Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1q”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources
PubMed1997

The C1q and collectin binding site within C1q receptor (cell surface calreticulin).

C1q receptor (C1qR/collectin receptor/cC1qR) has an almost complete amino acid sequence identity with calreticulin (CRT). C1qR/CRT is located on the surface of many cell types. Binding of C1q to C1q receptor elicits a range of immunological responses. C1qR also interacts with the collectins SP-A, MBL, CL43 and conglutinin via a cluster of charged residues on the collagen tails of the ligands. In order to localise C1q and collectin binding activity within C1qR/CRT, recombinant C1qR/CRT domains [N (residues 18-196), P (197-308) and C (309-417)] were produced. Both the N- and P-domains bound to C1q, demonstrating that the binding site spans the intersection of these domains. Amino acid alignment analysis identified a putative CUB module within this region. This S-domain (residues 160-283) was expressed and showed concentration-dependent binding to immobilised C1q, demonstrating that it contains the C1q binding site. Competitive inhibition studies of the S-domain-C1q interaction revealed that the S-domain binds to C1q collagen tails and to the collectin proteins, SP-A, MBL, CL43 and conglutinin. The C1q and collection binding site on C1qR/CRT has therefore been localised to the S-domain.

Amino Acid Sequence↗
PubMed1980

Nonparticipation of C1q in the decrease of complement activity in the cold in sera of patients with chronic liver diseases.

Serum and plasma samples taken simultaneously from 560 patients with various diseases were examined for hemolytic complement activity (CH50) after incubation at 4 degrees C for 20 h. Serum CH50 titers less than 20 U/ml were observed in 39 cases and among them, a difference between serum and plasma CH50 of more than 5 U/ml were observed in 16 cases. Diagnosis of most of them were chronic liver diseases. To analyze the dissociation of CH50 titers between serum and plasma, sequential estimations of CH50 were performed on serum and plasma samples which showed the dissocation incubated at 4 and 37 degrees C. Marked decrease in CH50 titers was obtained in sera but not in plasma incubated at 4 degrees C. In such sera, however, no significant decrease of protein amount and agglutinating activity of C1q was observed. The result could indicate that C1q would not participate in the decrease of serum hemolytic activity in the cold, suggesting an activation of complement other than the classical pathway.

Antigen-Antibody Complex↗
PubMed2004

Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice.

C1q deficiency in both humans and mice is strongly associated with autoimmunity. We have previously shown that bone marrow transplantation (BMT) restored C1q levels in C1q-deficient (C1qa(-/-)) mice. Here, we studied the effect of BMT on autoimmunity in C1qa(-/-) mice. Following irradiation, young C1qa(-/-) or wild-type MRL/Mp mice received bone marrow cells (BMC) from strain-matched wild-type or C1qa(-/-) animals. C1q levels increased rapidly when C1qa(-/-) mice received BMC from wild-type mice. Conversely, they decreased slowly in wild-type mice transplanted with C1qa(-/-) BMC. C1qa(-/-) animals transplanted with C1qa(-/-) BMC demonstrated accelerated disease when compared with wild-type mice given wild-type BMC. In contrast, a significant delay in the development of autoantibodies and glomerulonephritis was observed in C1qa(-/-) mice reconstituted with wild-type BMC, and the impaired clearance of apoptotic cells, previously described in C1qa(-/-) mice, was rectified. Moreover, the autoimmune disease was accelerated in wild-type mice given C1qa(-/-) BMC compared to animals transplanted with wild-type cells. These results provide supporting evidence that BMT may be a therapeutic option in the treatment of autoimmunity associated with human C1q deficiency.

Animals↗
PubMed1981

Interaction of collagen with C1q via its collagen-like portion.

Interactions between human collagens type I, II and III with human C1q or its collagen-like fragment (CLF) were investigated with different techniques. It was found that in solution both C1q and CLF form stable complexes with the native collagens. No preferential binding to a specific collagen type was observed. If C1q (CLF) was adsorbed to polystyrene or fixed to erythrocytes, a more efficient interaction with collagen was displayed by C1q than by CLF. If collagen represents the solid phase, the binding of CLF is stronger than that of C1q. Inhibition studies indicate that the interaction between C1q and collagens takes place via the collagen-like part of C1q. Intermolecular attraction due to polar amino acid residues seems to be of major importance for this interaction.

Carrier Proteins↗
PubMed1987

Detection of C1q-bearing immune complexes by a monoclonal anti-C1q ELISA system.

