Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoantibodies to ribosomal P-proteins are present in 12-16% of patients with systemic lupus erythematosus and are associated with neuropsychiatric disease. As the ribosomal P proteins are located in the cytoplasm, the pathogenic effects of their cognate autoantibodies are unclear. In this study affinity-purified anti-P autoantibodies were used to explore the cell surface of several types of human and animal cells. Immunofluorescence as well as EM immunogold analysis demonstrated, on the surface of human hepatoma cells, the presence of an epitope that is antigenically related to the immunodominant carboxy terminus of P-proteins. The presence of this epitope was also demonstrated on the surface of human neuroblastoma cells and, to a lesser extent, on human fibroblasts. Furthermore, the Western blot technique revealed in purified human and animal plasma membranes a 38-kD protein that is closely related or identical with ribosomal P0 protein. The availability of reactive P peptide on the surface of cells makes possible the direct effect of autoantibodies on the function and viability of cells that express this antigenic target. This delineates one of the possible impacts of anti-P antibodies in disease expression.
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PMID:Autoantibodies to the ribosomal P proteins react with a plasma membrane-related target on human cells. 131 50

An antibody was detected in the sera from patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement that reacted with a 50-kD antigen in the plasma membrane of brain synaptic terminals. The 50-kD antigen was solubilized with Triton X-100 from preparations enriched with synaptic plasma membranes, and was partially purified by molecular sieve filtration column chromatography. The sera of 19 of 20 CNS-SLE patients showed strong to moderate immunoreactivity with the 50-kD protein in Western blots. Immunoreactivity with the 50-kD protein was also detected in the cerebrospinal fluid of CNS-SLE patients. Control sera from healthy individuals did not react with the 50-kD protein. Low to background reactivity was detected in 35% of a group of SLE patients without CNS manifestations, and in 3% of patients displaying other connective tissue diseases. A total of 100 individuals were tested in this study. Purified autoantibodies to the 50-kD protein from CNS-SLE patients were used for immunofluorescent labeling of neuroblastoma cells. The immunofluorescent staining revealed a distinct macular distribution pattern on the surface of the cell membrane. Taken together, the data suggest that the 50-kD protein may be an important target for autoantibodies, preponderantly found in CNS-SLE patients, and that the antigen may play a role in the pathogenesis of some neurological manifestations in SLE.
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PMID:Systemic lupus erythematosus patients with central nervous system involvement show autoantibodies to a 50-kD neuronal membrane protein. 150 Aug 60

We have tested 36 patients with the Lambert-Eaton myasthenic syndrome for serum antibodies to voltage-gated calcium channels by using an immunoprecipitation assay with [125I] omega-conotoxin-labeled voltage-gated calcium channels extracted from a human neuroblastoma cell line, SKN-SH. Forty-four percent of these patients had significant levels of antibody (30-1,466 pM) compared with healthy control individuals (less than 15 pM). The incidence of positive sera in patients without associated small cell lung carcinoma (61%) was greater than in those patients with small cell lung carcinoma (28%). Results correlated strongly with results obtained using voltage-gated calcium channels extracted from the small cell lung carcinoma line, MAR5. Anti-voltage-gated calcium channel antibody titers did not correlate with disease severity across individuals, but longitudinal studies in 2 patients receiving immunosuppressive therapy showed a clear inverse relation between antibody titer and an electromyographic index of disease severity. The incidence of positive sera among patients with other neurological disorders was not significant, but 8 of 12 patients with rheumatoid arthritis or systemic lupus erythematosus had raised titers (30-82 pM). We conclude that the antibodies detected in this assay are heterogeneous and that some of them are likely to be implicated in this disorder of neuromuscular transmission. The assay should prove useful as an additional diagnostic aid in patients with Lambert-Eaton myasthenic syndrome.
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PMID:Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. 164 44

The nonobese diabetic (NOD) mouse, in which major histocompatibility complex genes may be involved in the susceptibility to diabetes, has been developed as a model of autoimmune diabetes. The NOD mouse expresses I-A-encoded class II major histocompatibility complex antigens, which differ from those of other mouse haplotypes by the presence of a serine at position 57 of the A beta chain. Identifying islet autoantigens may help elucidate the role of class II antigens in the activation of autoreactive T cells and, thus, in the development of diabetes. We have detected autoantibodies directed against a 58-kDa islet cell antigen in NOD mice but not in other strains, including lupus-prone mice. Apart from insulin-secreting cells, the 58-kDa antigen was only found to be expressed by neuroblastoma cells and was identified as peripherin, an intermediate filament protein previously characterized in well-defined neuronal populations. This autoantigen cross-reacted with I-Anod class II antigens, suggesting that it may contribute to defective self-tolerance of islet beta cells in the NOD mouse.
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PMID:Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products. 172 86

