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)

The inhibition of immune precipitation is mediated by the classical complement pathway. We report here that the rate of precipitate formation depends on the genetic form of human C4 present during immune precipitation. C4A3 is more effective than C4B1 in its capacity to inhibit the rate of immune precipitate formation in serum and in serum-free reaction mixtures containing C1 and C4. Immune precipitates form within seconds after antigen is mixed with antibody, and the activation of the classical pathway is known to occur within seconds after C1 binds to antibody molecules. The covalent deposition of C4b on immune complexes is an essential step in the inhibition of immune precipitate formation, and if any of the reactions that lead to covalent C4b deposition become limiting, the rate of immune precipitation could exceed the complement system's inhibitory capacity. Hence, the inhibition of this rate may be an important function underlying the complement-mediated processing of immune complexes, and a decreased ability of the complement system to mediate this process in the presence of C4B1, in contrast to C4A3, could explain, at least in part, the association between the C4A-null phenotype and autoimmune diseases such as systemic lupus erythematosus.
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PMID:C4-mediated inhibition of immune precipitation and differences in inhibitory action of genetic variants, C4A3 and C4B1. 318 Jul 39

We describe an ELISA for assessment of complement function based on the capacity of serum to support fixation of complement components to solid phase immune complexes (IC). Microplates were coated with aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA IgG. The solid phase IC were reacted with human serum. The uptake of C3b, C4b and properdin was measured using biotinylated F(ab)2 antibodies to each of the proteins, avidin alkaline phosphatase, and paranitrophenyl phosphate. Serial samples obtained from 15 patients with systemic lupus erythematosus were investigated. Out of 72 sera, 24 showed a reduced capacity to support incorporation of C4b into solid phase IC. Thirty-one of the sera showed low C3b binding and 59 of the sera a reduced uptake of properdin. The incorporation into solid phase IC of C3b and C4b as well as of C3b and properdin were closely correlated at high disease activity. In general, patients with severe disease manifestations showed low values in the uptake assays. Judging from the results obtained by analysis of serial samples, the uptake of C3b, C4b and properdin, complement mediated solubilization of fluid phase IC and the concentrations of C1q binding IC were useful indicators of disease activity in the patients. The concentrations of circulating C4, C3 and properdin varied less consistently according to disease activity. The concentrations of serum properdin were never found to be low, which was in contrast to the finding of reduced properdin uptake by solid phase IC in most of the samples.
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PMID:Complement fixation by solid phase immune complexes. Reduced capacity in SLE sera. 326 27

We developed a quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of C4b.C4-bp complex by incubating the sample on anti-C4-bp-coated plate and then developing with HRP-labeled anti-C4. The amount of C4b.C4-bp complex, generated in vivo by the interaction of purified C4b with C4-bp or normal human serum with aggregated human IgG, was measured by the ELISA. The complex, however, rapidly decreased in serum by the action of factor I. Six out of the 100 plasma samples from patients with various diseases were found positive in the ELISA. One plasma sample from a patient with SLE showed high level of C4b.C4-bp complex with decreased levels of factor I, C4, C4-bp and CH50. These results suggest that the detection of C4b.C4-bp complex is useful for monitoring the diseases in which the classical pathway activation is expected.
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PMID:Determination of C4b.C4-bp complex formed by the activation of classical complement pathway using an enzyme-linked immunosorbent assay. 350 Feb 39

A relationship was found between the sums of the component proteins of the classical pathway C3 convertase (C2 and C4) and their regulators (C4bp and 1) in 184 normal controls. The relationship was maintained in most patients with low levels of individual components resulting from congenital deficiency and urinary losses, as well as in most cord sera. On the other hand, classical pathway activation in membranoproliferative glomerulonephritis type I, systemic lupus erythematosus, hereditary angioneurotic edema, and bacteremia resulted in loss of this relationship. Patients with alternative pathway-mediated complement activation (membranoproliferative glomerulonephritis type II) had a normal relationship between the classical component and regulatory proteins. In situations in which classical pathway activation is suspected, simultaneous examination of C4, C2, C4bp, and I may be helpful.
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PMID:Relationship between the component and regulatory proteins of the classical pathway C3 convertase. 363 65

