Complement activation during normal pregnancy.
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Complement Activation↗
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Results for “Complement C3c”
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Functional expression of human CD59 in transgenic mice.
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Animals↗
Analysis of a polyacrylamide gel electrophoretogram of beagle serum protein by laser densitometer.
Beagle serum proteins were separated by polyacrylamide gel electrophoresis (PAGE) and the electrophoretograms were examined by one- and two-dimensional analyses with a laser densitometer. In order from the anodic side of the PAGE pattern, pre-albumin, hexokinase, tyrosinase, alkaline phosphatase, urease, and aldehyde dehydrogenase were assumed to be present based on Rf and Mw. Serum albumin, lactate dehydrogenase, and catalase appeared to be present based on a comparison of their electrophoretic mobility with that of protein standards of known Mw. Verification of beagle serum protein fractions by immunofixation electrophoresis and western blotting electrophoresis, with rabbit anti-human serum, indicated alpha 1-antitrypsin, albumin, haptoglobin, ceruloplasmin, C3c complement, IgG, and IgA. Serum protein fraction values (%) obtained by one- and two-dimensional analyses were similar.
Animals↗
Hereditary complement factor I deficiency.
We describe four cases (from three families) of hereditary factor I deficiency, bringing the total number of cases now reported to 23. In one family there are two affected siblings: one has suffered recurrent pyogenic infections; the other is asymptomatic. In the second family, the patient had recurrent pyogenic infections and a self-limiting vasculitic illness; in the third family, the patient suffered recurrent pyogenic and neisserial infections. All four patients had markedly reduced concentrations of C3 in the serum (family 1 propositus: 28%; family 1 asymptomatic sibling: 15%; family 2: 31%; and family 3: 31% normal human serum) which was in the form of C3b. Low IgG2 levels may occur in primary C3 deficiency, and a reduction in IgG2 concentration to 1.14 g/l (normal: 1.30-5.90 g/l) was found in the patient from family 2. Using radioligand binding assays, we demonstrated increased binding of C3b to erythrocytes in a patient with factor I deficiency. This C3b could not be cleaved by autologous serum but could be cleaved by normal serum or purified factor I. We review and compare the published cases of C3, factor H and factor I deficiency.
Adolescent↗
Decay-accelerating factor transgenic mouse hearts are protected from human complement-mediated attack.
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Animals↗
[Usefulness of immunologic and protein determinations for assessment of exposure to mercury].
The count of lymphocytes, lymphocytes T (CD 3+), lymphocytes T-helper (CD 4+), T-suppressor (CD 8+) and NK-cells (CD 16+) as well as immunoglobulins A, D, G, M, complements C3c and C4, alpha 1-acid glycoprotein, haptoglobin, ceruloplasmin and transferrin were detected in males exposed to mercury vapours and in males of the control groups. The shift time weight average (TWA) of mercury in ambient air was 0,028 mg x m-3. Mean mercury concentration was from 0 to 240 micrograms x 1(-1) in urine of the study group and from 0-30 micrograms x 1(-1) in blood. Stimulation of lymphocytes system, manifested by an increase number of lymphocytes T, T-helper and T-suppressor in the peripheral blood was observed. Higher increase of T-suppressor cells than T-helper populations was the case of decreased value of the T-helper/T-suppressor ratio by 20.5% (p < 0.05) in workers exposed below 10 or by 21% (p < 0.05) in workers exposed over 10 years. Decrease of immunoglobulin A, G and M concentration in serum of workers exposed to mercury vapours over 20 years was also observed. The concentrations of IgG, C3c, C4 and determined acute phase proteins in serum of exposed subjects did not differ from that in the non-exposed subjects.
Acute-Phase Proteins↗
Clinical significance of complements in ascitic diseases: elevated complement levels disapproving the liver disease origin.
