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)

Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.
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PMID:Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus. 814 10

Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.
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PMID:Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specific Psathyrella velutina lectin. 833 95

Nervous system involvement in systemic lupus erythematosus (SLE) has been linked to the production of autoantibodies that may bind to surface antigens on neuronal cells and cause cellular dysfunction. At present, little is known of the target antigens recognized by these antibodies. The aim of the present study was to examine reactivity to rat brain synaptosomes (RBS) in sera from patients with SLE. Sera from 73 unselected SLE patients and controls were studied. Crude RBS were prepared by differential centrifugation and enriched fractions of synaptosomes (SY-E), myelin (MY-E) and mitochondria (MI-E) were obtained by sucrose density centrifugation. Rat liver (RL) was used for control antigens. Wheat-germ lectin affinity chromatography yielded membrane-enriched fractions of RBS, RL and whole rat brain (WRB). Antibody binding was examined by Western blotting. IgM reactivity was detected in 12/73 sera (16%) and was directed to proteins of 62K, 48K 37K molecular weight. IgG reactivity was present in 5/73 sera (7%) to proteins of 52K, 48K, 37K and 29K molecular weight. Except for binding to the 52K and 37K proteins these autoantibodies were not detected in control sera. Reactivity was usually absent, or present in reduced amounts, in WRB and RL. Additional experiments revealed that binding of IgM to 62K was found predominantly in SY-E and MY-E fractions, 48K in SY-E and MI-E fractions and 37K in the SY-E fraction. Binding of IgG to 48K and 29K was detected in the SY-E and MI-E, but reactivity to 52K and 37K was restricted to the SY-E fraction. Thus, sera from SLE patients contain antibodies to synaptosomal antigens that may contribute to the neuropsychiatric manifestations of the disease.
Lupus 1993 Feb
PMID:Brain synaptosomal antibodies in systemic lupus erythematosus. 848 58

Wheat germ lectin affinity chromatography and temperature-induced phase separation with Triton X-114 were evaluated for the isolation of surface neuronal antigens from rat and human brain and from human neuroblastoma cell lines IMR-6 and SK-N-SH. Both techniques yielded surface proteins which were free of contamination by intracellular proteins but temperature-induced phase separation was technically less demanding and less expensive, required a shorter assay time and resulted in a superior quantity and quality of isolated proteins. Rat brain surface proteins were used for characterization of antineuronal antibody reactivity in sera from patients with systemic lupus erythematosus (SLE). Western blotting identified reactivity in 15 of 75 (20%) SLE sera compared to five of 95 (5%) normal controls (P 0.006). In rat brain the molecular weight of the individual proteins identified ranged from 59 kDa to 22 kDa. Six of these were also present in human brain and two were present in neuroblastoma cell lines. Absorption studies indicated that some of the antigenic proteins were either restricted to brain tissue or shared with other non-neuronal tissues. These techniques should facilitate the characterization of antineuronal antibody reactivities and lead to a clearer understanding of their role in the pathogenesis of autoimmune neurologic disease.
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PMID:Antibodies to brain integral membrane proteins in systemic lupus erythematosus. 848 22

Two disease associated lectin-carbohydrate interactions have been studied. (1) A T-cell surface lectin which binds IgA1 and IgD is expressed on CD4+ and CD8+ T-lymphocytes in a number of diseases including systemic lupus erythematosus, rheumatoid arthritis (RA), Behcet's disease and IgA nephropathy. We have demonstrated that calcium independent binding to this receptor is mediated by the O-linked disaccharide Gal beta 3GalNAc which is associated with the hinge regions of both IgA1 and IgD. (2) In rheumatoid arthritis the proportion of IgG0 glycoform populations lacking terminal galactose increases. We have shown that terminal GlcNAc residues on oligosaccharides in the Fc region of IgG0 can bind to the C-type lectin, serum mannose binding protein, and thus activate the classical complement pathway. This provides a mechanism of activation of the complement system not available to the other classes of IgG glycoforms.
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PMID:Lectin-carbohydrate interactions in disease. T-cell recognition of IgA and IgD; mannose binding protein recognition of IgG0. 859 41

The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did not develop overt clinical signs of lupus and nephritis. The pathogenic T cell clones thus reside within the V beta 8.3+ T cell population, which includes an expanded T cell clone described previously. Finally, UDA alters the production of autoantibodies in a sex-dependent manner.
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PMID:Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice. 876 10

Studies conducted in Europe suggest an association between IgG glycosylation abnormalities and rheumatoid arthritis (RA). Glycosylation abnormalities have been shown in other inflammatory diseases such as tuberculosis, systemic lupus erythematosus (SLE) and Crohn's disease. These observations led us to study glycosylation abnormalities among patients with RA and healthy controls in the tropics (sub-Saharan Africa). Using a lectin binding assay, we found that glycosylation differences were present in both groups when compared with British rheumatoid and healthy controls. This suggests that IgG glycosylation abnormalities may occur in association with chronic infections in the tropics.
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PMID:IgG glycosylation in association with tropical infections and rheumatoid arthritis in the tropics. 883 47

