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Detection of immune complexes in systemic lupus erythematosus with the C1q solid phase assay: correlation with nDNA antibodies and hypocomplementemia.

Three immune complex assays, the monoclonal rheumatoid factor inhibition (mRF), the C1q solid phase (C1q-SP), and the C1q fluid phase binding (C1q-BA) assays, were compared with native DNA antibody (nDNA Ab) titers and serum hemolytic complement (CH50) levels in serial analyses of patients with systemic lupus erythematosus (SLE). No correlation was evident among the immune complex assays. A positive correlation was observed between the C1q-SP and nDNA Ab assays, and a negative correlation was observed between the C1q-SP and CH50 assays. Evidence is presented that these correlations are related to the presence of complement-fixing nDNA Ab. The C1q-SP may be useful in delineating the basis for the unexplained association of nDNA Ab and hypocomplementemia.

Antigen-Antibody Complex↗

Characterization of immune complexes detected by the 125I-C1q binding assay in breast cancer.

The aim of the present study was to isolate and characterize immune complexes measured by the 125I-C1q binding assay in breast cancer sera. The C1q binding assay detects immune complexes by their binding to 125I-C1q and subsequent precipitation with PEG. We purified the C1q binding material from these precipitates by superose 6 gel filtration and cation exchange chromatography. The isolation steps were monitored by the C1q binding assay and the purified material was analyzed by SDS--PAGE and immunodiffusion. The C1q binding material isolated from two breast cancer sera contained complexes of IgM, C4b binding protein (C4-bp), and C1q. The C4-bp fraction showed significant C1q binding activity which increased after the addition of IgM. This C4-bp was not different from C4-bp isolated from normal serum. The IgM fraction, however, differed from normal IgM by its binding to C4-bp and C1q and its stronger affinity to the cation exchange column. These unique properties were not due to rheumatoid factor activity. They might be caused by a different glycosylation pattern or by complex formation with an as yet unknown polysaccharide antigen.

Antibodies, Neoplasm↗

Interaction of fibronectin with DNA/anti-DNA complexes from systemic lupus erythematosus: role of activated complement Cl in modulation of the interactions.

Fibronectin (Fn) is an integral constituent of the endothelial cell surface and the basement membrane. The mechanism for binding DNA/anti-DNA complexes to Fn was examined in a solid-phase assay. In physiological buffer, a low-affinity binding of DNA was observed with Fn and optimal binding was seen at pH 6.5 and in the absence of Ca2+. Further, the interaction of DNA to Fn was inhibited when DNA was complexed to anti-DNA antibody. However, complement Clq mediated the binding of complexes to Fn at pH 7.4 and it was proportional to the extent of the dissociation of Cl. Cl inactivator (Cl-In) appeared to play a modulating role; whereas at low concentrations (Cl:Cl-In::4: less than 1) it enhanced the binding of complexes to Fn, higher concentrations inhibited the binding. Further, sera from patients with active systemic lupus erythematosus reacted with Fn, which was shown to be dependent on the presence of Clq and was minimally affected by DNase treatment of sera, indicating a relatively minor role of DNA in the direct binding of DNA to Fn. These findings support "circulating immune complex" hypothesis in the pathogenesis of lupus glomerular immune complex deposition disease.

Antibodies, Antinuclear↗

Hereditary angioedema: the use of fresh frozen plasma for prophylaxis in patients undergoing oral surgery.

Six patients with hereditary anagioedema (HAE) undergoing 7 episodes of dental surgery received transfusions with fresh frozen plasma one day before surgery. Although the morbidity observed in these patients following similar procedures had been high, no significant complications of surgery were noted with this therapy. Thus, fresh frozen plasma infusion appears to provide a safe and effective method of prophylaxis in patients with HAE. Following infusion of fresh frozen plasma, serum levels of C4 esterase inhibitor (C1EI) rose transiently, and then fell to preinfusion levels within 1 to 12 days. In all but one patient the rise in C4 was greater than could be accounted for by the amount of C4 infused. In no patient did the level of C1EI or C4 rise to within the normal range. The data raise the question of the role of C1EI in the pathogenesis of angioedema in these patients.

Aminocaproates↗

Hypersensitivity to procarbazine associated with angioedema, urticaria, and low serum complement activity.

Hypersensitivity to procarbazine associated with urticaria, angioedema, and painful joint swelling was found in a 20-year-old student being treated for Hodgkin's disease. A marked fall in complement component activity occurred simultaneously with the development of symtoms. It is suggested that generation of products of complement component activation could be important in the pathogenesis of hypersensitivity to some drugs.

Adult↗

C1q levels in hereditary angioedema.

In 21 affected members from 4 kindreds with hereditary angioedema, serum C1q levels generally were in the lower part of the normal range, with some values clearly below the lower limit of normal. The serum C1q levels in patients with hereditary angioedema were significantly depressed when compared with those in unaffected family members (p less than 0.001) and healthy control subjects (p less than 0.05). serum C1q levels were significantly (p less than 0.01) related to serum C4 levels which have been used as an indicator of disease activity in individual patients. C1q was stable during storage of serum samples at --20 degrees C for 60 days compared to storage at --70 degrees C. These studies indicate that depressed serum C1q concentrations may be seen in patients with hereditary angioedema and that the finding of this abnormality does not exclude the diagnosis.

Angioedema↗

Interaction of bovine immunoglobulins with complement.

Whereas complement (C) in rabbit serum (CR) was bound by bovine antibodies in seven different IgG1 preparations, only two IgG1 preparations could bind the C in guinea pig serum (CGP). Addition of the Clq component of CR to CGP was alone sufficient to render the C-cascade in CGP activable in the presence of bovine erythrocytes sensitized with specific antisera, i.e. reagents. Normal bovine serum was also capable of restoring the haemolytic activity of CGP. However, the bovine serum was much more temperature sensitive than was CR and, as was observed in the sera from MZ twins, it showed considerable variation both in titre values and in prozones when added to CGP.

Agglutination Tests↗