A monoclonal antibody directed against the collagenous portion of human C1q was used to detect C1q-bearing immune complexes in patients with rheumatic disorders. Sera of patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), osteoarthritis, as well as normal human sera (NHS) used as controls were tested in an ELISA system. C1q-bearing immune complexes were bound to a solid-phase monoclonal anti-C1q antibody, and detected with F(ab')2 antibodies to human IgG. Heat-aggregated human IgG was adjusted to the same concentration as the WHO standard for immune complexes and used for the standard curve in NHS. The mean value in NHS was 19.5 micrograms/ml equivalents of aggregated IgG. Using 2 SD over the mean as the upper limit for normal values, samples greater than 43 micrograms/ml were considered positive. Patients with osteoarthritis were negative; high levels of C1q-bearing immune complexes were detected in patients with rheumatoid arthritis (up to 800 micrograms/ml equivalents of aggregated IgG). With our assay C1q-bearing immune complexes were detected with high frequency (81%) in the sera of patients with rheumatoid arthritis, while a C1q solid-phase binding assay (C1q SPBA) revealed positive results only in 67% of rheumatoid arthritis sera. Compared to NHS, CH50 titers and C1q values of sera from patients with rheumatoid arthritis were frequently high. In contrast, the sera of SLE patients with low CH50 titers and low C1q levels had IgG immune complexes which could be detected only in the C1q-SPBA. C1q-bearing immune complexes were not detectable in the sera of patients with SLE. Since C1q triggers activation of the classical C pathway, this assay with monoclonal anti-C1q antibody appears to be useful for detecting immune complexes in rheumatoid arthritis patients with normal or elevated CH50 and C1q values, especially in the early stage of the disease.

Antibodies, Monoclonal↗
PubMed1987

Evaluation of anti-C1q capture assay for detecting circulating immune complexes and comparison with polyethylene glycol-immunoglobulin G, C1q-binding, and Raji cell methods.

An anti-C1q capture method kit (C1q-immunoglobulin G [IgG]) (Ortho Diagnostics, Inc., Raritan, N.J.) for measuring circulating immune complexes (CIC) was evaluated. The kit showed poor diagnostic sensitivity (P less than 0.005) for identifying CIC in patients with systemic lupus, rheumatoid arthritis, and bacterial endocarditis, as compared with polyethylene glycol-IgG and Raji cell tests (12, 24, and 24 positive, respectively, of 31 patients). Of the patients who were positive with the C1q-IgG test, 25% showed discrepancies when their results were compared with the polyethylene glycol-IgG and C1q-binding test results. Gel filtration chromatography of two of these discrepant sera showed the only peak of C1q-IgG activity to be associated with monomeric IgG (molecular weight, less than 200,000). We concluded that the kit method may be measuring substances other than CIC in some sera, because molecules of C1q attached to IgG should exhibit a molecular weight of greater than 500,000.

Antigen-Antibody Complex↗
PubMed2002

C1q deficiency and autoimmunity: the effects of genetic background on disease expression.

Gene-targeted C1q-deficient mice have been shown to develop a syndrome reminiscent of human systemic lupus erythematosus with antinuclear Abs and proliferative glomerulonephritis. Initial phenotypic analysis conducted in (129 x C57BL/6) hybrid mice showed that background genes were a significant factor for the full expression of the autoimmune disease. To assess the contribution of background genes in the expression of the autoimmune phenotype, the disrupted C1qa gene was backcrossed for seven generations onto C57BL/6 and MRL/Mp(+/+) strains. These were intercrossed with C57BL/6.lpr/lpr and MRL/Mp-lpr/lpr strains to generate C1q-deficient substrains. In C1q-deficient C57BL/6 mice, no evidence of an autoimmune phenotype was found, and C1q deficiency in both the C57BL/6.lpr/lpr and MRL/Mp-lpr/lpr strains did not modify the autoimmune phenotype observed in wild-type controls. However, in C1q-deficient MRL/Mp(+/+) animals an acceleration of both the onset and the severity of antinuclear Abs and glomerulonephritis was seen. Disease was particularly pronounced in females, which developed severe crescentic glomerulonephritis accompanied by heavy proteinuria. In addition, the C1q-deficient MRL/Mp(+/+) mice had an impairment in the phagocytic clearance of apoptotic cells in vivo. These data demonstrate that the expression of autoimmunity in C1q-deficient mice is strongly influenced by other background genes. The work also highlights the potential value of the C1q-deficient MRL/Mp(+/+) strain as a tool with which to dissect further the underlying mechanisms of the autoimmune syndrome associated with C1q deficiency.

Animals↗
PubMed1991

Phagocytic cell molecules that bind the collagen-like region of C1q. Involvement in the C1q-mediated enhancement of phagocytosis.