In a two-year period, ascitic fluid concentrations of complement 3c and complement 4 were measured in 110 patients with sterile cirrhotic ascites, 31 patients with spontaneous bacterial peritonitis, 65 patients with hepatocellular carcinoma, 36 patients with peritoneal carcinomatosis and 12 patients with miscellaneous diseases (nephrotic syndrome 4, systemic lupus erythematosus 3, secondary peritonitis 2, cardiac ascites 1, eosinophilic peritonitis 1 and tuberculosis peritonitis 1) to assess the clinical utility of ascitic fluid complements. The ascitic fluid level of complements 3c or C4 was significantly higher in patients with peritoneal carcinomatosis (32.8 +/- 10.2, 13.4 +/- 7.4 mg/dL) than in patients with sterile cirrhotic ascites (9.2 +/- 5.2, 4.5 +/- 3.9 mg/dL, p < 0.001), spontaneous bacterial peritonitis (8.2 +/- 4.1, 3.8 +/- 2.4 mg/dL, p < 0.001) or hepatocellular carcinoma (12.8 +/- 8.3, 5.6 +/- 4.4 mg/dL, p < 0.001). However, it was not significantly different from the miscellaneous disease group. To verify that ascites formation is not related to liver disease origin, diagnostic sensitivity, specificity and accuracy were 83.3%, 92.7% and 90.9%, respectively, by the ascitic fluid level of complement 3c higher than the cut-off value (20 mg/dl); or 60.4%, 89.8% and 84.3%, respectively, by the ascitic fluid level of complement 4 higher than the cut-off value (10 mg/dL). A direct correlation was found between the ascitic fluid protein level and the ascitic fluid complement 3c (r = 0.70) or complement 4 (r = 0.57) level. Based on results in this study, we can conclude that measuring ascitic fluid complements is clinically useful in disapproving the liver disease origin of ascites formation. However, it is of little value in diagnosing spontaneous bacterial peritonitis or hepatocellular carcinoma.
Ascites↗
Further characterization of a complement-sensitive mutant of a virulent avian Escherichia coli isolate.
An attempt was made to characterize the mechanism of complement resistance operating in a virulent avian Escherichia coli isolate. Using flow cytometry to detect antibody to C3, we found that there was significantly more antibody bound to a complement-sensitive mutant of this wild type than to the parent organism, suggesting that more C3 subunits were bound to the wild type. Neither the wild type nor the mutant degraded C3. Further, the mutant was phagocytosed to a significantly greater degree than the wild type by cultured phagocytes in the presence of C5-deficient serum. These data suggest that the wild type is resistant to complement, at least in part, because of its ability to restrict C3 deposition on its surface. Therefore, the decrease in virulence seen in the mutant may be related to its increased sensitivity to complement-mediated bacteriolysis or its enhanced susceptibility to complement-opsonized phagocytosis or both.
Animals↗
Evaluation of prognostic significance of circulating interleukin-6 in patients with accident spine injuries.
Our study aimed to verify whether patients with spine accident injury present altered plasma levels of IL-6 and whether the levels of this cytokine are related with the production of acute phase proteins which are elevated after trauma and infection. 34 subjects admitted to an Intensive Care Unit for spine injuries were examined: 26 presented fever over 38.5 degrees C and in 13 of them blood or local cultures were positive for pathogenic bacteria. IL-6, C-reactive protein (CRP), haptoglobin (HPT), alpha 2-macroglobulin (alpha 2Mg), C3c and C4 Complement factors were determined on admission and in the course of their hospital stay. No changes in IL-6 systemic levels were present in the subjects examined and only CRP was constantly high. Although within the normal range IL-6 levels inversely correlated with fever. Our results show the difficulty to utilize the IL-6 circulating levels as prognosis parameter in patients subjected to spine accident injuries.
Accidents↗
Development and clinical application of electroimmunoassays for the direct quantification of the complement C3 split products C3c and C3d.
The present report describes the development of electroimmunoassays for the direct quantification of C3d and C3c, split products of the third complement factor (C3). Both methods were developed as rocket immunoelectrophoreses, using two antibody preparations with specificities against the C and D epitopes on C3. A stable calibrator preparation for C3c and C3d was produced by autolytic cleavage of C3. Investigations of patients with anaphylactic reactions or chronic immunological disorders showed that quantification of C3c and C3d in plasma by these methods reflected the degree and rate of complement activation. C3d determination was found to be the most sensitive and reliable indicator of C activation, both during acute and chronic activation since C3c is eliminated considerably faster from the circulation than C3d (estimated half lives of 2 h and 4 h, respectively). Treatment of rheumatoid arthritis patients with prednisolone caused a prompt decrease of plasma C3d values, indicating that the clinical effect may be due to inhibition of complement activation.
Antibody Specificity↗
Immunological and clinical follow up of hepatitis C virus associated cryoglobulinaemic vasculitis.
