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 and CR1 have been shown to participate in the clearance of injected, preformed, immune complexes in humans and in non-human primates. Their role in the physiologic disposal of immune complexes formed in vivo in humans was investigated in three patients receiving radioimmunotherapy for ovarian carcinoma. On day 0 each patient received, by intraperitoneal injection, 10 mg of 131I-mouse anti-tumor mAb (10 mCi/mg). On days 1 and 2, 18 mg of trace-labeled, 125I-human anti-mouse IgG was administered by i.v. infusion over 15 min, to accelerate the clearance of the 131I-anti-tumor antibody from the circulation and reduce the radiation dose to the marrow. Sequential blood samples were obtained after the injection of the second (anti-mouse) antibody, to monitor clearance. Immune complexes (shown by sucrose gradient centrifugation to be 19 to 40 S in size) formed within 5 min, and were cleared with a half-life of 11 +/- 1.7 min in the liver. Complexes were measured by 4% polyethylene glycol precipitation, and by solid phase C3d- and C1q-binding assays. Between 8 and 11% of the total available complexed material bound to CR1 on E. Peak binding of immune complexes to red cells occurred 10 min after the maximal complex load was detected by precipitation with polyethylene glycol. At that time, immune complexes bound to E constituted one-fifth of the total circulating pool of complexes. Coincident with immune complex formation and clearance, a 47% fall in serum C4, C3, and CH50 was measured, with the deposition of up to 1230 molecules of C4, and 2590 molecules of C3 on the surface of red cells. During 20 min after immune complex formation there was a mean loss of 32% of erythrocyte CR1. The changes in complement and CR1 on E and in serum observed in these patients resembled those seen in patients with SLE: i.e., a reduction in CR1 and an increase in C3 and C4 on E, and reduced serum C.
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PMID:A study of in vivo immune complex formation and clearance in man. 214 Oct 40

The human C3b receptor (CR1) is a polymorphic glycoprotein which functions regulating the complement system by inhibiting the activation of C3 and C5, through its effect on their convertases, and serving as cofactor for factor I in mediating the degradation of C3b to its inactive fragment C3bi and further to C3d-g. The latter are then ligands for their respective receptors on leukocytes, CR3 and CR2. Additionally, CR1 on erythrocytes endows these cells with the capacity to deliver immune complexes (IC) to the reticuloendothelial system, resulting in their clearance from the circulation. On phagocytes, this receptor participates in the process of endocytosis of foreign particles. There is a wide inherited variation of CR1 expression on erythrocytes (CR1/E) of different individuals. Patients with diseases which feature elevated levels of IC, such as systemic lupus erythematosus, leprosy, and AIDS, have a marked decrease of CR1/E, which may result in an altered clearance. This reduction appears to be related to disease activity, and the most probable site for CR1/E loss is during the transfer of IC to macrophages. Healthy neutrophils increase tenfold their expression of CR1 in response to the effect of chemoattractant peptides. Neutrophils from patients with AIDS display an altered response to stimulation. This defect may be of relevance in the process of endocytosis.
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PMID:The human C3b receptor: function and role in human diseases. 214 Oct 47

Erythrocytes (E) from a cross-sectional group of 22 outpatients with systemic lupus erythematosus (SLE) and/or mixed connective tissue disease (MCTD), the majority without active disease (n = 14), were analyzed for CR1 antigen expression and capacity to bind complement opsonized, radiolabelled immune complexes (IC). Furthermore, E-bound C3 fragments and the plasma C3d concentration were determined. E-bound C3b/iC3b fragments were not elevated in patients with SLE, whereas E from 11 out of 22 SLE patients had increased C3d levels which correlated with the plasma C3d concentration (Rs 0.73, p less than 0.001). E-fixed C3d fragments did not affect the binding of Mab or preopsonized IC to E-CR1 and were not correlated with disease activity or medical treatment. Antigen expression of E-CR1 measured by ELISA or agglutination showed positive correlation with the IC binding capacity of E-CR1 (Rs 0.92 and 0.72 respectively, p less than 001). The IC binding capacity of E-CR1 from SLE patients was significantly reduced (p less than 0.005), whereas the antigen expression of CR1 (ELISA) on E from the patients did not differ from that of E from healthy donors (p greater than 0.1). E-CR1 antigen was measured by Mab reacting with an epitope outside the IC-binding site of E-CR1. E-CR1 antigen expression or IC binding showed no correlation either with disease activity or prednisolone treatment. However, 4 og 5 patients with MCTD and 4 of 5 patients receiving Imurel were found to have low E-CR1 expression and capacity to bind IC. Thus, measurement of antigenic E-CR1 in a cross-sectional group of SLE outpatients by use of Mab reacting with an epitope outside the ligand-binding region of CR1 did not reveal a significantly reduced CR1 expression. However, an assay for CR1-mediated IC binding showed a clearly reduced E-CR1 function.
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PMID:Immune complex binding to erythrocyte-CR1 (CD 35), CR1 expression and levels of erythrocyte-fixed C3 fragments in SLE outpatients. 214 31

