Serum immunoglobulin and complement (C3) levels: a study in adults with idiopathic, chronic polyneuropathies and motor neuron diseases.
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Adolescent↗
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Results for “Complement C3”
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Family studies on the third component of complement (C3), 1-antitrypsin and pseudocholinesterase polymorphism (locus E 1 and E 2 ) in the area of Marburg (Germany).
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Antigen-Antibody Reactions↗
Deficiencies of human C3 complement receptors type 1 (CR1, CD35) and type 2 (CR2, CD21).
CR1 (CD35) and CR2 (CD21) are structurally related integral transmembrane glycoproteins that function as cellular receptors for human C3b and C3dg, respectively. The primary sequence of the most common structural allotype of CR1 and that of CR2 have been established, and ligand binding on the molecules has been mapped. CR1 and CR2 genes are located in close vicinity in the RCA locus of chromosome 1. CR1 has a wide cellular/tissular distribution and mediates a variety of biologic functions, including the transport of C3-bearing immune complexes on erythrocytes, enhancement of phagocytosis, induction of IL-1 secretion and enhancement of B-cell differentiation. Expression of CR2 is restricted to B lymphocytes and follicular dendritic cells. The receptor modulates B-cell growth. CR2 also serves as the receptor for EBV and determines the cellular tropism of the virus. This review discusses the molecular biology and functional characteristics of CR1 and CR2. It focuses on alterations of expression of the receptors in disease, with particular emphasis on the genetic and acquired factors that contribute to the defective expression of CR1 in patients with systemic lupus erythematosus.
Amino Acid Sequence↗
All forms of human IgA antibodies bound to antigen interfere with complement (C3) fixation induced by IgG or by antigen alone.
Polyclonal human secretory IgA1 and IgA2 antibodies to a bacterial protein antigen Streptococcus mutans AgI/II, and polyclonal human serum IgA1 and IgA2 antibodies to staphylococcal alpha-toxin, were found to interfere with antigen-mediated C3b fixation. In fluid phase, immune complexes of antigen and IgA failed to fix C3b, whereas antigen-IgG complexes did fix C3b. Partial removal of glycan chains with Streptococcus mitis SK96 glycosidases diminished the capacity of IgA antibodies to interfere with antigen-mediated C3b fixation by the alternative complement pathway. The authors conclude that native serum or secretory IgA antibodies suppress C3b fixation, and that the glycan chains play a significant role in maintaining this property.
Antibodies, Anti-Idiotypic↗
CR1(CD35) and CR2(CD21) complement C3 receptors are expressed on normal human thymocytes and mediate infection of thymocytes with opsonized human immunodeficiency virus.
The present study demonstrates that the C3b receptor CR1 (CD35) and the C3dg/Epstein-Barr virus receptor CR2 (CD21) are expressed by 25% and 70% of normal human thymocytes, respectively. The expression of CR2 extends to both CD1+ and CD1- cells in the thymus. Two subsets of CR2+ thymocytes were defined expressing low and high density of the receptor. The CR2++ subset represented 20% of CR2+ thymocytes and co-expressed the CR1 receptor. CR2++ thymocytes expressed an immature CD1dull, CD3-, CD4dull, CD8-, CD7++ phenotype and included a subpopulation of large cells expressing CD34. Twenty percent of thymocytes expressed the CD21 epitope defined by monoclonal antibody BU32, which is involved in the binding of CD23 to CD21. These observations provide a basis for a role for CD21 in the proliferation and differentiation of thymocytes at early stages of maturation. The functionality of CR1 and CR2 on thymocytes was evidenced by the ability of the receptors to mediate infection of cells with complement-opsonized human immunodeficiency virus (HIV). The results may be relevant to the immunopathogenesis of HIV infection.
Child↗
Behaviour of synovial complement C3 and C4 components in inflammatory and degenerative joint diseases, before and after synoviorthesis.
