase treatment. The binding to the antigens was not modified when reticulocyte ribosomes were prepared with protease inhibitors indicating that these are primary antigens and not degradation products. Several lines of evidence suggest that these proteins are almost certainly part of the ribosome. 3. Anti-JA reactivity was not observed in the sera from 60 patients with other autoimmune diseases or from normal individuals. In contrast, 55% of lupus sera selected for a high titer of anti-dsDNA (double stranded DNA) and LE cells were also anti-JA positive. 4. Anti-JA antibodies may be useful as a specific serological marker for disease activity in SLE. The strong association with anti-dsDNA antibodies and LE cell in the sera of SLE patients requires further study.
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PMID:Antibodies to new cytoplasmic autoantigens: anti-JA, a potential marker for disease activity in systemic lupus erythematosus. 134 36

This study presents 8 dogs of German Shepherd breed (6 males, 2 females, 2-5 years of age at onset of the disease) with a lupus like syndrome characterized by febrile polyarthritis, wasting, nephropathy, cutaneous lesions and high positive titres of ANA (antinuclear antibodies) of speckled type. The serum autoantibodies were further characterized by double immunodiffusion against ENA (extractable nuclear antigen), ELISA for Histone antibodies (Histon fraction H-24A and H-3S), indirect IF on rat-liver sections, non treated and RNase/DNase digested sections for DNP/RNP antibodies, and smears of a hemoflagellate C. luciliae for antibodies vs doubbel strained DNA, (dsDNA). Thus, the high ANA titres in these dogs represent varying types of autoantibodies against nucleoproteins of both DNA and RNA nature, associated histone antigens and non-histone antibodies (RNA and Sm) as well. Rheumatoid Factor titres in serum from these dogs were low or negative. Immunoglobulin deposits at dermo-epidermal junctions were demonstrated in some of the dogs with hyperkeratotic skin lesions. High concentration of serum-IgG was a constant finding in combination with anemia and in most cases leukopenia probably related to the chronic inflammatory process in these animals. Autoimmune hemolytic anemia (AIHA) or thrombocytopenia was not detected in these dogs.
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PMID:Serum auto antibodies and clinical/pathological features in German shepherd dogs with a lupuslike syndrome. 195 Aug 49

A case of isoniazid (INH)-induced lupus occurring in a 62-year-old man is presented. He visited our hospital in May 1986 and a cavitary lesion was found in the right upper lobe on a chest roentgenogram. He had no previous history of treatment with antituberculotic agents. Though acid-fast bacilli were not found in his sputum, pulmonary tuberculosis was strongly suspected and INH, rifampicin and ethanbutol were administered. Four days after starting the treatment, minimal left pleural effusion was seen on chest X-ray film. Three months later he began to complain polyarthralgia in his digital joints. In a pleural effusion many lymphocytes were found; and the antinuclear antibody (ANA), the anti-extractable nuclear antigens (ENA) antibody, and the RNase resistant anti-ENA antibody were positive, and their titres were 20x, 1000x and 1000x, respectively, and the immune complex (IC) was 16.0 micrograms/ml (LT5). In blood serum, the ANA test the anti-ENA antibody and the RNase resistant anti-ENA antibody were positive with titres 40x, 640x and 640x respectively; and the IC was 14.0 micrograms/ml, and the RA test was positive. The improvement of clinical findings and disappearance of auto-antibodies seen after stopping INH confirmed the diagnosis as INH-induced lupus.
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PMID:[A cases of isoniazid-induced lupus]. 281 Sep 99

This report describes the behavior of antigenic small nuclear ribonucleoproteins (snRNPs) in native isofocusing gels. These RNA-protein complexes exhibited true isofocusing characteristics only when in the complexed form. Deproteinized snRNAs migrated to pH ranges which varied according to the pH of the application site. Immunological assays using lupus sera which recognized the La, Sm, and RNP determinants on these snRNPs established that the La and the Sm/RNP antigens segregated to pH 4.7-4.9 and 5.5-7.5, respectively. RNase digestion of these snRNPs did not alter the isofocusing migration of either the Sm or the La determinants. These antigenically active fractions contained the appropriate protein and RNA species shown by immunoprecipitation studies to associate with these antigenic determinants. The isofocusing fractions containing the uridylic acid-snRNPs were fully immunoprecipitable by anti-Sm sera, confirming their particulate integrity after isofocusing.
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PMID:Isofocusing of antigenic small nuclear ribonucleoproteins. I. Compositional analysis. 316 13

Three major components of the plasminogen activators (PA)/plasmin system are synthesized physiologically in glomeruli, and can be involved in glomerular proteolysis and extracellular matrix metabolism: tissue-type PA (tPA), urokinase (uPA) and PA inhibitor type 1 (PAI-1). To explore the possible role of a dysregulation of the plasmin protease system in the development and progression of lupus-like glomerulonephritis, we studied the expression of the renal plasmin protease components during the course of the disease, either acute, induced by IgG3 monoclonal cryoglobulins, or chronic, occurring spontaneously in three different lupus-prone mice: (NZBxNZW)F1, BXSB and MRL-lpr/lpr. RNase protection assays and in situ hybridizations revealed a marked glomerular induction of PAI-1 mRNA abundance without any significant changes in renal tPA and uPA mRNA levels in the two different types of lupus-like glomerulonephritis. The overexpression of PAI-1 mRNA occurred in parallel with a significant decrease in glomerular tPA-catalyzed enzymatic activity as determined by zymographic analysis. In addition, a concomitant increase in glomerular expression of transforming growth factor beta 1 (TGF-beta 1) mRNA was observed. The demonstration of a close correlation between the PAI-1 and TGF-beta 1 mRNA levels and the severity of lupus-like glomerular lesions suggests that a pertubation of the glomerular PA/PAI balance, resulting from a marked TGF-beta 1-mediated induction of PAI-1 gene expression, plays an important role in the progression of lupus-like glomerular lesions, leading to glomerulosclerosis.
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PMID:Induction of plasminogen activator inhibitor type 1 in murine lupus-like glomerulonephritis. 854 2

