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Associations between clinical disease, circulating antibodies and C1q-binding immune complexes in human onchocerciasis.

Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non-specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested. The levels of non-specific immune complexes (NS-IC) in these sera were measured by a solid phase radio-immunoassay and those of O. volvulus-specific immune complexes (OV-IC) by an assay measuring antibody-excess complexes using C1q-coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either the active destruction of microfilariae (acute changes), or the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method. A negative association between microfilarial load and immune complex level was found, with the higher levels of OV-IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV-IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the presence of ocular lesions. OV-IC levels varied considerably within each age group and from age to age. A weak positive association was detected between microfilarial load and parasite-specific IgG antibody concentration in the sera. On average younger individuals (less than 25 years) had the higher antibody levels with a gradual reduction in mean concentrations with age. The significance of these serological findings in terms of the pathogenesis of onchocerciasis is discussed.

Age Factors↗

Detection of IgG aggregates or immune complexes using solid-phase C1q and protein A-rich Staphylococcus aureus as an indicator system.

A radioimmunoassay for detection of C1q-binding IgG aggregates and antigen-IgG antibody complexes is described. The assay makes use of solid-phase C1q and 32p-labelled protein A-rich Staphylococcus aureus as an indicator system. Both 19S and heavier IgG aggregates that fixed C1q were detected. The sensitivity of the assay permitted detection of heavy (19-25S) IgG aggregates at a concentration of 8 mug/ml or less. The results indicated that detection of IgG in this assay is dependent on the degree of IgG polymerization and the molar ratio between the solid-phase C1q and the IgG polymers. Albumin-anti-albumin complexes, preformed at equilibrium with antibody to antigen molar ratios of 2:1 to 3:1 and at antigen concentrations of 25 to 40 mug/ml, were also detectable using the described radioimmunoassay.

Antigen-Antibody Complex↗

A solid-phase radioimmunoassay for C1q-binding immune complexes. I. Delta IgG as indicator molecule.

A solid-phase radioimmunoassay for detection of circulating C1q-binding immune complexes (IC) or heat-aggregated IgG (delta IgG) is described. Purified human C1q protein was adsorbed to a fixed area of polystyrene tube surface for 1 hr at 22 degrees C, pH 7.3, mu 0.15. Binding of delta IgG or IC to solid-phase C1q at 22 degrees C progressed over several hours and was enhanced at low mu (0.05). Heating of C1q (56 degrees C for 30 min) reduced the binding by 85%-90%. Binding of IC or delta IgG was retained after several weeks' storage of solid-phase C1q at 4 degrees C. Detection of 2-5 ng delta IgG and less than 50 ng IC (in antibody excess) was achieved in competitive binding or inhibition tests with [125I]delta IgG. Preliminary testing of 48 human sera indicated the usefulness of the assay for detection of IC in patient sera.

Adsorption↗

A Clq immunosorbent assay compared with thin-layer gel filtration for measuring IgG aggregates.

A new sensitive technique measures C1q-binding of human IgG aggregates. The method is based on the principle of the enzyme-linked immunosorbent assay with C1q-coated tubes. The IgG aggregates attaching to this C1q are shown by enzyme-linked anti-human IgG. Less than 0.01 mug of aggregates per milliliter of sample can be detected. The results with this new method showed significant correlation (P less than 0.01; Spearman rank correlation test) with the estimates of IgG aggregates of 13S or more and 10S in size obtained by thin-layer gel filtration. Both of these methods showed significant correlation with the classic hemolysis inhibition method for measuring complement fixation.

Chromatography, Gel↗

A family with complement factor I deficiency.

A family with inherited factor I deficiency is described. The proband was a 19-year-old Caucasian female with one episode of meningococcal meningitis and one episode of suspected septicaemia of unknown cause. Two obligate and two probable heterozygotes with factor I levels below the lower limit of the reference range were identified. None of these exhibited increased susceptibility to infectious diseases. The inheritance was autosomal codominant. In addition, molecular heterogeneity of factor H in plasma from the proband but not from any other family members was demonstrated by crossed immunoelectrophoresis. The migration of factor H component of fast electrophoretic mobility was retarded by antibodies to C3c and C3d, suggesting the presence of a fluid-phase complex between factor H and excess C3b generated by the uncontrolled activity of the amplification loop.

Adult↗

Comprehensive evaluation of complement components in the course of type I (Lepra) and type II (ENL) reactions.

Complement components C1q and C4 of classic pathway; C3d, a breakdown product of C3, and factor B of alternate pathway: and C3, a component both of classic and alternate pathways, were studied in 35 patients, comprising 18 type I (Lepra) and 17 type II (ENL) reactions. There was a significant decrease in C3 and factor B with a concomitant rise of C3d during ENL. These changes indicate their preeminent role in immunogenesis of type II (ENL) reaction. The changes in the classic pathway components, on the other hand, were insignificant, apparently suggesting its limited involvement in ENL. Furthermore, reversion of factor B and C3d after subsidence of reaction is intriguing and may indicate that they are not substantially affected even with contemporary treatment. Complement components, of both classic and alternate pathways, showed no significant alterations either during type I (Lepra) reaction or after its amelioration.

Complement Activating Enzymes↗

Hepatic function and fibrinolysis in patients with hereditary angioedema undergoing long-term treatment with tranexamic acid.

Prophylactic treatment with antifibrinolytic agents, epsilon-aminocaproic and tranexamic acid, reduces the incidence and severity of attacks in patients with hereditary angioedema. Long-term effectiveness or risk of antifibrinolytic agents has not been established. Sixteen patients needing continuous prophylaxis because of frequency and severity of attacks were treated with tranexamic acid. In four patients this treatment was ineffective and the drug was withdrawn after 2 months. A remission or reduction in the frequency or severity of attacks was observed in 12 patients treated for a period ranging from 8 to 34 months. Hepatic tests and blood fibrinolytic activity were not influenced by long-term oral treatment with tranexamic acid.

Adolescent↗

Opsonic and physicochemical characteristics of intravenous immunoglobulin preparations.

The composition and opsonizing activity of five commercially available immunoglobulin preparations for intravenous use (Venoglobulin I, Venilon, Gammagard, Polyglobin, and Sandoglobulin) were studied. The composition of these preparations does not differ very much as far as total protein, immunoglobulin class and IgG subclass concentrations are concerned. The only exceptions were that Veniglobulin I, Gammagard and Sandoglobulin contain IgA, which might cause side effects in patients with anti-IgA antibodies, Gammagard contains very little IgG4, and Venilon and Polyglobin contain no and almost no IgG3, respectively, which might explain their very low opsonic activity. It was found that Venilon and Gammagard activate complement in the ready-for-infusion state. The opsonic activity of Venoglobulin I, Sandoglobulin and Gammagard is about equal to that of inactivated serum: Staphylococcus aureus, Escherichia coli with K antigen, Streptococcus pyogenes and Streptococcus group B are well opsonized and E. coli without K antigen and Streptococcus pneumoniae are poorly opsonized.

Blood Bactericidal Activity↗