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Results for “Complement C3d”

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PubMedDate not supplied

Analysis of polyethylene glycol precipitates from SLE sera: antibody enrichment in association with disease activity.

Twenty two systemic lupus erythematosus patients were assessed clinically for periods of up to six years. Polyethylene glycol precipitates of serial serum samples were analysed for the presence of autoantibodies by specific enzyme-linked immunoabsorbent assays. Increased enrichment of anti-Ro(SSA) was found to correlate with disease activity. Longitudinal studies of individual patients showed an association between disease exacerbation and enrichment of anti-Ro(SSA), anti-La(SSB) and anti-ssDNA. Circulating immune complexes isolated by anti-C3 affinity chromatography were also found to contain anti-Ro(SSA), anti-La(SSB) and anti-ss DNA and fixation of complement by complexes could be demonstrated. Enrichment of these autoantibodies in renal eluates of two patients with diffuse proliferative glomerulonephritis provided further evidence for a pathogenic role of these immune complexes.

Antigen-Antibody Complex↗
PubMed1991

[Value of the Coombs test in ABO incompatibility].

We studied the ABO haemolytic disease of the newborn in our neonatal unit to consider their serological aspects and clinical importance. 21% of all pregnancies were ABO incompatibles. The direct antiglobulin test was positive in 46 (11.3%) of them. The Elution was positive in all the newborns with direct antiglobulin test positive (Cd+). The anti-A o anti-B antibodies concentration in mothers was higher than 1/128 in 38 (84%). The C3d complement fraction was activated in two newborns. The infants Cd+ were born to group O mothers in all cases, and nobody was premature. Twelve (26%) of Cd+ presented jaundice which need phototherapy, and one moreover exchange transfusion. The direct antiglobulin test is very useful for detect the liable newborns of serious jaundice; therefore, we thing that is suitable to make this test in infants born to group O mothers. The newborns Cd+ did not have significant anemia at first three months of life.

ABO Blood-Group System↗
PubMed1990

[Recurrent post-infectious immune complex glomerulonephritis with persistent activation of the alternative complement pathway].

Recurring upper respiratory tract infections in a previously healthy 4 years old boy led to an acute nephritic syndrome requiring haemodialysis. Renal biopsy showed poststreptococcal like immune complex glomerulonephritis with subepithelial humps, C3 deposition and crescent formation. Renal function improved after methyl-prednisolone pulse therapy. Two relapses occurred in the following six months which responded to immunosuppressive therapy. 21 months following the first presentation the boy has normal glomerular filtration rate but persistent glomerular proteinuria and haematuria. Detailed complement analyses revealed a persistent activation of the alternate pathway.

Child, Preschool↗
PubMed1989

Paediatric coeliac disease and dermatitis herpetiformis: differences in complement activation in relation to diet.

We studied complement (C') involvement in paediatric coeliac disease (CD) and dermatitis herpetiformis (DH) in relation to lesions and function of enteric mucosa and to diet. For this purpose, 50 children affected by CD and 42 affected by DH were subdivided in 3 groups: in the first (I) were included subjects in free diet, in the second (II) children during gluten-free diet (GFD) and in the third (III) subjects after gluten reintroduction in diet. Only in CD we found significant modifications of some C' parameters. In fact C3 and C4 levels increase in II group in GFD (respectively p less than 0.02 and p less than 0.03) and result inversely correlated to an arbitrary score for the evaluation of the enteric histological lesions (p less than 0.02 and p less than 0.01). C3d/C3 ratio levels, as catabolic index of C3, result always greater than normal in both diseases, but significantly decrease only in II group of CD children (p less than 0.02), where they result also positively correlated to the histological score (p less than 0.05). Circulating immune complex-like material is higher in DH, but incidence of pathological values decrease in II group only in CD (p less than 0.04). These data suggest probable significant differences in the pathogenetic mechanisms of CD and DH involving C'.

Antigen-Antibody Complex↗
PubMed1989

Complement receptors.

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Antigens, Differentiation, B-Lymphocyte↗
PubMed1987

Quantification of the complement receptor function on polymorphonuclear leukocytes: its significance in patients with systemic lupus erythematosus.

The function of complement receptors (CR1) on polymorphonuclear leukocytes (PMN) was assessed by C3b mediated binding of immune complexes (IC) to PMN. The binding of IC to CR1 on PMN depends on the activation of the classical complement pathway and was inhibited by the antibody to CR1 or C3b. CR1 function of PMN from patients with systemic lupus erythematosus was reduced compared with those from normal controls or patients with rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1987

Complement activation following multiple injuries.

