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)

In the course of examining the structure and function of Fc receptors on peripheral blood cells of patients with systemic lupus erythematosus, we identified a patient whose neutrophils did not react with either monoclonal or polyclonal antibodies to Fc receptor III. However, neutrophils from the patient were comparable to neutrophils from healthy controls with respect to their expression of Fc receptor II, complement receptor 1, complement receptor 3, and the phosphatidylinositol-linked, complement regulatory protein, decay-accelerating factor. The abnormality of expression of Fc receptor III was limited to the patient's neutrophils (her natural killer cells reacted normally with anti-Fc receptor III antibodies), and was associated with abnormal recognition and binding of IgG-coated erythrocytes. Analysis of genomic DNA revealed evidence that failure of the patient's neutrophils to express Fc receptor III was most likely due to an abnormality of the gene that encodes this receptor.
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PMID:An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus. 169 67

C3b-coated immune complexes adhere to the complement receptor 1 (CR1, CD35) on human erythrocytes. This multi-valent binding might be favoured by the known clustering of CR1 and by the multiple C3b-binding sites on each CR1. The size of the CR1 clusters correlates directly with the number of CR1/erythrocytes, and the different structural CR1 alleles bear between two and five C3b-binding sites. Using radiolabelled hepatitis B surface antigen-antibody complexes, we investigated whether CR1 numbers and structural alleles modulate the ability of erythrocytes to bind immune complexes, and assessed if any reorganization of immune complexes takes place at the erythrocyte surface after the initial binding reaction. The binding efficiency (immune complexes/CR1) correlated with CR1 number as determined by the maximal binding at 4 degrees C, the kinetics of binding at 37 degrees C, and the binding in the presence of excess immune complexes and of immune complexes of small size. Binding efficiencies were similar for erythrocytes with low CR1 from normal subjects and patients with AIDS or SLE. A monoclonal antibody blocking the C3b-binding sites (3D9) of CR1 interfered with binding efficiency at a lower concentration on cells bearing low CR1 numbers, suggesting that CR1 clustering is essential. The larger alleles of CR1 (DD and BB) were more efficient than AA alleles. The distribution of immune complexes, visualized by immunofluorescence, was heterogeneous on erythrocytes: about two out of three cells bore between one and 12 immune complexes. No visible immune complex reorganization took place after initial binding, as prefixed erythrocytes displayed the same immune complex distribution and number/erythrocytes as unfixed erythrocytes. The contribution of CR1 alleles in immune complex binding efficiency was confirmed by morphological analysis. These results demonstrate that immune adherence efficiency is the resultant of the CR1 clustering, as well as the particular alleles carried by erythrocytes. Moreover, there is little or no immune complexes surface reorganization after the initial binding reaction.
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PMID:Immune complex binding efficiency of erythrocyte complement receptor 1 (CR1). 182 50

Complement levels and complement receptor 1 (CR1) on erythrocytes (E) are reduced in systemic lupus erythematosus (SLE). To see whether these abnormalities are responsible for defective transport and elimination of immune complexes (IC) from the circulation, patients with active SLE (14) and normal volunteers (14) were injected with preformed IC (hepatitis B surface Ag/Ab). Two minutes after injection only 25.9 +/- 19.1% (mean +/- 1 s.d.) of the circulating IC were bound to E in the SLE patients as compared to 63 +/- 3.7% in the normal subjects (P = 0.0001). For SLE patients, the reduced immune adherence was best explained by a combination of complement depletion and low CR1 binding capacity (tau = 0.80, P = 0.0001). The disappearance of IC as estimated from the area under the elimination curve was faster in SLE than in controls (P = 0.02), and correlated with CR1 (tau = 0.54, P = 0.0001) and immune adherence observed in vivo (tau = 0.33, P = 0.013). Finally, immune adherence was absent and IC disappeared very rapidly in a patient with C2 deficiency and an SLE-like disease. These observations suggest that in SLE the defective immune adherence reaction might be responsible for the accelerated disappearance of IC from the circulation.
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PMID:Immune adherence and clearance of hepatitis B surface Ag/Ab complexes is abnormal in patients with systemic lupus erythematosus (SLE). 189 16