The murine MRL/lpr model of lupus nephritis is characterized by a systemic autoimmune syndrome closely resembling the human disease. The lpr mutation represents a defect in the expression of the apoptosis-signaling Fas antigen gene which causes accelerated autoimmune disease in MRL/ lpr mice and a milder, non-lethal autoimmune syndrome in C57BL6-lpr/lpr mice. The role of cytokines in autoimmune pathogenesis and its relationship with the lpr mutation remains poorly understood. In this study we utilized a RNase protection assay to quantitatively and simultaneously examine the expression of 10 different cytokine genes, namely IL-1 alpha, II-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, and TNF-beta in kidney, spleen, liver, and lymph nodes obtained from pre-diseased and diseased lupus-prone MRL/lpr, pre-diseased MRL/+2 and C57BL/6-lpr mice, as well as healthy non-autoimmune C57BL/6 and Balb/c mice. Diseased MRL/lpr mice demonstrated marked and predominant IL-1 beta gene upregulation in kidneys, liver, lymph nodes and spleen. Increased message for both TNF-alpha and IFN-gamma genes was also observed in lymph nodes, and less consistently, in the spleen, and kidneys derived from diseased MRL/lpr mice as compared to pre-diseased MRL/+2 or normal nonautoimmune control mice. Furthermore, a modest increase in the expression of both IL-1 beta and IFN-gamma message was observed in lymphoid organs of pre-diseased MRL/lpr and C57BL/6-lpr mice compared with MRL/+2 and C57BL/6 controls, respectively. Increased IL-1 beta gene expression was associated with the presence of the lpr mutation, was observed during the prediseased stage, and increased during active disease in both male and female mice. In summary, these results demonstrate that generalized up-regulation of IL-1 beta gene expression, in concert with a more limited up-regulation of both TNF-alpha and IFN-gamma expression, are prominent features of the autoimmune syndrome in the MRL/lpr model of SLE and may contribute to the disease-accelerating effect of the lpr mutation.
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PMID:Cytokine gene expression in the MRL/lpr model of lupus nephritis. 880 76

Protease nexin 1 (PN-1), a potent serpin-class antiprotease, is thought to be synthesized in the murine kidney. However, neither the cellular localization of PN-1 synthesis nor its role has yet been defined. To address these questions, we determined by in situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accumulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions. In normal kidneys, PN-1 mRNA was detected primarily in glomeruli, most likely in mesangial cells. The glomerular expression of PN-1 was substantially enhanced not only in lupus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid factors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies. In contrast, no modulation of PN-1 mRNA levels was observed during the course of lipopolysaccharide-induced acute tubular necrosis. A constitutive PN-1 gene expression and its up-regulation during glomerular injury suggest a possible role for PN-1 in glomerular biology. In view of its high inhibitory activity towards thrombin, mesangial PN-1 may be involved in the control of glomerular coagulation following initial glomerular injuries.
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PMID:Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies. 894 77

A general characteristic of lupus-prone mice (and humans) is the expedited accumulation of large numbers of presumably self-reactive activated/memory phenotype T cells. The mechanism by which these cells escape apoptosis has not been defined. We used activated/memory phenotype CD4+ cells from male BXSB mice with early-life severe lupus-like disease to investigate cell cycle status and apoptosis susceptibility, and to determine the role of corresponding genes in survival of these cells. In vitro acridine orange staining indicated that most of the rapidly accumulating memory phenotype CD4+ T cells of 4-month-old male BXSB mice are G1 arrested. Long-term bromodeoxyuridine in vivo labeling also showed that with advanced age, there was a shift of the CD4+ CD44(hi) male cells from predominantly cycling to predominantly noncycling. Moreover, the CD4+ CD44(hi) cells of older males were refractory to anti-CD3-induced proliferation and apoptosis. Using a multiprobe RNase protection assay encompassing riboprobe panels for cell cycle and apoptosis-related genes, we found that these cells exhibited high expression of certain members of the Ink4 (p18Ink4C) and Cip/Kip (p21Cip1) families of cyclin kinase inhibitors as well as of the apoptosis-inhibiting Bcl-xL gene. Western blot analysis confirmed increased levels of Bcl-xL and p21Cip1, and also identified increases in another cyclin kinase inhibitor, p27Kip1. We propose that in autoimmunity, self-reactive CD4+ cells are subjected to successive rounds of activation/division that eventually lead to a build-up in cyclin-dependent kinase inhibitors. Once high levels of such inhibitors are reached, they cause refractoriness to further activation, impaired cell cycle entry and resistance to apoptosis, a situation akin to replicative senescence.
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PMID:G1 arrest and high expression of cyclin kinase and apoptosis inhibitors in accumulated activated/memory phenotype CD4+ cells of older lupus mice. 929 25


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