C1q binds to and elicits cellular responses by several cell types, including monocytes, macrophages, neutrophils, B cells, and fibroblasts. The cell-binding domain is located within the collagen-like pepsin-resistant region of the C1q molecule (C1q tails). An affinity matrix of C1q tails coupled to Sepharose was used to select C1q-binding proteins from detergent extracts of surface-iodinated human monocytes, polymorphonuclear leukocytes, and the U937 cells. The major radiolabeled polypeptide eluted specifically from the ligand affinity column had an apparent molecular mass (Mr) of 126,000. Minor iodinated components eluted from Sepharose-tails migrated with Mr of 216,000 and 55,000. When subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions no change in the migration of any of these polypeptide bands was detected. None of these polypeptides reacted with antibodies directed against the integrins alpha 5 beta 1 (fibronectin receptor) or alpha v beta 3 (vitronectin receptor), LFA-1, or to several other cell adhesion molecules. The Mr 126,000 band was found to contain more than one polypeptide. Lectin binding properties, susceptibility to glycosidases and proteases, and immunoreactivity with the monoclonal antibody L-10, indicated that CD43 (sialophorin/leukosialin) is a component of this band. However, further data show that a monoclonal antibody, generated by immunization with the isolated Clq-binding fractions, recognizes a cell surface sialoglycoprotein distinct from CD43 and inhibits the C1q-mediated enhancement of phagocytosis in monocytes. These latter observations provide the first definitive connection between a specific phagocytic cell surface protein and a known C1q-mediated function. While these proteins contain sialic acid, binding assays and functional assays using neuraminidase-treated cells demonstrate that the functional interaction between C1q and the cell surface is not via sialic acid. The data taken together indicate either that the functional C1q receptor on phagocytic cells is a multi-subunit complex or that multiple proteins can interact with the fragment of C1q containing the cell-binding domain, at least one of which is involved in the C1q-mediated enhancement of phagocytosis.

Amino Acid Sequence↗
PubMed1986

[Are C1q binding immune complexes appropriate as markers for infected ventriculo-atrial shunts?].

Routine C1q-fluid phase radioimmunoassay identified high levels of C1q-binding immune complexes in 3 patients with infected ventriculoatrial shunts (VAS). Accordingly, C1q-binding activity was prospectively studied in additional 36. VAS patients to learn whether the observed immune complex activity was secondary to bacterially contaminated shunts or was a normal sequela of continuous intravenous infusion of cerebrospinal fluid into the vascular space. Pathological levels of C1q-binding activity were detected in only 3 out of 32 patients without evidence of shunt infection. However, extremely high C1q-binding activities were measured in 4 more patients with proven shunt infections. Thus, elevated levels of C1q-binding immune complexes correlate with infected VAS. As shunt infection is otherwise difficult to detect, serum C1q-binding activity may prove to be a valuable diagnostic tool for this condition.

Adolescent↗
PubMed1983

Factors influencing the incorporation of fibronectin into synovial fluid cryoprotein.

Methods of synovial fluid collection and processing known to affect cryoprotein formation were examined to investigate the proposed role of fibronectin in synovial fluid cryoprecipitation. Fibronectin, a nonimmunoglobulin, noncomplement synovial fluid protein was present in all resolubilized synovial fluid cryoproteins studied. Radiolabeled fibronectin was precipitated from rheumatoid synovial fluid to a significantly greater extent (10%) than from noninflammatory (osteoarthritic) synovial fluid (2.8%), normal plasma (1.3%), or normal serum (0.5%) (p less than 0.01). Clotting of synovial fluid reduced fibronectin concentration 44% and resulted in a reduction in the amount and percent incorporation of fibronectin into cryoprotein, whereas heparinization and hyaluronidase treatment increased cryoprecipitable fibronectin. Affinity depletion of synovial fluid fibronectin resulted in loss of C1q and reduction in IgG in the cryoprotein; however, fibronectin, C1q, and IgG could not be co-eluted from affinity matrices of gelatin and protein A-Sepharose. Cryoprotein formation from pathologic synovial fluid depends in part on fibronectin and appears to involve interactions between fibronectin and fibrinogen as well as immunoglobulin complexes and complement components.

Arthritis, Rheumatoid↗
PubMed1982

Biological significance of the C3 nephritic factor in membranoproliferative glomerulonephritis.