Using human neuroblastoma cell lines (IMR-6, NMB-7, SK-N-Mc, SK-N-SH) as sources, we characterized surface neuronal antigens as an initial step in determining the pathogenic role and clinical significance of neuronal antibodies in systemic lupus erythematosus (SLE) patients. SLE sera were screened for the presence of surface neuronal antibodies using a mixed hemadsorption assay. Thirty SLE sera were further tested by Western blotting and immunoprecipitation of lysed IMR-6 cells. Western blotting revealed binding to predominantly intracellular antigens, none of which was restricted to neuroblastoma cells. In contrast, immunoprecipitation experiments demonstrated binding to a 97K antigen, which appeared to be of surface origin, by 3 SLE sera. This was not present on non-neuronal cells and was not precipitated by sera from healthy or disease controls. This 97K antigen was also precipitated from the neuroblastoma cell line NMB-7, but was not present on SK-N-Mc or SK-N-SH cells. Precipitation was depleted by preabsorption with viable IMR-6 and NMB-7 cells, but not with non-neuronal cells. Thus, some SLE sera recognize a 97K neuronal antigen on select neuroblastoma cells.
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PMID:A novel neuronal antigen identified by sera from patients with systemic lupus erythematosus. 246 13

Neuroblastoma cell lines have been extensively used to identify the presence of brain reactive autoantibodies in the sera of patients with systemic lupus erythematosus (SLE) who have neuropsychiatric involvement and in the animal models (murine) of this disorder. In this study, a characterization of murine neuroblastoma cell surface antigens, from the adrenergic A2(1) cell line, have indicated both similarities and differences with the cell surface antigens of normal mouse brain. It has also shown that some of these antigens are nervous system specific, whereas others are not. These data indicate that a more precise definition of the antigens on the surface of neuroblastoma cells, with which anti-brain autoantibodies react, is necessary for an understanding of the neuropsychiatric manifestations associated with autoimmune diseases such as SLE.
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PMID:Characterization of cell surface antigens on the adrenergic neuroblastoma clone A2(1). 340 42

A human neuroblastoma cell line, LA-N-1 was used as a target cell in a I131 radiolabeled staphylococcal protein-A (I131-SpA) binding assay, to characterize the pattern of antineuronal activity of human sera in fifty-four cases of systemic lupus erythematosus (SLE) including twenty-six patients with neuropsychiatric manifestations of SLE (LE-CNS), out of which ten were pediatric patients aged eleven to eighteen years, thirty-six normal donors and sixteen rheumatoid arthritis patients. The IgG binding activity of normal control sera with LA-N-1 neuroblastoma cells was determined to be 998 +/- 490 cpm I131-SpA, per 5 micrograms LA-N-1 protein (mean +/- SD), 2936 +/- 2607 cpm I131-SpA per 5 micrograms LA-N-1 protein for rheumatoid arthritis patients, 5109 +/- 3304 cpm I131-SpA per 5 micrograms LA-N-1 protein for SLE patients. The binding activity of for LE-CNS patients sera was: 10 565 +/- 2993 and 15 346 +/- 2993 cpm I131-SpA per 5 micrograms LA-N-1 protein, for the pediatric and adult group of patients respectively. Absorption assays disclosed that the antineuronal IgG autoantibody detected in the LE-CNS group of patients is cross reacting with human adult brain, while the anti-neuronal activity of rheumatoid arthritis and SLE patients could be removed by sequential absorption with homogenates of human lung, liver, and kidney, fetal calf serum, human muscle and human lymphocytes. We conclude that detection of autoantibodies binding to LA-N-1 human neuroblastoma cells may be helpful in the diagnostic workup of pediatric and adult LE-CNS patients.
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PMID:Autoantibodies to neuroblastoma cell surface antigens in neuropsychiatric lupus. 396 Feb 80