It has been claimed that patients with systemic lupus erythematosus (SLE) have an inherited deficiency of erythrocyte complement receptor type 1 (CR1, with ligand binding specificity for C3b, iC3b and C4b). CR1 functions as the only cofactor for factor I-mediated cleavage of iC3b to C3c and C3dg. The activity of this receptor on red cells may be an important mechanism for handling immune complexes which have bound C3b or iC3b. Radioligand binding studies were performed using a monoclonal antibody to CR1, E11, to enumerate these receptors accurately. The results confirmed that patients with SLE have a reduced number of CR1 molecules per red cell, but showed no reduction in CR1 levels amongst their consanguineous relatives. Study of 13 normal families suggested the presence of heritable factors controlling the numbers of erythrocyte CR1 molecules; in particular there was a correlation between mean parental CR1 numbers and CR1 numbers in their children. However, amongst 17 families of 19 patients with SLE, four families were identified in which genotypically 'high CR1' SLE patients had persistently low phenotypes. This is not compatible with the hypothesis that the reduction in erythrocyte CR1 numbers in these patients is inherited.
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PMID:Family studies of erythrocyte complement receptor type 1 levels: reduced levels in patients with SLE are acquired, not inherited. 398 91

A 29-yr-old woman with systemic lupus erythematosus (SLE) was found to have no detectable C3b/C4b receptors (CR1) on her erythrocytes (E) when they were assayed by the binding of rabbit polyclonal and murine monoclonal (Yz-1) anti-CR1. Analysis by two-color fluorescent flow cytometry of CR1 expression on the patient's B lymphocytes that had been stained indirectly with monoclonal anti-B1 and rabbit F(ab')2 anti-CR1 also revealed a marked deficiency of CR1. Total cellular CR1 of neutrophils, assessed by a sandwich radioimmunoassay, was about half that of neutrophils from normal individuals. Because her E had expressed 173 sites/cell 2 yr before, the CR1 deficiency was considered to be acquired and a possible mechanism was sought. Autoantibody to CR1 was measured by a radioimmunoassay in which serum or its fractions were incubated in microtiter wells that had been coated with purified CR1, and binding of immunoglobulin to the wells was quantitated with 125I-labeled goat IgG antihuman F(ab')2. The CR1-specific binding of immunoglobulin from the patient's serum was 19.1 ng/well of the detecting antibody when her E had eight CR1 sites per cell; that of 28 healthy donors was 1.3 +/- 0.5 ng/well (mean +/- SEM), and that of 34 additional patients with SLE was 0.5 +/- 0.3 ng/well. The activity was present also in purified IgG and its F(ab')2 fragment, indicating that the binding of serum immunoglobulin to CR1 was not mediated by C3 fragments. The specificity of the patient's IgG for CR1 was confirmed when pretreatment of the CR1-coated wells with affinity-purified rabbit F(ab')2 anti-CR1 was shown to inhibit by 68% the binding of the IgG. The autoantibody also interacted with CR1 in cell membranes, as assessed by its capacity to inhibit the binding of indirectly fluoresceinated Yz-1 to neutrophils, and, when combined with goat IgG antihuman F(ab')2, to diminish the binding of dimeric C3b to normal E. During the period of the marked deficiency of CR1 the patient experienced an exacerbation of disease activity which was treated with prednisone. Clinical improvement was accompanied by a decrease in the serum concentration of anti-CR1 to levels present 2 yr earlier, and an increase of CR1 to 170 sites/E. The temporal association between high titers of an autoantibody to CR1, absence of CR1 from E, and heightened activity of SLE suggest that the former may have had a role in the other manifestations of the patient's disease.
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PMID:Autoantibody to the C3b/C4b receptor and absence of this receptor from erythrocytes of a patient with systemic lupus erythematosus. 401 77