Serum levels of the C3 nephritic factor (C3NeF), an IgG autoantibody directed against the C3bBb convertase of the alternative complement pathway, and of eight complement components (C1q, C4, C3, C3d, C5, C9, fB and properdin) were measured in 109 serum samples from 27 patients with idiopathic membranoproliferative glomerulonephritis (MPGN) (type I, 20 cases, and type II, 7 cases) and 14 patients with secondary MPGN. Correlations between the concentrations of C3NeF, serum complement levels and progression of the renal damage were studied during the course of the disease in 14 patients with C3NeF activity. The results showed that (1) C3NeF activity was more frequent in patients with type II MPGN than in patients with type I disease; nevertheless there was a high incidence of this splitting activity in patients with secondary MPGN, (2) high levels of the complement components were present in patients with MPGN, (3) low levels of C3 occurred frequently in type II disease and in secondary MPGN, (4) there was no correlation between C3, fB and C3NeF levels, (5) the presence of C3NeF was associated with a more rapid deterioration of renal function. Longitudinal studies showed that serum levels of C3NeF were not satisfactory for monitoring the clinical course of the illness and, in this respect, are similar to the levels of other autoantibodies in patients with autoimmune disease. As MPGN is a clinical syndrome with various pathogeneses, we suggest that the autoantibody, C3NeF, should be considered only as a marker of some forms of MPGN.

Autoantibodies↗
PubMed1983

C1q has albumin binding activity but does not interfere in the hemagglutination test for anti-albumin antibodies.

Two factors in the sera of patients with liver disease interact with polymerized human serum albumin (HSAP). These are anti-albumin antibodies (AAA) and receptors for polymerized albumin on HBsAg. Recently it was demonstrated by radioimmunoassay that purified human C1q also binds HSAP. Our data confirm the reaction between purified human C1q and HSAP by passive hemagglutination and by indirect immunofluorescence of HSAP-coated erythrocytes (E-HSAP). It is shown that although purified C1q binds HSAP, in the serum, the AAA and not C1q are responsible for the albumin binding activity in HBsAg-negative sera of patients with liver disease and of normal individuals, as detected by passive hemagglutination of E-HSAP, AAA were found to inhibit the binding of serum C1q to polymerized albumin, and hence the E-HSAP hemagglutination test for AAA titration in human sera proved valid.

Antibodies↗
PubMed1985

Effect of the C1q on the soluble collagen-platelet interaction.

The mechanism by which C1q inhibited soluble collagen-induced platelet aggregation was examined. Platelet aggregation induced by soluble collagen in gel filtrated platelets was inhibited by the addition of C1q. There were no cross-reactions between C1q, purified soluble collagen receptor and both of their polyclonal antibodies in enzyme-linked immunosorbent assays. These results suggest that the effect of C1q on soluble collagen-induced platelet aggregation does not compete at the same binding site on the platelet surface.

Animals↗
PubMed2004

A role for lipid rafts in C1q-triggered O2- generation by human neutrophils.

Calreticulin, a candidate C1q receptor, was shown recently to be present on the surface of human neutrophils in association with glycosylphosphatidylinositol (GPI) anchored proteins, particularly CD59. In this study, we show that antibodies to CD59, as well as to every other GPI-anchored protein tested, inhibited the C1q-triggered release of O(2)(-) from PMN. Methyl beta cyclodextrin (M beta CD) treatment of the cells to disrupt lipid rafts also prevented C1q-triggered O(2)(-) production. beta(2) integrin-dependent co-stimulation is required for O(2)(-) production from PMN, however M beta CD had no effect on LFA-1 or Mac-1-mediated adhesion, soluble iC3b binding to PMN, or spreading and migration, all of which suggested that PMN integrin function remained intact. Flow cytometric analysis of PMN treated with M beta CD showed upregulation of PMN granule-associated integrins and a corresponding increase in integrin activation-reporter epitopes, in contrast to the decreased expression of GPI-anchored antigens. These data support a model where lipid rafts and their associated GPI-anchored proteins are critical for C1q-triggered O(2)(-) production, consistent with a model where calreticulin serves as the C1q receptor for O(2)(-) production from PMN.

Antibodies↗
PubMed2002

Correlation between the renal C1q deposition and serum anti-C1q antibody: a potential role of anti-C1q antibody in lupus nephritis.

The anti-C1q antibody has been shown to be associated with lupus patients with renal involvement. We conducted a study to determine the relationship between the serum anti-C1q titer and the renal deposition of C1q. The serum anti-C1q was measured in 26 healthy controls and 47 systemic lupus erythematosus (SLE) patients who were divided into 2 groups as non-nephritis and nephritis SLE. We analyzed the relationship between the anti-C1q titers and SLE, renal C1q staining and the WHO classification for lupus nephritis. The result revealed that the serum anti-C1q was present in 50.8% of the SLE patients, that its levels in those with renal involvement were significantly higher than in the normal control group (61.540 +/- 87.720 U/ml vs 15.750 +/- 2.530 U/ml, p = 0.005). Besides, the serum anti-C1q levels were higher in the patients with lupus nephritis with C1q deposition in the kidney tissue (66.038 +/- 91.141 U/ml vs 16.652 +/- 3.097 U/ml, p < 0.01). There seems to be evidence supporting that the autoantibody anti-C1q might play a pathogenic role in lupus nephritis.

Adult↗