OBJECTIVE: To study immunological markers and compare these markers with standard measures for the clinical and immunological follow up of vasculitis activity in hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis (CV). METHODS: Serial serum samples from eight patients with newly diagnosed HCV associated CV were followed during interferon alpha treatment induced remission of the CV. Vasculitis activity and disease extent were evaluated with the Birmingham vasculitis activity score (BVAS) and disease extent index (DEI). Cryoglobulinaemia, complement levels (C3c, C4, and CH50), rheumatoid factor (RF), autoantibodies such as antinuclear antibodies, soluble interleukin 2 receptor (sIL2r), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble CD30 (sCD30) were determined. RESULTS: All patients achieved either complete or partial remission of their CV during interferon alpha treatment. There was a significant reduction in vasculitis activity and disease extent (BVAS, DEI), cryoglobulinaemia, RF, sIL2r, sICAM-1, and sCD30. Complement C3c levels increased significantly during this period. Erythrocyte sedimentation rate and levels of complement C4 and CH50 did not change significantly. Both clinical measures (BVAS and DEI) correlated significantly only with C3c and sCD30. CONCLUSIONS: Although this study was of only a small group of patients, it shows that BVAS and DEI as clinical measures and C3c and sCD30 as immunological markers may be useful in the follow up of disease activity of HCV associated CV. The data indicate that activity of the humoral (cryoglobulinaemia, RF, autoantibodies) and cellular (sIL2r, sICAM-1, sCD30) immune response and endothelial damage (sICAM-1) are found in HCV associated CV.
Antibodies, Antinuclear↗
Complement levels of C4, C3C, factor B, and C1 inactivator in peripheral and retroplacental blood of parturient women with EPH gestosis.
The complement levels were determined in 54 parturient women with EPH gestosis, in 32 normal parturient women and in 24 normal non pregnant women. Complement components: C4, C3c, factor B /Bf/ and C1 inactivator /C1 INA/ were measured by radial immunodiffusion. Peripheral and retroplacental blood were examined. Concentrations of C4, C3c, Bf in peripheral blood of both groups of parturient women were significantly higher than in normal non pregnant women. Peripheral blood of parturient women with EPH gestosis contained significantly higher concentrations of C3c than in normal parturient women. Complement Bf levels of normal parturient women were lower in the retroplacental blood than in the peripheral. The levels of C4 were significantly decreased and C3c increased in the retroplacental blood of parturient women with EPH gestosis when results were compared with retroplacental blood of normal parturient women. Results of present study suggest that complement activation could contribute to the pathogenesis of EPH gestosis.
Complement C1 Inactivator Proteins↗
[Fibrinolysis and complement-system profiles during aorto-femoral bypass implantation].
In 51 patients undergoing either implantation of an aortofemoral bypass (38 patients) or of an saphenous bypass (13 patients) the fibrinolytic and complement system profiles were determined. During the course of an aortofemoral bypass the plasminogen concentration decreased by 40%, alpha 2-macroglobulin by 25%, the complement factor C3c by 20% and the complement factor C4 by 40%. Antithrombin III concentration remained stable until the third postoperative day. The alpha 1-antitrypsin concentration increased postoperatively by 40% compared to the preoperative control. The concentrations of plasminogen, antithrombin III, alpha 2-macroglobulin and complement factor C4 did not change in the patients undergoing saphenous bypass operation. Intraoperatively the complement factor C3c decreased by 20%, while alpha 1-antitrypsin showed postoperatively an increase by 30%. Anaesthesia (neuroleptanaesthesia, halothane- or continuous thoracal epidural anaesthesia) had no influence on the fibrinolytic and complement system profiles. Neither could a correlation be shown between the intraoperative haemodynamic changes and the concentrations of the factors of the fibrinolytic and complement system.
Anesthesia, General↗
Complement activation during cardiopulmonary bypass by heparin-protamine interaction.
Circulating concentrations of split products of the third complement factor (C3c and C3d) were measured in five patients before, during and after cardiopulmonary bypass. In all patients, C3d concentrations increased significantly in samples obtained after the administration of protamine sulphate. Similarly, circulating C3c was seen only in those samples obtained immediately after protamine administration. In vitro experiments demonstrated that activation of the complement system was attributable to the heparin-protamine complex, and was dose-dependent. The activation of complement was not associated with any clinically detectable adverse effects.
Adult↗
Molecular cloning and sequencing of porcine C5 gene and its association with immunological traits.