The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 alpha and beta chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-convertase function by 50-100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3 alpha chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CR1 (CD35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CR1. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mediated functions.
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PMID:Purification and characterization of IgG immunoconglutinins from patients with systemic lupus erythematosus: implications for a regulatory function. 214 95

Erythrocytes from 42 systemic lupus erythematosus (SLE) patients and 80 healthy volunteers were tested for the immunoadherence (CR1) receptor reactivity, observed by hemagglutination (IAHA) when incubating erythrocytes and aggregated human gamma-globulin (AHGG)-complement in appropriate proportions. Reactivity was expressed as the highest two-fold dilution of AHGG (2n) that induced hemagglutination. Erythrocytes of 15 SLE patients (35.7%) showed reactivity compared with 70 normal controls (87.5%). Both groups showed a trimodal distribution of IAHA titers in accordance with the three phenotypic groups described by other authors. Of the healthy population 72.5% belong to the intermediate reactivity mode (2(6) to 2(8)) and 64.3% of the SLE patients to the low reactivity group (negative). There was no correlation between CR1 defective expression and conventional activity parameters. This erythrocyte receptor involved in the immunocomplex clearance process, which constitutes 95% of the circulating CR1, is another factor that contributes to the pathophysiology of the disease when it is defective.
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PMID:[Erythrocyte CR1 receptor reactivity in patients with systemic lupus erythematosus]. 214 69

CR1 (CD35) and CR2 (CD21) are structurally related integral transmembrane glycoproteins that function as cellular receptors for human C3b and C3dg, respectively. The primary sequence of the most common structural allotype of CR1 and that of CR2 have been established, and ligand binding on the molecules has been mapped. CR1 and CR2 genes are located in close vicinity in the RCA locus of chromosome 1. CR1 has a wide cellular/tissular distribution and mediates a variety of biologic functions, including the transport of C3-bearing immune complexes on erythrocytes, enhancement of phagocytosis, induction of IL-1 secretion and enhancement of B-cell differentiation. Expression of CR2 is restricted to B lymphocytes and follicular dendritic cells. The receptor modulates B-cell growth. CR2 also serves as the receptor for EBV and determines the cellular tropism of the virus. This review discusses the molecular biology and functional characteristics of CR1 and CR2. It focuses on alterations of expression of the receptors in disease, with particular emphasis on the genetic and acquired factors that contribute to the defective expression of CR1 in patients with systemic lupus erythematosus.
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PMID:Deficiencies of human C3 complement receptors type 1 (CR1, CD35) and type 2 (CR2, CD21). 216 22

The human complement system is comprised of 19 plasma components and regulatory proteins and of at least 9 distinct cellular receptors for these proteins or their activation fragments. The important role of complement in host defense against infection is related to its capacity to opsonize microorganisms, lyze target cells, and induce the release of inflammatory mediators from leukocytes. Complement participates in the processing and clearance of immune complexes and in regulation of the immune response. Most of the biologic effects derived from complement activation depend on ligand-receptor interactions between complement proteins or their cleavage fragments and specific receptors on cells. Two types of ligands are generated during complement activation: soluble low-molecular-weight ligands, such as the anaphylatoxins C3a and C5a, and so-called bifunctional ligands that attach both to the target of complement activation (opsonins) and to the appropriate receptor on effector cells. The most abundant complement protein in plasma is C3. Activation of the classic and alternative complement pathways generates C3 convertases that cleave C3 into an anaphylatoxic fragment, C3a, and a major fragment, C3b, which is capable of forming a covalent linkage with the targets of complement activation. Surface-bound C3b is the preferential ligand for the C3b receptor, CR1 (CD 35), which is expressed on most peripheral blood cells. The receptor plays an important role in the processing of immune complexes, the phagocytosis of C3b-bearing microorganisms, and regulation of the immune response. The cellular expression of the molecule is decreased in patients with systemic lupus erythematosus (SLE) and in patients infected with the human immunodeficiency virus (HIV).
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PMID:The human C3b receptor (CR1). 252 67