Complement activation was evaluated by assay of plasma C3dg and the terminal complement complex (TCC) in 19 patients with multiple injuries. In the nine patients with thoracic involvement, statistically significant increase of plasma TCC was found at first sampling (average 90 min post-trauma), and of C3dg after 24 hours. Such increase was not found in the ten patients without thoracic involvement. Heightened granulocyte elastase activity was found in bronchial lavage fluid 90 min after the trauma in three patients with thoracic injury. Pulmonary insufficiency (pO2/FiO2 less than 16 kPa on intermittent positive-pressure ventilation) arose in four patients. All four had raised plasma levels of TCC or C3dg on arrival at the hospital. Six patients with complement activation did not show pulmonary insufficiency. Although the series was relatively small, the results indicate that thoracic injury is particularly associated with complement activation, and that complement activation alone does not suffice to produce post-traumatic pulmonary insufficiency.

Adolescent↗
PubMed1985

Complement activation in primary biliary cirrhosis: an in vitro model.

Increased concentrations of C3dg were demonstrated in plasma from patients with primary biliary cirrhosis (PBC), indicating in vivo activation of C3. Rapid spontaneous C3 cleavage by the classical pathway was observed in vitro in serum and in EDTA plasma reconstituted with Ca++ and Mg++, suggesting the presence of complement-activating substances. On incubation with fresh normal serum, purified polyclonal IgM from patients with PBC induced C1 activation, C4 cleavage, and C3dg formation. No C3 cleavage was observed when PBC-IgM was incubated with a C2-deficient serum. We suggest that the complement activation in vivo in PBC, which occurs predominantly by the classical pathway and is characterized by increased concentrations of C1 activation complexes, decreased C4 concentrations, and hypercatabolism of C3, is attributable to an abnormal IgM population.

Complement Activation↗
PubMed1984

[The anticomplementary activity of 2 intravenous gamma globulin preparations in children with acute lymphatic leukemia].

Children with acute lymphocytic leukemia received gammaglobulin replacement therapy using either one of two i.v. gammaglobulin preparations in order to reduce the frequency and severity of infections during cytostatic treatment. Sera and EDTA-plasma taken prior to each infusion and following each infusion were analyzed for several complement components and immune complexes in order to assess in vivo anticomplementary activity. Preliminary data published in this paper show only little changes in the complement system. This may be related to fact that infusions were well tolerated. IgG-levels could be raised for more than 200 mg/dl by administration of doses around 150 mg/kg body weight.

Adolescent↗
PubMedDate not supplied

Identification of a 35 kD tumor-associated autoantigen in papillary thyroid carcinoma.

Despite its tendency to metastasize and grow multifocally, papillary thyroid carcinoma (PTC), the most common endocrine malignancy, usually displays an indolent clinical course. Although this behavior probably reflects the inherent low growth potential of PTC cells, it has been postulated that the striking inflammatory reaction often present in PTC represents the activation of a protective, tumor-induced immune response. In a recent immunohistochemical study, we reported that immunoglobulin (IgG) and complement (C3d, C4d and C5) are specifically deposited in PTC tumor tissue. Endeavors were then made to isolate and identify tumor-associated antigens. Immunoprecipitation employing the serum and tumor tissue of PTC patients produced two bands by SDS-PAGE, at approximately 34.5 and 35 kD, which were not present in normal thyroid tissue. Three tryptic peptides of the 35 kD band were sequenced, identifying it as a fragment of cytokeratin 1, a structural protein not normally expressed in the thyroid. The results indicate a tumor-specific antibody response against an aberrantly expressed protein in PTC.

Amino Acid Sequence↗
PubMed1985

Immunonephelometric quantitation of complement split product (C3d) plasma levels in rheumatic disease.

A simple method is described for routine quantitative determination of C3d by laser nephelometry after precipitation of intact C3 by polyethylene glycol. Plasmas from 292 patients with different types of rheumatic disease was tested. Elevated C3d levels were a far more common finding than low levels of complement components C3 or C4, but despite the increased sensitivity, the test only seemed diagnostically useful for systemic lupus erythematosus and MCTD. Though a better test than the quantitation of C3 and C4, the value of C3d determination in rheumatic disease seems to be limited.

Adult↗
PubMed2005

Complement component C3d-antigen complexes can either augment or inhibit B lymphocyte activation and humoral immunity in mice depending on the degree of CD21/CD19 complex engagement.