The complement system helps in the lysis of invading pathogens and modulates the inflammatory as well as the humoral and cellular immune responses. C5 mediates many potent inflammatory and cytolytic events after proteolytic activation by complement convertase enzymes. Hence, to investigate the role of pig C5 ( pC5) as a candidate gene for disease resistance in pigs, the complete cDNA of pC5 was sequenced, screened for single nucleotide polymorphisms (SNPs), and an association analysis with various immunological parameters measured in F2 animals of a pig resource population based on a cross of Duroc and Berlin miniature pigs (DUMI) was carried out. In total, 5,422 bp of pC5 cDNA was sequenced, which codes for the 1,677-amino-acid precursor of C5. Four polymorphic sites were detected, one of which was segregating in the DUMI population in three genotypic patterns: AA, AC and CC. Classical (CH50) and alternative (AH50) complement activities, C3c levels, haptoglobin (HP) acute phase protein levels, and antibody titers against Mycoplasma (Mk) and Aujesky (ADV) vaccines were measured in the resource population. Association analysis between C5 and the immunological parameters was carried out using repeated measures mixed and general linear model analysis. The homozygote AA was found to be significantly different from the other two genotypes with respect to AH50 and CH50, whereas genotype CC was found to be significantly different from the other genotypes for C3c and HP levels. No significant difference could be seen between genotypes for antibody titers against vaccinations. Association of C5 with complement activity traits and acute phase proteins promotes pC5 as a candidate gene for innate disease resistance.
Acute-Phase Proteins↗
[Circulating immune complexes in hypertrophic cardiomyopathy and ischemic heart disease].
In 32 patients (pts) with hypertrophic cardiomyopathy (HC), 20 pts with ischaemic heart disease (IHD) and 30 healthy controls, the levels of circulating immune complexes (CIC), immunoglobulins A, G and M, C3c and C4 components of the complement, as well as haemolytic activity of the complement were measured. CIC were assessed using two different methods: a) precipitation with 3% polyethylene glycol with subsequent spectrophotometric measurement of protein content in the precipitate, and b) binding with J-125 labelled staphylococcal +protein ++ A. Pts with HC showed a statistically significant increase in concentration of IgM and the immune complexes (shown with both methods) together with a decrease in C4 and hemolytic activity of the complement. In addition an analysis carried out for each individual patient showed that in some cases an increase in immune complexes concentration was paralleled by a decrease in IgG, C4 and haemolytic activity of the complement. This may suggest that in these pts activation of the complement through the classical pathway can occur. In pts with IHD an increase in immune complexes concentration was demonstrated by precipitation method only. Immune globulines and complement components were within limits for the control group. This suggests that in IHD the complement system is not engaged. Our findings indicate that in HC mechanisms other than those present in myocardial ischaemia must be engaged in inducing changes in the immune system.
Antigen-Antibody Complex↗
[Immunological aspects of pulse therapy in systemic lupus erythematosus].
Twenty SLE patients were examined against a background of pulse-therapy with methylprednisolone. The analysis showed that there was a decrease in the CIC concentration, antibodies to native DNA and an increase in the level of C3c and C4 components of the complement against a background of pulse-therapy. A more rapid time course of the CIC level was noted shortly after pulse-therapy as compared to changes in other immunological indices. A dynamic study of immunological indices in SLE against a background of pulse-therapy was appropriate for a clinical assessment and a study of the mechanisms responsible for the therapeutic efficacy of this method.
Adolescent↗
[Evaluation of C3c, C4 and C1-esterase inhibitor (C1-INH) during unstable angina].
BACKGROUND: The complement system plays an important role in the physiopathology of acute myocardial infarction (AMI) taking part in myocardial damage and reperfusion injury. The aim of this study is to investigate the plasmatic levels of some complement components (C3c, C4 and C1-INH) during unstable angina (C1-INH) and their different concentrations in relation to the different myocardial areas affected by ischemia. METHODS: The plasmatic levels of C1-INH, C3c and c4 in 30 patients affected by unstable angina, and those of 22 clinically healthy subjects (control group) were evaluated (Nefelometer Behering). The patients were divided into four groups according to the different myocardial area affected by ischemia (anterior, antero-lateral, lateral or inferior ischemia), RESULTS: No statistically significant differences were found in plasmatic levels of C3c, C4 and C1-INH between the group of patients and the control group. There is a statistically significant difference between the C1-INH levels of the patients with inferior ischemia and the plasmatic concentrations of the whole patients' group (p<0,01), the control group (p<0,01) and the group of patients with lateral ischemia (p<0,02). CONCLUSIONS: There seems to be a different activation of the complement system during unstable angina, in relation to the different myocardial area affected by ischemia.
Aged↗