Using lectin blots in conjunction with peptide mapping, alpha 2-macroglobulin micropurified from systemic lupus erythematosus (SLE) patients was shown to become abnormally glycosylated suggesting the occurrence of complex glycosylation in this pathological condition. To confirm there is indeed a quantitative increase in specific monosaccharides in this protein; alpha 2-macroglobulin was micropurified from a battery of 37 serum samples which included 6 normal donors (3 male and 3 female), 23 SLE patients, 6 rheumatoid arthritis patients, 1 mixed connective tissue disease patient, and 1 Sjogren's syndrome patient; for carbohydrate analysis. It was noted that the concentration of total monosaccharides in alpha 2-macroglobulin micropurified from serum samples of SLE patients is significantly higher than normal donors with a mean +/- SD of 188 +/- 410 micrograms/mg protein (SLE, n = 23) versus 14.5 +/- 4 micrograms/mg protein (normal, n = 6) even though there was a high variation in the level of monosaccharides among the SLE patients. An increase in oligosaccharides in alpha 2-macroglobulin from SLE patients compared to normal subjects was confirmed by concanavalin A (Con A) blots using peptide fragments derived from the micropurified protein. Since the interaction of peptide fragments derived from alpha 2-macroglobulin with Con A requires the presence of mannose and/or glucose residues, we have also examined if there are any correlations between the levels of mannose and glucose in alpha 2-macroglobulin and SLE. The concentration of mannose (38 +/- 60 micrograms/mg protein) in alpha 2-macroglobulin derived from SLE patients was significantly higher than normal donors (mannose, 4.8 +/- 1 micrograms/mg protein) however, the concentration of glucose in alpha 2-macroglobulin derived from SLE patients when compared to normal donors was not statistically significant, 18 +/- 20 micrograms/mg protein in SLE versus 2 +/- 0.5 micrograms/mg protein in normal donors due to high variation between samples. Also, the concentration of galactose in alpha 2-macroglobulin from SLE patients was significantly higher than normal donors (45.7 +/- 173 micrograms/mg protein versus 0.13 +/- 0.03 microgram/mg protein). These results illustrate quantification of carbohydrate in selected glycoproteins such as alpha 2-macroglobulin may be a novel and alternative clinical marker for SLE.
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PMID:An increase in the carbohydrate moiety of alpha 2-macroglobulin is associated with systemic lupus erythematosus (SLE). 944 26

The distribution of free and HLA-associated human beta 2-microglobulin (beta 2m) in serum, urine, spinal fluid, parotid duct saliva, seminal fluid, amniotic fluid and whey and in membranes from thrombocytes, lymphocytes, neutrophils and fat globules from milk was studied by crossed radioimmunoelectrophoresis (CRIE). The hydrophobic domain of HLA was demonstrable in 'charge-shift CRIE' and by binding to phenyl-Sepharose in 'hydrophobic-interaction CRIE'. In 'lectin-affinity CRIE' with concanavalin A and Lens culinaris lectin Sepharose the carbohydrate moiety present on. HLA exhibited heterogeneity as judged by the appearance of two partly separated protein peaks. Except for isolated fat globule membranes, HLA-associated beta 2m was present on all cells investigated. 'Free' beta 2m did not contain a hydrophobic domain as assessed by charge-shift and hydrophobic-interaction CRIE. All body fluids contained beta 2m in its 'free' form only. In serum, besides the free beta 2m, 2% was present as HLA-associated beta 2m, which, however, did not contain a hydrophobic domain. A degradation product of 'free' beta 2m, with alpha-mobility, was observed in sera from patients with malignant disorders, rheumatoid arthritis or systemic lupus erythematosus.
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PMID:Distribution of 'free' and HLA-associated human beta 2-microglobulin in some plasma membranes and biological fluids. 953 63

The Hakata antigen is a novel, thermolabile beta2-macroglycoprotein that reacts with sera from patients suffering from systemic lupus erythematosus. In this study we present the structure and the function of the Hakata antigen. We have identified cDNA clones encoding the Hakata antigen and analyzed its function. The cDNA included a possible open reading frame of 897 nucleotides, encoding 299 amino acids. The Hakata antigen consisted of a collagen-like domain in the middle section and a fibrinogen-like domain in the COOH terminus, both of which are homologous to human ficolin-1 and opsonin P35, indicating that these three molecules form a distinct family. The molecular mass of the Hakata antigen expressed in transfected cells was 35 kDa under reduced conditions, and it formed ladder bands under nonreducing conditions compatible with the previous result that the Hakata antigen exists in serum as homopolymers. Purified Hakata antigen sustained lectin activity, showing affinity with GalNAc, GlcNAc, D-fucose as mono/oligosaccharide, and lipopolysaccharides from Salmonella typhimurium and Salmonella minnesota. These results suggest that the Hakata antigen, a new member of the ficolin/opsonin P35 family, plays a role in the serum exerting lectin activity under physiological conditions.
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PMID:Cloning and characterization of the Hakata antigen, a member of the ficolin/opsonin p35 lectin family. 969 14


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