The diagnosis of neuropsychiatric systemic lupus erythematosus (NP-SLE) is clinical and one of exclusion. Brain cross-reactive lymphocytotoxins or neuronal antibodies have been proposed as a mechanism underlying NP-SLE. We assessed the clinical relevance of neuronal cell binding antibodies using a standardized clinical definition of NP-SLE. Serum from 54 SLE patients and 77 controls were tested for binding to 3 neuroblastoma and 3 glioblastoma cell lines. Thirty-three SLE patients (61%) fulfilled clinical criteria for the diagnosis of NP-SLE; of these, 55% had serum binding activity to both neuroblastoma and glioblastoma cell lines, compared with 33% of the other SLE patients. When reactivity to neuroblastoma cell lines only was assessed, 43% of NP-SLE patient sera demonstrated binding activity, versus 14% of sera from the remaining SLE patients. Control subjects' reactivity to neuroblastoma cell lines was positive in 12% of sera. Analysis of serum reactivity using non-neuronal cell lines revealed that neuroblastoma, but not glioblastoma, cell binding was specific. NP-SLE patients with evidence of diffuse symptomatology had a higher mean titer of neuroblastoma cell line binding than those with focal symptomatology. Using a panel of substrates, one can identify a significant proportion of patients who are independently defined as having NP-SLE, who demonstrate specific serum neuronal antibodies.
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PMID:Antineuronal antibodies in neuropsychiatric systemic lupus erythematosus. 401 26

Sera from a patient with systemic lupus erythematosus (SLE), tested by indirect immunofluorescence on frozen tissue sections, gave granular cytoplasmic staining of hepatocytes, gastric chief cells, exocrine cells of the pancreas and submandibular glands, and cerebellar Purkinje cells. In acetone-fixed monolayers of rat embryonic fibroblasts, 3T3 cells, mouse neuroblastoma cells, and cells from a human melanoma and colon carcinoma cell line, the sera stained perinuclear cytoplasmic granules which radiated out towards the cell periphery. More mature and differentiated fibroblasts from rat of human foetal lung showed staining of reticular cytoplasmic structures corresponding to phase-dense rough endoplasmic reticulum (RER). Nucleoli were prominently stained in all cultured cells. Serum absorption with ribosomes inhibited all antibody activity but absorption with RNA or with RNase-treated ribosomes resulted only in partial inhibition. Monolayers of RNase-treated fibroblasts gave weaker staining reactions compared to control untreated cultures. These observations suggest that the autoantibody is directed against ribosomal RNA and ribosomal protein present in cytoplasmic polyribosomes, in RER and in nucleoli.
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PMID:Autoantibody to ribosomes and systemic lupus erythematosus. 700 92

A non-Fc receptor-bearing mouse neuroblastoma cell line, Neuro-2a, was used in indirect immunofluorescence tests to characterize the pattern of anti-neuronal activity of human sera in 41 cases of systemic lupus erythematosus (SLE), including seven cases of cerebral lupus, 30 "disease controls" (rheumatoid arthritis and chronic active hepatitis) and 30 healthy subjects. The immunofluorescence reaction with Neuro-2a gave a uniform ring fluorescence of the cell surface of cultured cells at 4 and at 37 degrees C, clusters were seen at 5 to 10 min and surface globules at 20 to 120 min. Titres of antibody to Neuro-2a in SLE ranged from less than 5 (seven cases), 5 to 20 (23 cases) and greater than or equal to 40 (11 cases). Titres of 80 to 160 were given by five of seven cases of cerebral lupus and two of 34 cases without cerebral lupus. Antibody to Neuro-2a was demonstrable in subjects without SLE, but to lower titres (less than 5-20). Of 11 SLE sera with antibody titres greater than or equal to 1:40, the antibody class was IgM in eight, IgG in two and both IgM and IgG in one. Absorption studies indicated that serum reactivity against Neuro-2a cells could be removed from some SLE sera with the cultured human neuroblastoma cell line, SK-N-SH, but not with mouse fibroblasts, mouse 3T3 cells, rat C6 glioma cells, rat transformed mesenchymal cells, nor by homogenates of mouse brain, heart, liver of kidney. Detection of antibody to Neuro-2a cell may be helpful in identifying patients with cerebral disease due to SLE.
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PMID:Autoantibody to a novel neuronal antigen in systemic lupus erythematosus and in normal human sera. 703 32


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