We have developed an ELISA technique to examine RBC-bound molecules in autoimmune disorders. In particular, the technique has enabled us to investigate the role of some complement regulatory proteins in immune complex transport and to suggest that decay accelerating factor (DAF) may be involved in this process. In both autoimmune haemolytic anaemia (AHA) and systemic lupus erythematosus (SLE) a sub-set of individuals was identified, on the basis of patterns of complement receptor 1 (CR1) expression on RBC. In these patients, CR1 identified using the monoclonal antibody E11 was low or absent whereas CR1 identified using a DAKO monoclonal antibody (C3RTo5) was present at normal levels.
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PMID:An enzyme-linked immunosorbent assay for complement regulatory proteins and membrane-bound immunoglobulins on intact red blood cells. 752 8

The erythrocyte complement receptor 1 (ECR1)-immune complex binding assay is a sensitive method for the determination of complement fragments which can be activated by bovine serum albumin (BSA)-anti-BSA in vitro. When the C3b/C4b containing bovine serum albumin (BSA)-anti-BSA was formed in the presence of the serum of patients with systemic lupus erythematosus (SLE) its binding to ECR1 was found to be lower than that formed in sera of normal volunteers. The plasmapheresis of SLE patients homozygous for the CR1/E high density allele displays a beneficial effect on the formation of C3b/C4b containing BSA-anti-BSA and its binding to ECR1. There was no significant correlation between the serum C3/C4 level and the percentage of C3b/C4b containing BSA-anti-BSA binding to the ECR1 of SLE patients during plasmapheresis. At the same time, there was an inverse correlation between the serum immune complex level and the ECR1 binding, which was significant in 3 of 5 cases. These data suggest that, besides the determination of different components of complement activation, the functional assay of complement activation might be useful in monitoring the effect of plasmapheresis in SLE.
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PMID:Serum complement activation of SLE patients during plasmapheresis. 927 79

A new in vitro method is presented for measuring directly the ability of sera to induce binding of immune complexes (ICs) to erythrocytes (ICRB assay). The assay measures the binding of alkaline phosphatase (AP)-anti-alkaline phosphatase (anti-AP) complexes formed in the presence of the test sera to the complement receptor 1 (CR1) on normal human red blood cells (RBCs). By using a standard serum source, the assay can also be used to measure the IC binding ability of RBCs from different donors. As compared to the traditional CH50 method, the ICRB assay generally showed more pronounced abnormality in 10 individuals tested, of whom 5 had primary deficiency of classical pathway components. Seven out of ten individuals had systemic lupus erythematosus (SLE) and 2/10 had other rheumatic diseases without primary complement deficiency. The ICRB measured in samples from 9 other patients with SLE was significantly decreased when compared to values from 80 normal individuals. ICRB in serum samples from a C2 deficient SLE patient collected during plasma infusion treatment reflected closely the rising amount of C2 in the serum. Using RBCs from different donors ICRB activity correlated well with the numbers of CR1 as measured by a flow cytometric assay (FCA). These methods should be valuable for measuring the overall IC clearance capacity of the blood and have the advantage that the use of radioactive isotopes is avoided.
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PMID:An enzyme based assay for the measurement of complement mediated binding of immune complexes to red blood cells. 961 41