The complement receptor for C3b of the epithelial cells of human glomeruli is structurally and functionally very similar or identical to CR1, the complement receptor for C3b and C4b present on the membrane of red cells and leukocytes. Four monoclonal antibodies directed against separate epitopes of CR1 react with an antigen in the glomeruli, which appears to be present on the epithelial podocytes. Moreover, the monoclonal antibodies very effectively inhibit the binding of C3b-bearing red cells to the glomeruli. The pattern of immunofluorescence of the receptor was normal or slightly altered in patients with minimal change disease, mesangial proliferative glomerulonephritis (GN), or idiopathic membranous GN. Glomeruli with endocapillary proliferation showed some attenuation of staining. Glomeruli in which the capillary tuft architecture was altered, or of patients with systemic lupus erythematosus, or of patients with diffuse diabetic nephropathy tended to have few foci or no staining for the receptor. No correlation was found between the intensities of staining of the C3b receptor and of C3 antigen deposited in the glomeruli.
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PMID:Monoclonal antibodies to human complement receptor (CR1) detect defects in glomerular diseases. 622 55

Serum concentrations of C1q, C4, C4 binding protein (C4bp), C3 and C2 haemolytic activity have been measured in 110 samples from 20 patients with systemic lupus erythematosus (SLE). Significant reductions in comparison to normal levels were found in the mean serum concentrations of C4, C3 and C4bp as well as C2 haemolytic activities. For patients serum concentrations of C4 correlated with C2 haemolytic activities (r = 0.91) and C4bp (r = 0.79); the C2 haemolytic levels correlated with the concentration of C4b (r = 0.72). It is concluded that serum concentrations of the complement components C4 and C2, which are the constituents of the classical pathway C3 convertase, are regulated by C4bp in vivo. Further metabolic studies are required to determine the causes of decreased serum concentrations of C4bp in patients with SLE.
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PMID:Relative importance of C4 binding protein in the modulation of the classical pathway C3 convertase in patients with systemic lupus erythematosus. 660 10

This study reports quantitative information on the concentration of complement receptor for C3b and C4b (CR1) on erythrocytes from normal individuals and patients with immune complex disease. The measurements were performed by an immunoradiometric assay using monoclonal antibodies against CR1. The antibody specificity was confirmed by immunoprecipitation of CR1 from extracts of surface-labeled cells, by inhibition of rosette formation between B lymphocytes and the erythrocytes intermediate EAC14oxy23b, and by the characteristic distribution of the antigen among cells of human peripheral blood. The number of CR1 molecules in erythrocytes from 52 normal individuals was estimated as 1,410 +/- 620. No significant differences in CR1 levels were observed when individuals were grouped by sex, age, or blood groups. In patients with SLE and rheumatoid arthritis, the number of CR1 molecules per RBC was significantly lower, i.e., 600 +/- 307 and 903 +/- 417, respectively. CR1 levels were normal in asthmatics undergoing long-term treatment with prednisone. In SLE patients, significant correlations were found between CR1 levels, C4 hemolytic titers, and levels of circulating immune complexes. In two out of four patients with SLE, CR1 levels increased significantly during remission, showing that the deficiency is, at least in part, reversible. The deficiency in CR1 could be genetically controlled or could represent an epiphenomenon caused by the interaction of the receptor with a ligand present in the circulation of patients.
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PMID:Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus. 697 75

The influence of serum on phagocytosis related to the complement system was examined by means of a kinetic phagocytosis method using IgG-coated particles, isolated polymorphonuclear neutrophil leucocytes (PMNs), fresh serum, in vitro activated sera and in vivo activated sera. The previously described opsonic properties of C3b and C4b were confirmed by the enhancement of phagocytic rate by the opsonization of IgG particles with C3 and C4. An anti-opsonic effect of serum was revealed by the initial inhibition of PMN phagocytosis of IgG-coated particles in the presence of fresh serum. In vitro activated norma fresh serum and in vivo activated SLE sera mediated a prolonged or even irreversible inhibition of phagocytosis dependent on the degree of complement activation. Investigation of this anti-opsonic effect of serum, which was heat-labile, suggested that it was caused by an inhibition of the interaction between the Fc receptor and IgG mediated by the C1q component of the C1 complex.
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PMID:Kinetic studies of phagocytosis. III. The complement-dependent opsonic and anti-opsonic effects of normal and sle sera. 698 89


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