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)

Mannose-binding lectin (MBL) is the most intensively studied human collectin. It is recognized to be a versatile macro-molecule with many of the functional characteristics of IgM, IgG and Clq. In the presence of calcium the protein can bind to a wide spectrum of oligosaccharides through multiple lectin domains. Such binding to the repeating sugar arrays on microbial surfaces may result in direct uptake by one or more collectin receptors on phagocyte surface or may trigger the activation of a pro-serine protease complex (MASP 1 and MASP 2) leading to cleavage of C4 and C2 of the classical complement pathway. Although serum levels of MBL are normally rather low (1500 micrograms/litre) there is increasing evidence that the protein plays an important role in immune defence, particularly during the phase of primary contact with a microorganism. This is suggested by the observed association of an increased incidence of infections in individuals with structural mutations in exon 1 of the MBL gene. A cluster of such mutations in codons 52, 54 and 57 lead to secondary structural abnormalities of the collagenous triple helix and a failure to form biologically functional higher order oligomers. The codon 54 mutation has been identified in several Eurasian populations whereas the codon 57 mutation is characteristic of sub-Saharan populations. One intriguing paradox arising from the MBL genotyping studies is the observation that in many populations there are surprisingly high frequencies of either the codon 54 or codon 57 mutation, suggesting that there may be some biological advantage associated with absence of the protein. Nevertheless, various groups have reported either low serum levels of MBL or an increased frequency of the structural gene mutations in patients with suspected immunodeficiencies, those with frequent unexplained infections and those with systemic lupus erythematosus. There is also evidence that the rate of progression of AIDS in HIV positive men is faster in those with such mutations. A recently published study of a consecutive series of admissions to a paediatric unit suggests that children presenting with an infectious aetiology are significantly more likely to have a MBL mutation. Moreover, this association was independent of age. Prospective studies are underway to address the questions raised by these findings.
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PMID:Mannose-binding lectin (MBL) in health and disease. 977 16

Galactose-free immunoglobulin G (IgG), which is known to be higher in the sera of patients with rheumatoid arthritis, was prepared from IgG of healthy volunteers using enzymes. Its reactivity to lectins was analyzed. The galactose-free IgG showed no reactivity to Ricinus communis agglutinin 120 but displayed greater reactivity to concanavalin A and Lens culinaris lectin than did intact human IgG. Then, IgG in serum samples was bound to protein A immobilized on a nitrocellulose membrane, and its reactivity to biotinylated concanavalin A was measured with streptavidin-conjugated horseradish peroxidase. When the reactivity to concanavalin A of IgG in sera from healthy individuals and patients with rheumatoid arthritis (RA), osteoarthritis, systemic lupus erythematosus, or hepatic disease was compared, higher levels were shown in patients with RA, notably in 60% of the seronegative patients and 80% of the early phase patients. Therefore, it was suggested that augmentation of the abnormal IgG in sera was highly specific to patients with RA and that this novel serum test could be very useful for an accurate diagnosis of this disease.
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PMID:Detection of disease-specific augmentation of abnormal immunoglobulin G in sera of patients with rheumatoid arthritis. 1005 97

The elevated expression of IL-6 and IL-10 may have an important role in SLE pathogenesis. IL-6 production by normal monocytes can be inhibited by IL-10, and it has been suggested that SLE monocytes are refractory to this negative signal. To examine this possibility, the effects of regulatory factors on IL-6 expression by SLE PBMC (N = 51) were compared to effects on control PBMC (N = 21). We found that (1) exogenous rIL-10 and rIL-4 mediated reduction of constitutive and lectin-induced IL-6 in monocytes of SLE patients as effectively as that of controls; (2) IL-6 mRNA decay was significantly delayed in SLE with active disease (P < 0.001); (3) adding rIL-10 or neutralizing endogenous IL-1 beta and TNF-alpha down-regulated IL-6 mainly by destabilizing IL-6 transcripts, whereas exogenous IL-4 and TGF beta 1 down-regulated IL-6 transcriptionally; (4) time kinetics and levels of IL-10 were lower than those of IL-6 and IL-1 beta. Thus, contrary to a previous report, IL-6 production by SLE PBMC responds normally to regulatory signals, and the IL-6 overexpression in SLE may be due, at least in part, to the kinetics and availability of regulatory cytokines.
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PMID:Exogenous IL-10 and IL-4 down-regulate IL-6 production by SLE-derived PBMC. 1021 49

