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)

Although positive direct Coombs' tests occur in most patients with active systemic lupus erythematosus (SLE), haemolytic anaemic associated with antibody to erythrocytes (E) occurs in less than 10%. Our studies show an association between positive direct Coombs' tests and both the presence of circulating immune complexes and diminished activity of the C3b receptor (CR1) of E. Data presented in this report suggest that in vivo binding of immune complexes and complement by the CR1 of E results in positive direct Coombs' tests in the absence of antibody to E. These observations explain the low frequency of haemolytic anaemia compared with the high frequency of direct positive Coombs' tests in patients with SLE.
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PMID:Relationships between C3b receptor (CR1) activity of erythrocytes and positive Coombs' tests. 294 Sep 81

Activation of the complement cascade leads to the generation of multiple breakdown products which bind on to specific cellular receptors and regulate their function. In this review, we describe the biochemical and physiological features of the 7 known complement receptors. Four of them (complement receptors 1, 2, and 3 and receptors for C3a) bind cleavage fragments of the third component of the complement and three have specificity for C1q, factor H and C5a. In patients with systemic lupus erythematosus, a unique human autoimmune disorder, the numbers of CR1 on the surface of the red blood cells are decreased; in this review we discuss the implications in the pathogenesis of SLE. A number of patients have now been reported whose cells lack CR3 from their surface; this deficiency is associated with a number of immune cell dysfunctions which are discussed in detail. Finally, we discuss aberrations in the expression of complement receptors in certain human leukemic cells.
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PMID:The biology and pathophysiology of complement receptors. 294 15

Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal. In 112 patients with SLE, the mean number of CR1 sites on erythrocytes was decreased to 62% of the mean for normal individuals (p less than 0.001). No correlation was found between CR1 expression on erythrocytes and the presence or immunohistopathological type of glomerulonephritis in biopsy specimens from these patients. The mean number of CR1 on erythrocytes of 29 patients with non-SLE glomerulonephritis was slightly decreased to 89% of the normal mean (p greater than 0.05), which could not be attributed to glomerular immune complex disease or vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence or severity of SLE nephritis. 294 97

The microtiter plate ELISA using monoclonal antibody is a specific, sensitive and quantitative technique for measuring CR1 on human erythrocytes. The present investigations established that receptor occupancy by immune complexes did not affect the measurements. The monoclonal anti-CR1 antibody To5 bound unimpeded to receptors that had reacted with an excess of complement-opsonized tetanus toxoid anti-tetanus toxoid complexes prepared at antigen:antibody ratios between 32:1 and 1:8. The CR1 levels on erythrocytes from 11 patients with systemic lupus erythematosus (SLE) were not increased (P greater than 0.30) after release of CR1-bound immune complexes by incubation with factor I. Neither did the serum from these patients contain blocking anti-CR1 activity (P greater than 0.10). Additionally, the number of antigenic CR1 sites in 10 normals and in the 11 patients with SLE was well correlated with the number of functional receptor sites as assessed by binding of soluble complexes (P less than 0.001). These data establish that the true CR1 levels are determined using the microtiter plate ELISA for quantitation of CR1 in patients with diseases involving immune complexes and/or autoantibodies.
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PMID:Erythrocyte CR1 determination using monoclonal antibody in a microtiter plate ELISA; receptors are not masked by immune complexes. 294 11

Polymorphonuclear leukocytes (PMN) C3b receptor (CR1) numbers have been measured in 14 normal individuals and 15 patients with SLE. The results in the normals showed that PMN possess three distinct pools of CR1. CR1 expression was lowest at 0 degrees C (mean 86,000 +/- s.e.m. 7,000), but increased when the cells were incubated at 37 degrees C (125,000 +/- 16,000) or when the cells were exposed to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-5) mol 1) at 37 degrees C (207,000 +/- 21,000). The increased expression at 37 degrees C was not dependent upon protein synthesis, an intact cytoskeleton or energy. Although the response to FMLP did not require de novo protein synthesis, increased CR1 expression was dependent upon an intact cytoskeleton and energy. All three PMN CR1 pools were reduced in patients with active SLE, but were normal in those in whom the disease was inactive. Serial studies performed on three SLE patients showed that PMN CR1 numbers were low during periods of disease activity and increased during remission. These data suggest that low PMN CR1 numbers in SLE are a consequence of the disease.
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PMID:C3b receptor (CR1) expression on the polymorphonuclear leukocytes from patients with systemic lupus erythematosus. 295 69