C3d can function as a molecular adjuvant by binding CD21 and thereby enhancing B cell activation and humoral immune responses. However, recent studies suggest both positive and negative roles for C3d and the CD19/CD21 signaling complex in regulating humoral immunity. To address whether signaling through the CD19/CD21 complex can negatively regulate B cell function when engaged by physiological ligands, diphtheria toxin (DT)-C3d fusion protein and C3dg-streptavidin (SA) complexes were used to assess the role of CD21 during BCR-induced activation and in vivo immune responses. Immunization of mice with DT-C3d3 significantly reduced DT-specific Ab responses independently of CD21 expression or signaling. By contrast, SA-C3dg tetramers dramatically enhanced anti-SA responses when used at low doses, whereas 10-fold higher doses did not augment immune responses, except in CD21/35-deficient mice. Likewise, SA-C3dg (1 microg/ml) dramatically enhanced BCR-induced intracellular calcium concentration ([Ca2+]i) responses in vitro, but had no effect or inhibited [Ca2+]i responses when used at 10- to 50-fold higher concentrations. SA-C3dg enhancement of BCR-induced [Ca2+]i responses required CD21 and CD19 expression and resulted in significantly enhanced CD19 and Lyn phosphorylation, with enhanced Lyn/CD19 associations. BCR-induced CD22 phosphorylation and Src homology 2 domain-containing protein tyrosine phosphatase-1/CD22 associations were also reduced, suggesting abrogation of negative regulatory signaling. By contrast, CD19/CD21 ligation using higher concentrations of SA-C3dg significantly inhibited BCR-induced [Ca2+]i responses and inhibited CD19, Lyn, CD22, and Syk phosphorylation. Therefore, C3d may enhance or inhibit Ag-specific humoral immune responses through both CD21-dependent and -independent mechanisms depending on the concentration and nature of the Ag-C3d complexes.

Animals↗
PubMed2000

Complement degradation product C3d in urine: marker of lupus nephritis.

OBJECTIVE: To examine whether serum and urine C3d, a degradation product of C3, correlate with renal and extrarenal lupus activity. METHODS: Serum and urinary C3d levels were measured by ELISA in 15 healthy individuals and 24 patients with systemic lupus erythematosus (SLE) (8 with inactive disease, 7 with active but nonrenal disease, 9 with active lupus nephritis). Disease activity variables like serum C3, C4, and anti-dsDNA antibodies were also measured. RESULTS: The median serum C3d levels were significantly higher (p < 0.01) in patients with active (26 arbitrary units/ml; AU/ml) and inactive SLE (27 AU/ml) compared to healthy controls (11.25 AU/ml); levels were comparable in patients with active renal and extrarenal SLE. On the other hand, urine C3d was elevated only in patients with active SLE; its level was highest in patients with active lupus nephritis (0.87 AU/ml) compared to patients with active extrarenal diseases (0.31 AU/ml; p < 0.05), to patients with inactive lupus nephritis (0.06 AU/ml; p < 0.001), or to levels in healthy individuals (0.06; p < 0.001). Urine C3d showed stronger correlation with disease activity score (SLE Disease Activity Index) than serum C3, C4, anti-dsDNA antibodies, and serum C3d. CONCLUSION: Urine C3d is a good index of active lupus, particularly lupus nephritis.

Adolescent↗
PubMedDate not supplied

Epitope specificities and quantitative and serologic aspects of monoclonal complement (C3c and C3d) antibodies.

Twenty-two monoclonal antibodies to human C3c and ten to C3d were obtained by hybridization after the immunization of mice with complement-coated human red cells and/or purified human complement components. C3c antibodies were variable in their agglutination reactions with cells coated with C3 by antibody in vitro; more consistent and potent reactions with these cells were observed with anti-C3d, and all anti-C3d reacted with red cells coated with C3 in vivo. Immunoradiometric assays were used to estimate antibody concentration, affinity, and epitope specificity. The antibody content in ascitic fluids varied from less than 0.1 mg per ml to 5.6 mg per ml. The estimated values of antibody affinities for Sepharose-coupled C3 ranged from 2.8 X 10(6) l per M to 5.0 X 10(8) l per M; on average, IgM antibodies had higher affinities than IgG antibodies. Competitive binding assays showed that the monoclonal antibodies recognized at least seven different epitopes, four on the C3c and three on the C3d fragment of C3. When the results of serologic and quantitative assays were compared, no convincing relationship was found between serologic performance and epitope specificity, antibody concentration, or affinity. IgM antibodies generally gave higher agglutination scores than IgG antibodies, and Ig class was the only useful predictor of serologic efficacy.

Animals↗
PubMed1985

Correlation of disease activity with circulating immune complexes (C1qbA) and complement breakdown products (C3D) in patients with systemic lupus erythematosus. A prospective study.

Most biologic effects of immune complexes are mediated through the activation of the complement system. The relationship between lupus disease activity and the presence of C3 breakdown products (C3d) and circulating immune complexes (CIC) as demonstrated with the C1q binding assay (C1qbA), was evaluated. Nearly all 13 systemic lupus erythematosus (SLE) patients had a stable disease course in this prospective study, nevertheless, in each patient the profiles of the serologic parameters were quite different. Despite the small number of investigated patients (13), it is concluded that irrespective of the disease activity, the serologic parameters could be either positive or negative. No relationship could be obtained between disease activity and the presence of C3d and/or CIC. Nor was there any evidence that the presence of CIC would indicate increased levels of C3 breakdown products (C3d). This observation argues against a pathogenetic significance of CIC detected by the C1qbA in SLE. In conclusion, the supposed link between the presence of CIC, consumption and activation of the complement system, and the activity of SLE needs further study.

Adult↗