Hakata antigen was first reported as a serum protein that reacted with an autoantibody from patients with systemic lupus erythematosus. Recently, it has been found that Hakata antigen is a new member of the ficolin/opsonin p35 family, which is a distinct lectin family, on the basis of homology of structures and the common characteristic of possessing lectin activity. In this study we analyzed the tissue distribution of Hakata antigen. Hakata antigen mRNA and protein were generated in the lung and liver. In the lung, Hakata antigen was produced by both ciliated bronchial epithelial cells and Type II alveolar epithelial cells and was secreted into the bronchus and alveolus. In the liver, Hakata antigen was produced by bile duct epithelial cells and hepatocytes and was also secreted into the bile duct. These results demonstrate that Hakata antigen is a unique lectin protein that exists not only in serum but also in bronchus/alveolus and bile, and indicate that Hakata antigen plays a role in bronchus/alveolus and bile under physiological conditions.
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PMID:Hakata antigen, a new member of the ficolin/opsonin p35 family, is a novel human lectin secreted into bronchus/alveolus and bile. 1033 Apr 54

The objectives were to provide estimates of the prevalence of autoantibody (Ab) directed to CD45 in lupus patients, identify the target autoantigen(s), and determine the ability of such reactivity to mediate neutralization of T lymphocytes. Sera from 64 patients were studied using 2 assays: Western blot and an ELISA with CD45 eluted from 3 cell lines as antigen (U937, Jurkat and Daudi). The role of carbohydrate specificity was investigated using enzyme digestion of blotted glycans, competition with sugars, and inhibition with lectins. Apoptosis was studied through annexin V binding, and cell cycle analysis using the propidium iodide method. AutoAb to CD45 were detected in 16/64 sera (25%) by Western blot, and 21/32 sera (66%) found positive in the ELISA. CD45 purified from Daudi cells was identified in the ELISA, but not in the blot. AutoAb were of the IgM and the IgG isotypes, but not specific for a particular cell type or CD45 isoform: 2 dominant specificities were recognized, one against p180, and another against high MW isoforms. Neuraminidase-induced enhancement of reactivity, together with the inhibitory effect of N-acetyl galactosamine and Dolichos diflorus lectin suggest that the epitopes are carbohydrates. AutoAb which were specific for activated CD4+T cells triggered the annexin V binding, and, in 2 of 4 cases, lymphocytes underwent apoptosis. In conclusion, carbohydrate conformational epitopes may be important as target antigens, and some CD45 autoAb have the capacity to neutralize activated T cells through anergy or apoptosis.
Lupus 2000
PMID:CD45 autoantibodies mediate neutralization of activated T cells from lupus patients through anergy or apoptosis. 1103 38

Mannose-binding lectin (MBL), a serum protein characterised by both collagenous regions and lectin domains, plays an important role in innate immune defence. It binds to the repeating sugar arrays on many microbial surfaces through multiple lectin domains and, following binding, is able to activate the complement system via an associated serum protease, MASP-2. Serum levels of MBL are influenced by three mutations clustered in exon 1 of the gene and are further modulated by various promoter region polymorphisms. The exon 1 mutations lead to secondary structural abnormalities of the collagenous triple helix and a failure to form biologically functional higher order oligomers. There is an increased incidence of infections in individuals with such mutations and an association with the autoimmune disorders SLE and rheumatoid arthritis. Nevertheless, MBL genotyping of various populations has led to the suggestion that there may be some biological advantage associated with absence of the protein. These and other findings suggest that the concept of MBL as a protein involved solely in first line defence is an oversimplification and the protein should rather be viewed as having a range of activities including disease modulation.
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PMID:Mannose-binding lectin: structure, function, genetics and disease associations. 1125 42

Three pathways are recognized in complement activation. The aim of our study is to elucidate immunohistologically which complement pathway is associated with complement activation in immunoglobulin A (IgA) glomerulonephritis (GN) and which IgA subclass is related to complement activation. Immunohistological staining was performed on renal biopsy specimens obtained from 36 patients with IgA GN, 10 patients with systemic lupus erythematosus (SLE), and 16 patients with other GNs using polyclonal antibodies of IgG, IgA, IgM, C1q, C3c, and C4 and monoclonal antibodies of IgA1, IgA2, mannose-binding lectin (MBL), and MBL-associated serine protease-1 (MASP-1). Mesangial deposits of both IgA1 and IgA2 were found in 19 of 36 patients with IgA GN. Mesangial deposits of C3c, C4, MBL, and MASP-1 also were detected in these 19 patients, and IgA2, MBL, and MASP-1 deposits were colocalized in the mesangium in these patients. The remaining 17 patients showed mesangial deposits of IgA1 alone. Twelve of these 17 patients showed mesangial deposits of C3c without C4, MBL, or MASP-1. No deposition of C1q was evident in patients with IgA GN. Three of 10 patients with SLE showed glomerular deposition of MBL and MASP-1 without glomerular deposition of IgA2. None of the patients with other GNs showed glomerular deposition of IgA1, IgA2, MBL, or MASP-1. There was no correlation in clinical or pathological indicators between IgA2-positive and IgA2-negative patients with IgA GN. In conclusion, alternative pathway-involved complement activation is associated with mesangial deposits of IgA1 alone in patients with IgA GN. In those with mesangial deposits of both IgA1 and IgA2, both the alternative and lectin pathways are involved in complement activation. We first report that mesangial deposits of IgA2 may activate the lectin pathway in patients with IgA GN.
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PMID:Mesangial IgA2 deposits and lectin pathway-mediated complement activation in IgA glomerulonephritis. 1168 63

