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)

C receptor type 1 (CR1, CD35) is present in a soluble form in plasma (sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum concentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and was identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p < 0.0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p < 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/- 24.0 ng/ml (p < 0.001) in nine patients who underwent liver transplantation, and was 33.5 +/- 7.3 in 10 patients with functioning renal grafts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (> 47 ng/ml), which included B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and chronic myeloproliferative syndromes (4/5). By contrast, no increase was observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 decreased rapidly after chemotherapy. The mean concentration of sCR1 was not significantly modified in 181 HIV-infected patients at various stages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with active SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p < 0.0001, and r = 0.60, p < 0.03 respectively). In vitro, monocytes, lymphocytes, and neutrophils were found to release sCR1 into culture supernatants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCR1 levels correlated with those of human IgG (r = 0.97, p < 0.0001), suggesting synthesis of sCR1 by the transferred lymphocytes. The mechanisms underlining the increased levels of sCR1 and its biologic consequences remain to be defined.
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PMID:Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes. 833 53

We have examined the effects of hereditary homozygous C2 deficiency on the processing of radiolabeled soluble immune complexes (IC). A patient with C2 deficiency was studied before and after treatment with fresh frozen plasma (FFP). Hepatitis B surface Ag (HBsAg):anti-HBsAg immune complexes were prepared in vitro using Ag radiolabeled with 123I, and injected intravenously. Dynamic and static gamma-scintigraphy was performed to delineate the sites and kinetics of complex clearance. The patient was initially studied when her C2 level and CH50 were zero, and again 1 wk later after treatment with 12 units of FFP, which normalized these parameters. Before treatment there was rapid uptake of complexes by the liver (t90% [time for 90% uptake] = 13.6 min) and rapid clearance from the circulation (t1/2 = 6.8 min). No splenic uptake was detected, and there was no binding of complexes to erythrocyte CR1. Between 30 and 60 min there was release of 11% of the tracer from the liver. In the second study, performed after normalization of classical pathway complement activity, the t1/2 of IC clearance increased to 9.8 min, and t90% was 27 min. Twenty percent of injected complexes now localized to the spleen, and there was no longer any release of complexes between 30 and 60 min. The kinetics of IC processing and the sites of uptake in this posttherapy study were closely similar to two normal subjects studied in parallel, with a maximum of 72% of injected complexes binding to erythrocytes. These observations indicate that the uptake of immune complexes in the spleen in humans is complement-dependent, and suggest that the observed predisposition to SLE in patients with complement deficiency may be related to abnormal processing of immune complexes.
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PMID:Splenic uptake of immune complexes in man is complement-dependent. 837 7

Primate erythrocytes express complement receptors (E-CR), which can extrinsically bind C3b and Cb4. This interaction allows primate erythrocytes to bind complement opsonized particles and immune complexes, a phenomenon historically referred to as immune adherence. The binding of C3b and C4b by E-CR also leads to inhibition of complement activation. The human E-Cr is the complement activation. The human E-CR is the complement receptor type 1, or CR1, which is codominantly expressed as four polymorphic allotypes, ranging in size from 190,000 to 280,000 M(r). Non-human primate E-CR are similar to CR1 in function and antigenicity and are likely homologous to CR1 in structure; however, they are one third to one half the size of CR1. The physiological role of E-CR, determined from studies in monkeys and humans, is to allow erythrocytes to perform as inert shuttles for circulating immune complexes (IC), safely directing IC to the organs of the monocyte phagocytic system, thus preventing indiscriminate IC deposition in vulnerable tissue. In IC-mediated diseases, such as systemic lupus erythematosus (SLE), detectable erythrocyte CR1 levels are reduced, an abnormality that in part is acquired during disease activity. The loss of erythrocyte CR1 may be an important pathogenic factor in the development and severity of SLE.
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PMID:Erythrocyte complement receptors. 857 85

We have prepared cross-linked, bispecific complexes [heteropolymers (HP) and antigen-based heteropolymers (AHP)] that facilitate complement-independent binding of target model pathogens or autoantibodies to primate erythrocytes (E) via complement receptors (CR1). The method is based on using monoclonal antibodies (mAb) specific for CR1 that either are cross-linked to an mAb specific for a prototype pathogen (e.g., IgE) or are cross-linked to an autoantigen (e.g., dsDNA) that is recognized by circulating pathogenic autoantibodies in the autoimmune disease systemic lupus erythematosus (SLE). The underlying assumption in this research is that complexed ligands containing IgG bound to primate E CR1 should be recognized and processed via the same mechanism by which complement-opsonized immune complexes bound to E CR1 are cleared from the circulation and phagocytosed in the liver and spleen. Our work in experimental monkey models has demonstrated that binding of substrates to primate E via this method does indeed lead to the safe and rapid clearance of the target pathogens or autoantibodies from the circulation, without any lysis or loss of the E. Although a number of questions must still be resolved, it may be possible to generalize these findings and use this CR1-based approach to develop a simple noninvasive bispecific therapy that can be used to clear pathogens or autoantibodies from the circulation.
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PMID:Primate erythrocyte (E) complement receptor (CR1) as an anchor site for bispecific-based therapies to clear pathogens or autoantibodies safely from the circulation. 858 69

