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)

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

Anti-centromere antibody (ACA) have been recognized in sera of patients with primary biliary cirrhosis (PBC) and CREST syndrome. The major reactive antigen of ACA have been identified as CENP-B (80kDa). Using an indirect immunofluorescence (IIF) method and ELISA method, we detected ACA and anti-CENP-B antibody in patients with PBC and various liver diseases and collagen diseases. We tested sera of 44 patients with PBC, 8 patients with autoimmune hepatitis (AIH), 51 patients with chronic hepatitis B (CH-B), 312 patients with chronic hepatitis C(CH-C), 12 patients with progressive systemic sclerosis (PSS), 10 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis (RA), and 30 with healthy subjects (HS). ACA was detected by IIF technique, using HEp-2 cell and fluoro-CENTRO slides (MBL) as substrates. Anti-CENP-B antibody was detected by ELISA method using recombinant CENP-B (MBL) as the antigen. ACA was detected in sera of 12 (27%) patients with PBC, two (25%) patients with AIH, five (2%) patients with CH-C, nine (75%) patients with PSS, and one (10%) patients with RA. ACA was not detected in sera of patients with CH-B and SLE and in HS. The results of IIF test for ACA, using HEp -2 cells and fluoro-CENTRO slides, were completely agreed. Anti-CENP-B antibody was detected in 28(97%) out of 29 patients sera positive for ACA. The titers of ACA and anti-CENP-B antibody did not show a correlation (r = 0.24). Out of 12 sera, in which, the titers of anti-CENP-B antibody was over 400. Among them, eight were patients with PBC and four were PSS. Later, out of four patients with PSS, three (75%) were found to be positive for anti-mitochondrial antibody. Out of five patients, in which the titer of anti-CENP-B antibody showed over 800, all were patients with PBC. The titers of ACA have no relationship with PBC. However, the titers of anti-CENP-B antibody have closed relationship with PBC. The reason why the titers of ACA and anti-CENP-B antibody were not correlated is unknown. We consider anti-CENP-B antibody is a new marker of a subset of PBC, because almost all the patients were PBC when this antibody showed over 400.
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PMID:[Clinical significance of anti-centromere antibody and anti-CENP-B antibody in sera of patients with primary biliary cirrhosis]. 891 Oct 74

Mannose-binding lectin (MBL; also known as mannan-binding lectin) is an important component of innate immunity. MBL levels are mainly genetically determined. Low serum MBL levels and their cognate haplotypes have been associated with a wide range of infections. However, most subjects with MBL deficiency remain healthy. MBL deficiency is also associated with non-infectious diseases including systemic lupus erythematosus, rheumatoid arthritis, cystic fibrosis and common variable immunodeficiency. MBL deficiency may affect susceptibility to (e.g. meningococcal disease), or alter the natural history of (e.g. rheumatoid arthritis, cystic fibrosis), a disease. MBL (plasma-derived or recombinant) therapy has yet to be shown to be safe and effective. Potentially it may be useful in MBL-deficient patients to reduce susceptibility to, or enhance recovery from, bacterial infection or to alter the natural history of a disease (disease-modifying drug). In practise the place of MBL therapy may be as a disease-modifying drug to reduce the severity of rheumatoid arthritis and to preserve lung and liver function in cystic fibrosis. MBL therapy may also ameliorate various immunodeficiency syndromes. A potential hazard of MBL therapy is enhanced complement-mediated host damage. The place of MBL therapy will await results of randomized controlled clinical trials.
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PMID:Clinical potential of mannose-binding lectin-replacement therapy. 1288 1

Autoantibodies to the three ribosomal phospho (-P) proteins P0, P1, P2, referred to as Rib-P, are specifically found in 10-40% of patients with systemic lupus erythematosus. The variations in the observed frequency of these autoantibodies is related to a number of factors such as the test system used to detect the antibodies. Several immunoassays that were designed for research and diagnostic laboratory use have been developed. The autoantigens employed in these tests include native proteins, recombinant polypeptides, and synthetic peptides. In this study, we compared the technical and clinical accuracy of anti-Rib-P antibody assays from different commercial suppliers including ELISA systems and a novel addressable laser bead assay (from Euroimmun, MBL, Pharmacia Diagnostics, INOVA). Although the assays from all suppliers used in this study performed well in the technical part of the study, relatively poor correlations and significant differences in the clinical accuracy were found. Based on the results, we conclude that the detection of anti-Rib-P antibodies strongly depends on both the nature of the antigen and the detection system. We recommend that anti-Rib-P assays should be standardized on an international level. The Varelisa Rib-P profile and the addressable laser bead Rib-P assays represent promising tools and platforms for the detection of anti-Rib-P antibodies in the future.
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PMID:Technical and clinical evaluation of anti-ribosomal P protein immunoassays. 1520 13

In systemic lupus erythematosus (SLE), hypocomplementaemia and complement deposition have been described both in man and in experimental models. A major involvement of the classical pathway of complement activation has been demonstrated in this disease, however relatively little is known about the involvement of the lectin pathway. Therefore in the present study we have analyzed the activity of all three pathways of complement activation in murine models of SLE. In the mouse, MBL is expressed in two forms, namely MBL-A and MBL-C. In the present study young and old MRL-lpr and control MRL+/+ mice were compared for the levels of complement activity with specific attention for the lectin pathway. It was found that upon aging of both MRL-lpr and MRL+/+ mice, a marked decrease in the activity of the classical pathway (CP) occurs. Levels of alternative pathway (AP) and lectin pathway (LP) activity remain unchanged. Key-molecules of these pathways, C1q, C3, MBL-A and MBL-C were analyzed and were all found to be decreased in aged mice of both strains. The levels of MBL-A and MBL-C showed a high degree of correlation and decreased equally. In aged MRL-lpr mice in which autoimmunity is most pronounced, we observed high autoantibody titers and strong deposition of glomerular immune complexes in association with deposition of C1q, C3, MBL-A and MBL-C. In conclusion, these data suggest that in addition to the classical pathway and the alternative pathway also the lectin pathway of complement activation is involved in murine lupus nephritis.
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PMID:Activation of the lectin pathway in murine lupus nephritis. 1578 Nov 17

Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging from a Swedish study of C2 deficiency, a deficiency with an estimated prevalence of about 1/20,000 in Western countries, less than 10% of the deficiencies of the classical and alternative pathways and the late complement components are identified in Sweden. C1 inhibitor deficiency and deficiencies of MBL and MASP-2 were not included in the assessment. The introduction of new screening methods should facilitate detection of complement deficiencies in clinical practice. In our study of C2 deficiency (n=40), 57% of the patients had a history of invasive infection with encapsulated bacteria, mainly Streptococcus pneumoniae. This emphasizes the importance of the classical and/or the lectin pathway in defence against severe infection. Rheumatological disease, mainly systemic lupus erythematosus was present in 43% of the patients. In addition, a significant association was found between C2 deficiency and atherosclerosis. Complement-dependent disease mechanisms are discussed together with the potential importance of non-complement genes for disease expression in complement deficiencies. Analysis of larger patient groups is required in order to establish guidelines for investigation and treatment of patients with complement deficiency.
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PMID:Complement deficiency and disease: an update. 1602 38

Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE.
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PMID:Infections and SLE. 1637 52

Apoptosis, followed by rapid phagocytic clearance, is the primary mechanism by which organisms dispose of unwanted cells. The intracellular and extracellular composition of an apoptotic cell changes to decrease immunogenicity and enhance its uptake. By changing their extracellular composition, apoptotic cells acquire the capacity to bind complement initiation molecules such as C1q and MBL. Binding of these molecules can lead to complement activation. Membrane bound complement inhibitors are down-regulated during apoptosis, which would leave the cell less protected against complement activation; however, recent data show that fluid-phase complement inhibitors may compensate for this loss of regulation. Importantly, binding of complement is a process that mainly takes place during the late stages of apoptosis. Most cells will be cleared before that stage under steady state conditions, but during overwhelming apoptosis or impaired phagocytosis, apoptotic cells may remain in tissues for a longer time and acquire complement proteins. Based on the data from deficiencies of early complement components and the development of systemic lupus erythematosus with accumulation of dead cells, it is clear that, under certain conditions, apoptotic cells persist, becoming necrotic and overloading the scavenging capacities of the complement system. Although the complement system is also involved in inducing apoptosis in target cells, this review will focus on the role of complement in the clearance of apoptotic cells.
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PMID:Role of complement and complement regulators in the removal of apoptotic cells. 1796 51

Deficiencies of complement proteins of the classical pathway are strongly associated with the development of autoimmune diseases. Deficiency of C1r has been observed to occur concomitantly with deficiency in C1s and 9 out of 15 reported cases presented systemic lupus erythematosus (SLE). Here, we describe a family in which all four children are deficient in C1s but only two of them developed SLE. Hemolytic activity mediated by the alternative and the lectin pathways were normal, but classical pathway activation was absent in all children's sera. C1s was undetectable, while in the parents' sera it was lower than in the normal controls. The levels of C1r observed in the siblings and parents sera were lower than in the control, while the concentrations of other complement proteins (C3, C4, MBL and MASP-2) were normal in all family members. Impairment of C1s synthesis was observed in the patients' fibroblasts when analyzed by confocal microscopy. We show that all four siblings are homozygous for a mutation at position 938 in exon 6 of the C1s cDNA that creates a premature stop codon. Our investigations led us to reveal the presence of previously uncharacterized splice variants of C1s mRNA transcripts in normal human cells. These variants are derived from the skipping of exon 3 and from the use of an alternative 3' splice site within intron 1 which increases the size of exon 2 by 87 nucleotides.
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PMID:Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. 1806 8

The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematosus susceptibility, but studies in Brazilian population have not been conducted. To examine potential associations of mannose-binding lectin alleles G57E, G54D, IVSnt5, R52C and R52H with susceptibility to and clinical expression of systemic lupus erythematosus in southern Brazilian patients, we conducted a case-control study with 327 consecutive patients with diagnosis of systemic lupus erythematosus and 345 healthy controls. Genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction assay. A statistically significant difference in the frequencies of allele R52C was observed in European-derived systemic lupus erythematosus patients when compared with controls (9.6% vs. 3.3%, p < 0.001, odds ratio: 3.15, 95% confidence interval: 1.76-5.62, p < 0.05). The frequencies of alleles G54D and G57E were not different between European-derived systemic lupus erythematosus patients and controls. There were no differences between clinical and laboratory features in systemic lupus erythematosus patients according to the presence or absence of mannose-binding lectin allelic variants. These results support an increased risk of systemic lupus erythematosus in European-derived individuals carrying allele R52C. Patients carrying this allele have an approximately three-fold higher odds ratio of developing systemic lupus erythematosus when compared with controls. Our data do not support associations between the mannose-binding lectin allelic variants studied and clinical expression of systemic lupus erythematosus.
Lupus 2010 Mar
PMID:Mannose-binding lectin gene polymorphisms in Brazilian patients with systemic lupus erythematosus. 2002 98


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