Defective clearance of immune complexes (IC) may contribute to the pathogenesis of diseases such as SLE. We studied the effect of hypocomplementaemia and the influence of erythrocyte complement receptor type 1 (CR1, CD35) number on the clearance of radiolabelled tetanus toxoid (TT)-anti-TT IC from the circulation. These were injected intravenously into 9 normal subjects and 15 patients with diseases characterized by IC formation and/or hypocomplementemia, including 2 with hereditary complement deficiency. IC were found to bind to erythrocyte CR1 in a complement-dependent manner and their degree of uptake was directly correlated with CR1 numbers. Two phases of IC clearance were identified. The first was rapid, occurring within 1 min. Since this phase might represent inappropriate deposition of IC in target organs we called it trapping. It was seen predominantly in subjects with low CR1, low complement, and low binding of complexes to red cells. The second phase was monoexponential with a mean elimination rate of 14.1%/min; it was inversely correlated with CR1 numbers and binding of complexes to red cells. In a second study each individual was injected with IC bound to autologous erythrocytes in vitro using normal serum so that the effects of complement deficiency were eliminated. Up to 81.4% of these bound IC were released in vivo from erythrocytes in 1 min, and the proportion was inversely correlated with CR1 numbers. Only five patients showed trapping, and these had low CR1 numbers and high percentage release of IC. The second phase of elimination was inversely correlated with CR1 numbers and the proportion of IC remaining bound to red cells at 1 min. The two complement-deficient patients had normal CR1: when IC were injected, trapping and very fast clearance rates were observed; however complexes that had been opsonized and bound to erythrocytes were cleared at a slower rate without evidence for trapping. These studies show that complement and erythrocyte CR1 may determine the physiological clearance of certain types of IC and suggest that this system may function abnormally when CR1 number or complement function are reduced.
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PMID:The role of hypocomplementaemia and low erythrocyte complement receptor type 1 numbers in determining abnormal immune complex clearance in humans. 252 42

Using a novel technique previously described for measuring erythrocyte C3b receptors (E-CR1) by means of flow cytometry, we studied E-CR1 levels in patients with various diseases. We also measured C3b receptors of B cells (B-CR1) by flow cytometry, and studied the correlation between E-CR1 levels and B-CR1 levels. We have found; 1) Decreased E-CR1 levels were seen in patients with active SLE, acute leukemia, and congenital immunodeficiency syndrome. E-CR1 levels in patients with IgA nephropathy, membranoproliferative glomerulonephritis, anaphylactoid purpura, infectious mononucleosis, and viral pneumonia were statistically higher than those in normal controls. 2) Decreased E-CR1 levels in some patients with SLE were not thought to be inherited, but the E-CR1 levels of patients with diseases other than SLE appeared to be regulated in an autosomal co-dominant form of inheritance. 3) A negative correlation was observed between E-CR1 levels and B-CR1 levels in both patients with SLE and normal controls.
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PMID:[Flow cytometric measurement of C3b receptors (CR1) on human erythrocytes. II. E-CR1 levels in patients with various diseases and their correlation with B-CR1]. 253 36

The role of genetic factors in decreased expression of CR1 in patients with systemic lupus erythematosus (SLE) was investigated by assessing the frequency of genotypes determining the numbers of CR1 on erythrocytes obtained from 52 patients with SLE and from 84 normal individuals. The expression of CR1 was quantitated using flow cytometry. Genotypes were determined by analyzing the CR1 gene restriction fragment length polymorphism using the CR1.1 complementary DNA probe and the Hind III restriction enzyme. In normal subjects, the distribution of the HH, HL, and LL genotypes fit the Hardy-Weinberg law. The frequency for the H allele did not differ between the 2 groups. No individual homozygous for the LL genotypes was found among the SLE patient population. Taken together, data from this and previous studies indicate an under-representation of the LL homozygous genotype in patients with SLE. SLE patients expressed decreased numbers of CR1 per erythrocyte within each genotype compared with these numbers in normal subjects. The results suggest that defective expression of CR1 in SLE patients is acquired and that the presence of the L allele is not linked to a genetic susceptibility for SLE.
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PMID:Genetic analysis of CR1 expression on erythrocytes of patients with systemic lupus erythematosus. 256 13


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