Family studies were carried out to look at CR1 expression in 24 hydralazine-induced SLE patients (Hz Reactors), who had been off the drug for at least 1 year and were clinically well at the time of the study. Mean expression of CR1 was reduced by 27% in the group of hypertensives who had developed Hz-induced SLE compared with a group of 35 normal individuals. CR1 expression was also slightly reduced in the relatives of the Hz Reactors compared to the normal group. Using a solid-phase Clq binding assay, CIC levels were found to be elevated in the plasma of the Hz reactors and an inverse relationship was found between CR1 levels and CIC levels in this patient group. Both CR1 levels and CIC levels in Hz Reactors and normal individuals were constant over the 36 weeks studied. This study suggests that there is an association between an inability to deal efficiently with CIC and susceptibility to developing Hz-induced SLE.
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PMID:Erythrocyte complement receptor type 1 (CR1) expression and circulating immune complex (CIC) levels in hydralazine-induced SLE. 295 87

One hundred and sixty-two unrelated, healthy normals and 118 unrelated SLE patients were subdivided by sex, race, and disease, and each group was in Hardy-Weinberg equilibrium for autosomal codominant expression of the four CR1 alleles. There were no significant phenotypic differences between males and females (P greater than 0.3) or between normals and SLE patients (P greater than 0.2). However, gene frequencies among whites (A:0.87; B:0.12; C:0; D:0.01), blacks (A:0.74; B:0.22; C:0.04; D:0) and orientals (A:0.98; B:0.02; C:0; D:0) were significantly different (P less than 0.05). We had previously reported that SLE patients of phenotype AC had higher relative expression of the C allele than normals and this was confirmed: 61% (SLE, n = 5) vs 22% (normals, n = 3; P = 0.014). Total CR1/E in the AC group (193 in SLE vs 393 in normals 0.05 less than P less than 0.10), was suggestive of the decreased CR1 number seen in larger SLE populations regardless of phenotype. In one large three-generation family with SLE and the C allele, an association between SLE and the C allele is suggested by the presence of the C allele in all three females with SLE versus 3 of 13 healthy females. In informative families in which receptor phenotype and CR1 number/E were determined, it was possible to assign a receptor number to an allele. These data provide evidence for a cis-acting regulatory element that is inherited in association with the CR1 structural gene.
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PMID:The polymorphism of the C3b/C4b receptor in the normal population and in patients with systemic lupus erythematosus. 295 90

It has long been the conventional wisdom that most autoimmune responses represent a pathological aberration of the immune system and a great deal of effort has been devoted to investigating how such abnormal responses may be induced. It seems likely, however, particularly in the form of autoimmunity seen in diseases like systemic lupus erythematosus (LE) and associated with immune complex disease, that it is not the induction of the autoimmune response that is primarily abnormal, but its persistence, and that this abnormal persistence is a consequence of a failure of the proper functioning of the effector mechanisms of the immune response. The strongest reason for so believing is the striking incidence of these diseases in subjects with deficiencies of the early components of the classical complement pathway. Total, homozygous deficiencies are rare and account for only a small proportion of patients with systemic LE. However, partial, heterozygous deficiency of these components is much commoner and also carries an increased susceptibility to these diseases. An explanation for this association is given. In the presence of an adequately functioning complement system immune complexes remain soluble and of relatively small size. It is proposed that this is a result of the incorporation of C4 and C3 into the antigen-antibody lattice leading to a reduction in the effective valency of antigen and antibody. The Goldberg theory of immune precipitation predicts that a reduction in valency would inhibit precipitation and the formation of large complexes. In the absence of adequate complement function this mechanism will fail and large, potentially insoluble complexes with little C4 and C3 on them will be formed. These large immune complexes without sufficient C4 and C3 bound on them will also not be bound normally to erythrocyte CR1 and will therefore be transported in the (peripheral) plasma stream rather than in the (central) erythrocyte stream. It is proposed that this will result in the deposition of immune complexes in peripheral small blood vessels rather than in the sinusoids of the liver and spleen; and that this peripheral deposition gives rise to inflammation, with the release of autoantigens and the formation of further autoantibodies. The importance of CR1 in relation to these diseases is emphasized by the reduction in CR1 numbers that accompanies their active phase. This appears to be due to proteolysis of the receptor while the immune complex-bearing erythrocyte is sequestered in the reticuloendothelial system.
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PMID:Deficiency of the effector mechanisms of the immune response and autoimmunity. 296 May 1