Expression of the human erythrocyte C3b receptor (CR1-CD35) and its Hind III RFLP was studied in a group of 37 patients with SLE, 15 consanguineous relatives of the patients and 48 healthy normal subjects. The CR1 number on erythrocytes was quantitated by ELISA using a mAb to CR1. Serum levels of complement proteins (C3, C4, C3d) and circulating immune complexes (CIC) were estimated simultaneously in controls and relatives. The patients were followed up during the course of the treatment. The CR1/erythrocyte (CR1/E) in patients were found to be significantly low in comparison to controls. The gene frequencies for the alleles H and L (7.4 and 6.9 kb Hind III restriction fragments) in the patients were 0.75 and 0.25, respectively, which did not differ significantly from the controls (0.77 and 0.23 in normal subjects and 0.79 and 0.21 in consanguineous relatives of the patients). However, patients expressed fewer CR1/E within each genotype than their relatives and healthy subjects. CR/E was found to be stable in consecutive samples in controls. In patients, the numbers varied between low and high during the course of the treatment. The variation in the numbers was significantly correlated with C3d and CIC as well as with the severity of the disease. Our results suggest that low levels of CR1 on erythrocytes in SLE patients are required during the course of the disease and that the 6.9 kb restriction fragment does not play a role in causing susceptibility to the disease.
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PMID:Hind III genomic polymorphism of the C3b receptor (CR1) in patients with SLE: low erythrocyte CR1 expression is an acquired phenomenon. 859 25

CR1 exhibits a molecular weight polymorphism and variability in the number of C3b-binding sites. Because this may affect immune complex clearance, we used erythrocytes to investigate the CR1 size polymorphism in SLE patients from three ethnic groups. The CR1-C allele was found more frequently in African-Americans, but the frequency did not differ between controls (10%, n = 63) and SLE patients (9%, n = 79). A 160-kD band similar to CR1-C was noted in a number of patients and was shown to be a proteolytic cleavage fragment. The study shows that the smallest form of CR1, i.e. CR1-C, is not a genetic risk factor for SLE and that the frequencies of the CR1 structural alleles do not differ from race-matched healthy controls.
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PMID:Structural polymorphisms of complement receptor 1 (CR1) in systemic lupus erythematosus (SLE) patients and normal controls of three ethnic groups. 870 38

The number of CR1 on podocytes is reduced in nephropathies with severe glomerular damage, especially in the diffuse proliferative glomerulonephritis (DPGN) of systemic lupus erythematosus (SLE). Reduction of CR1 number on erythrocytes is due to proteolysis of CR1 by macrophage proteases activated by the reaction of their complement receptors, which leaves a 'CR1 stump peptide' on the erythrocyte. In the present study, we demonstrated the presence of the terminal complement complex (TCC) and the CR1 stump in histological sections of biopsies from patients with SLE by the indirect immunoperoxidase technique. Less severe glomerular lesions presented TCC deposits mainly in the mesangium (mesangial pattern). In lupus nephritis, with more severe glomerular damage, TCC deposits were detected both in the mesangium and in the capillary loops with podocyte involvement (mixed pattern). Patients with highly active DPGN presented a marked reduction of intact podocyte CR1 receptors in association with increased reactivity to the anti-CR1 stump antibody and with glomerular TCC deposits of mixed histological pattern. These results suggest that the decrease in the number of podocyte CR1 receptors in severe glomerular lesions of SLE may be due to a local proteolytic activity associated with activation and deposition of TCC.
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PMID:CR1 stump peptide and terminal complement complexes are found in the glomeruli of lupus nephritis patients. 880 40

The present study investigated the expressed number of CR1 on erythrocytes (E) in relationship of the CR1 density genotype from 46 patients with systemic lupus erythematosus (SLE) and 47 healthy volunteers. The CR1 genotype was determined by a method based on polymerase chain reaction (PCR) amplification of the genomic DNA fragment of 1.8 kb separated by HindIII endonuclease digestion and agarose gel electrophoresis. Our data supported the earlier results that the number of binding sites/E for monoclonal anti-CR1 decreased among SLE patients compared with normal individuals having the same alleles for the CR1/E density. At the same time the novelty of our recent results was that the decreased expression of CR1 on E correlated significantly with kidney involvement in patients homozygous for the CR1/E high density allele (HH). These data suggest that the deficiency of the detectable number of CR1 on erythrocytes is acquired in this SLE population.
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PMID:CR1 density polymorphism and expression on erythrocytes of patients with systemic lupus erythematosus. 916

Human complement receptors type 1 (hCR1;CD35) and type 2 (hCR2;CD21) are expressed on B lymphocytes at specific stages during differentiation and activation. These receptors play critical roles in the immune response to T-dependent Ags in addition to germinal center formation. Expression of both hCR2 and hCR1 is decreased on B lymphocytes of patients with systemic lupus erythematosus (SLE). We have studied the expression of mouse CR2 and CR1 on normal populations of mouse B lymphocytes in BALB/c mice. Our results demonstrate that expression of these receptors in the normal state closely parallels that of hCR2. During bone marrow development, expression is first detected on low B220/high IgM cells, demonstrating that complement receptors appear after central tolerance mechanisms are completed. In the splenic microenvironment the highest levels of receptor expression are found on marginal zone B lymphocytes. Mouse CR2 and CR1 are also found on peritoneal B1a and B1b cells in addition to IgA+ Peyer's patch B cells. Activation of splenic B cells under Th2 conditions results in a marked decrease in receptor expression. To determine whether the patterns of receptor expression also parallel those found in human disease, we studied the MRL lpr/lpr (MRL/lpr) model of SLE. Interestingly, we found an early decrease in complement receptor expression that is progressive and first detectable before major clinical manifestations of nephritis. We hypothesize that the early decrease in complement receptor expression such as that demonstrated by MRL/lpr mice plays an important role in the pathogenesis of murine and perhaps human SLE.
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PMID:Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice. 923 55

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


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