Complement is involved in inflammation and in the optimization of adaptive responses. Abnormalities in the complement system have been associated with autoimmunity, especially systemic lupus erythematosus. A paradoxic relation exits between complement and lupus. Complement-mediated tissue damage is accepted as a mechanism in disease pathophysiology. Conversely, complement exerts a protective effect in disease development. The theoretic framework explaining this protective influence involves the adequate disposal of apoptotic material by classic pathway components. Inadequate clearance of apoptotic material may evoke a proinflammatory autoimmune response. This conceptual model is substantiated by studies indicating that complement receptor genes are within major susceptibility loci of systemic lupus erythematosus, that functional and structural abnormalities in these receptors are found in lupus mouse models, and that genetic polymorphism of lectin pathway genes correlates with increased risk of disease development. Finally, new diagnostic and therapeutic modalities based on complement regulation have been described in the past year.
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PMID:Update on complement in the pathogenesis of systemic lupus erythematosus. 1219 43

Systemic lupus erythematosus is an autoimmune disease primarily affecting women. Currently, systemic lupus erythematosus therapy is suboptimal due to adverse effects of immunosuppressants, particularly corticosteroids. This study determines the single effects of prednisolone, dehydroepiandrosterone, bromocriptine, tamoxifen, mycophenolic acid, 2-chloro-2'-deoxyadenosine, azathioprine, and chloroquine on lectin-stimulated proliferation of human T lymphocytes, as well as determining whether there are interactions in the joint effects of prednisolone and these agents. The T lymphocytes from the whole blood of 10 middle-aged women were stimulated by phytohemagglutinin and cultured with varying drug concentrations. The Hill function was used to evaluate single-drug response data. Isobolograms were constructed to qualitatively analyze interactions. Parametric analysis based on competitive and noncompetitive interaction models was further applied to quantify the joint interactions and predict steroid-sparing potential. The surface interaction parameter (psi) estimated from parametric analysis was in concordance with isobolographic inspection for all interactions studied. All interactions favored the noncompetitive model. Results suggest that dehydroepiandrosterone is additive in its effect with prednisolone, whereas tamoxifen interacts synergistically, both providing steroid-sparing effects. Novel immuno-suppressants such as mycophenolic acid may still provide added pharmacologic benefit during therapy despite a slight antagonistic interaction with prednisolone. These studies help rationalize actual or potential use of other drugs with prednisolone in the treatment of systemic lupus erythematosus.
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PMID:Interactions of prednisolone and other immunosuppressants used in dual treatment of systemic lupus erythematosus in lymphocyte proliferation assays. 1531 31

In many pathological states changes in the carbohydrate part of serum glycoproteins occur, the etiopathogenic role or diagnosis significance of these abnormally glycosylated glycoproteins being relevant in many instances. The aim of this study was to determine the glycosylation pattern of the serum immunoglobulin A (IgA) in young women suffering from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), by comparison with that in healthy ones. We used lectin proteins as bivalent reagents to selectively and specifically recognize and bind the different oligosaccharides at the surface of the IgA molecules and precipitate them. The serum IgA level in the SLE and RA women included in this study was of 4 and respectively 6 times greater than in control women. Our experiments revealed for the IgA isolated from SLE women a very low degree of glycosylation, as follows: in the Fc region, we detected a markedly reduced level of the unbisected, biantennary oligosaccharides (by 72.8%) and of the unbisected, tri- and tetraantennary oligosaccharides (by 40%), accompanied by a slightly increased level of the bisected (by 14.7%) and fucosylated (by 13.3%) oligosaccharides; in the hinge region, a marked degalactosylation (by 74.4%) of the oligosaccharides was revealed; the sialylation degree of the IgA molecules was thus reduced by 71.2%. Related to it, it is reasonable to presume a certain role of the degalactosylated IgA fraction in renal tissue deposition of IgA in SLE patients, as it has been ascribed to this fraction in IgA nephropathy. Referring to the IgA isolated from RA women, we showed that it selectively bound the lectins, but lacked the property to be lectin-precipitated, most probably due to an altered arrangement of the oligosaccharide chains at the surface of the glycoprotein.
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PMID:Lectin-binding profile of serum IgA in women suffering from systemic autoimmune rheumatic disorders. 1552 74


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