Fifty-four patients with systemic lupus erythematosus (SLE) were examined for (1) CR1 (C3b/C4b receptor) levels on erythrocytes by an enzyme-linked immunosorbent assay, (2) levels of circulating immune complexes (IC) by a polyethylene glycol precipitation complement consumption method, and (3) concentrations of C3d split products in plasma by intermediate gel rocket immunoelectrophoresis. A preponderance of low CR1 levels was found among patients with SLE (mean 40%, range 13-106) as compared with normal controls (mean 70%, range 24-130) (p less than 0.001). The concentrations of circulating IC were elevated in 38% of 58 samples. The concentrations of C3d were elevated in 72%, and were positively correlated with the levels of IC (tau = 0.28; p less than 0.005) and with disease activity as assessed by a modification of the UCH/Middlesex criteria. Negative correlations were seen between the CR1 numbers and disease activity (p = 0.01), concentrations of circulating IC (tau = -0.14; p less than 0.005), and C3d (tau = -0.21; p less than 0.005). The changes found in CR1 levels on repeated study were, however, relatively small (less than or equal to 27%; median 5), even during periods of changing disease activity.
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PMID:Erythrocyte CR1 (C3b/C4b receptor) levels and disease activity in patients with SLE. 296 Oct 56

The role of complement and its receptor on erythrocytes (CR1) in the physiologic elimination of large immune complexes from the circulation of humans was assessed. Large radiolabeled soluble tetanus toxoid- anti-tetanus toxoid complexes were injected i.v. into three normal individuals and three patients with SLE. These complexes were prepared in antibody excess and were 45S in size, fixed C and bound to E CR1 in vitro. The percentage of complexes bound in vitro was directly proportional to CR1 number/E in four normal subjects and three SLE patients. After i.v. injection into normal subjects, complexes were cleared rapidly, with a monoexponential rate constant (10.3 to 11% complexes cleared/min). In the SLE patients, clearance was best explained by two phases: the first occurred within the first minute indicating immediate trapping of a fraction of the complexes (19.5 to 25.3% of injected complexes trapped), the second was monoexponential and was similar to the normal range. A large fraction of complexes bound within the first minute to E in vivo; the percentage of binding was variable, ranging from 16.3% to 71.5% and was related to E CR1 number. In a second study complexes were injected that had been attached to autologous E by opsonization with C in vitro. Their elimination was similarly monoexponential, except in one SLE patient in whom there was significant initial trapping (30.9%). A fraction of these complexes were released from E within the first minute, the percentage release being greatest in the patient with the lowest CR1 number (81.4%). E bearing immune complexes remained in the circulation and were not transiently sequestered in the liver or spleen. This is the first study of the clearance of soluble immune complexes in vivo in humans and shows that C and CR1 on E participate in immune complex clearance reactions, and that abnormal clearance can be detected in the form of rapid removal of immune complexes from the circulation.
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PMID:The clearance of tetanus toxoid/anti-tetanus toxoid immune complexes from the circulation of humans. Complement- and erythrocyte complement receptor 1-dependent mechanisms. 296 69


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