The low levels of complement receptor 1 (CR1) on erythrocytes in autoimmune diseases and AIDS may be due to accelerated loss in the circulation, or to a diminished expression of CR1 on the red cell lineage. Therefore, we analyzed the expression of CR1 on reticulocytes (R) vs erythrocytes (E). Healthy subjects had a significant higher CR1 number per cell on R (919 +/- 99 CR1/cell) than on E (279 +/- 30 CR1/cell, n = 23), which corresponded to a 3. 5- +/- 1.3-fold loss of CR1. This intravascular loss was confirmed by FACS analysis, which showed that all R expressed CR1, whereas a large fraction of E was negative. The systemic lupus erythematosus (SLE), HIV-infected, and cold hemolytic Ab disease (CHAD) patients had a CR1 number on R identical to the healthy subjects, contrasting with a lower CR1 on their E. The data indicated a significantly higher loss of CR1 in the three diseases, i.e., 7.0- +/- 3.8-, 6.1- +/- 2.9-, and 9.6- +/- 5.6-fold, respectively. The intravascular loss was best exemplified in a patient with factor I deficiency whose CR1 dropped from 520 CR1/R to 28 CR1/E, i.e., 18.6-fold loss. In one SLE patient and in the factor I-deficient patient, the FACS data were consistent with a loss of CR1 already on some R. In conclusion, CR1 is lost progressively from normal E during in vivo aging so that old E are almost devoid of CR1. The low CR1 of RBC in autoimmune diseases and HIV-infection is due to a loss occurring in the circulation by an active process that remains to be defined.
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PMID:Complement receptor 1 (CD35) on human reticulocytes: normal expression in systemic lupus erythematosus and HIV-infected patients. 1035 11

This study assessed the expression of complement receptor 1 (CR1), decay accelerating factor (DAF) and membrane inhibitor of reactive lysis (CD59) on the erythrocytes and glomerulus of diffuse proliferative glomerulonephritis (DPGN) of systemic lupus erythematosus (SLE) patients using flow cytometry and immunofluorescence techniques to elucidate their role in the pathogenesis of DPGN. Expression of CR1 on the erythrocytes and glomerulus of DPGN patients was reduced compared with expression in normal subjects. However, expression of DAF and CD59 was increased on both erythrocytes and glomerulus of DPGN patients, suggesting the generation of a protective response against complement-mediated injury.
Lupus 2000
PMID:Expression of complement regulatory proteins in diffuse proliferative glomerulonephritis. 1078 10

A great deal of information has accumulated implicating the complement system in several human disease processes. Although some of this information is circumstantial, protein inhibitors of the complement system have been developed and applied successfully to experimental disease models in animals. Two inhibitors, soluble complement receptor 1 (sCR1) and anti-C5 monoclonal antibody, are now being investigated in a variety of clinical conditions such as systemic lupus erythematosus and rheumatoid arthritis (RA), diseases for which current therapy has changed little and remains unsatisfactory. Preliminary successes in Phase II clinical trials of RA have provided optimism that complement inhibition might prove useful in these diseases and become part of standard medical therapy.
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PMID:Use of complement inhibitors in tissue injury. 1222 14

Experiments in primates have demonstrated that immune complexes (IC) bound to erythrocytes (E) via complement receptor 1 (CR1) are cleared to the liver in a process which removes CR1, but otherwise spares the E. Human E are stabilized for >1 h in the circulation of the mouse if the terminal complement pathway is blocked, and we used this paradigm to examine clearance in a mouse model. Human E were opsonized with an anti-CR1 mAb cross-linked to dsDNA (antigen-based heteropolymer, AHP), and then incubated with systemic lupus erythematosus (SLE) plasmas containing IgG anti-dsDNA to form IC in situ. These IC stably bind to E CR1 in the complete absence of complement, thus allowing analysis in a model which does not require human C3b to facilitate E binding. Dual label experiments, based on RIA, flow cytometry and fluorescence microscopy, were employed to monitor separately E and IC. When opsonized E-IC were injected into A/J mice, >90% of the IC were rapidly removed from the E coincident with loss of CR1. The E remained in the circulation while IC were localized to the liver, mainly to Kupffer cells. Preliminary experiments in NZB/W mice, which spontaneously develop IgG anti-dsDNA, indicated that infusion of E-AHP led to rapid binding of murine IgG to the E-AHP, followed by removal of the nascent IC from E, and loss of CR1 in a concerted reaction. These studies provide additional evidence that E CR1 functions as a privileged site for IC clearance, and that the key step in clearance requires removal of CR1 from E to release bound IC for uptake by acceptor macrophages. This model can be extended to genetically altered mice to investigate the role of specific Fc gamma receptors as well as complement receptors in IC clearance.
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PMID:Concerted clearance of immune complexes bound to the human erythrocyte complement receptor: development of a heterologous mouse model. 1237 24


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