The synovial fluid beta1a (C3) and beta1e (C4) expressed by their ratio to corresponding serum concentrations) were studied in 31 cases of seropositive rheumatoid arthritis (RA+), 5 cases of seronegative rheumatoid arthritis (RA-1), and 15 cases of osteoarthrosis (OA) before osmic acid synoviorthesis on knees. This was repeated after synoviorthesis in the synovial fluid (SF) of 24 RA+, 4 RA-, and 10 OA patients. The following studies were undertaken: (a) the relationship between these components; (b) their correlation with the SF protein concentration and rheumatoid factor titre, when present. This analysis led us to the following conclusions. (1) Before synoviorthesis (a) The SF beta1e is significantly lower than beta1a in RA+. In OA, an inverse phenomenon is observed. (b) The concentration of beta1a and beta1e are proportional to the protein concentration in the SF of OA. A significant inverse relationship between beta1a, beta1e, and the titre of rheumatoid factor is found. (2) after synoviorthesis the same studies performed on knees at the time of one or more relapses shows that the same pathogenetic process is involved and that the immunological mechanism is little influenced by this treatment. In OA also the relapse differs very little from the initial process observed before synoviorthesis.
Arthritis, Rheumatoid↗
Functional and molecular characterization by the CB04 monoclonal antibody of a cell surface structure exerting C3-complement receptor activity.
CB04 monoclonal antibody which reacts with an epitope of a surface molecule expressed on human monocytes has been elicited using peripheral blood lymphocytes as immunizer. The characterization of the monoclonal antibody examined at the phenotypic, molecular, and functional levels indicates that the CB04 antibody defines a structure present on monocytes, tissue macrophages, B cells, polymorphonucleates, and erythrocytes. The molecular weight (220 kD), the tissue distribution in health and disease conditions, and the involvement in relevant biological processes indicate that the CB04 structure is the receptor for the C3b fragment of the complement. The binding of the antibody to the cell surface induces inhibition of the C3bi receptorial function.
Animals↗
Production of chemotactic activity by guinea pig immunoglobulins following activation of the C3 complement shunt pathway.
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Animals↗
Influence of blood transfusion on bactericidal activity of human leukocytes and sera against Yersinia enterocolitica and Salmonella typhimurium.
Patients undergoing joint surgery and blood transfusion were studied. Serum and leukocyte bactericidal tests in vitro against Salmonella typhimurium and Yersinia enterocolitica were carried out preoperatively as well as on the 1st, 3rd and 7th days after the operation. The serum complement (C3 and C4) concentrations were determined at the same intervals. It was found that after blood transfusion the bactericidic activity of sera and the serum C3 complement concentrations were increased. In contrast the killing ability of leukocytes was suppressed.
Blood Bactericidal Activity↗
The significant of complement and immunoglobulin determination in healthy pregnant women and patients with EPH gestoses.
Complements C3 and C4, IgG, IgM, IgA and properdin factor B (PFB) were determined in maternal blood sera, sera from the umbilical cord and amniotic fluid in the group consisting of 30 healthy pregnant women and 30 patients with EPH gestoses. PFB and IgG were measured in urine, as well. Significant decrease of C3 complement in maternal sera and PFB in urine was found in the group with EPH gestoses, while a slight C4 complement enhancement was recorded in both maternal sera and the blood sera from the umbilical cord. PFB was conspicuously increased in maternal blood sera. IgG level was higher in the blood sera from the umbilical cord in comparison with that found in maternal sera in both groups examined. IgG, IgM and IgA levels were decreased in the group of patients with EPH gestoses in all fluids examined, while IgA level was significantly increased in the sera prepared from the blood from the umbilical cord.
Amniotic Fluid↗
The covalent-binding reaction of complement component C3.
The complement protein C3, when activated by limited proteolysis, forms a short-lived reactive intermediate fragment, 'nascent' C3b, which is known to bind covalently to certain surfaces. The characteristics of the covalent binding reaction have been studied by using Sepharose-trypsin as a combined proteolytic activator and binding surface for C3. Binding of C3 to Sepharose-trypsin is saturable, with a maximum of 25-26 molecules of C3b bound per molecule of trypsin. A minimum life-time of about 60 microseconds for the reactive intermediate has been calculated from binding of C3 at saturation. Initial binding efficiencies of over 30% can be obtained at physiological pH and ionic strength. The efficiency of C3 binding to Sepharose-trypsin decreases as pH increases and also shows a slight decline at high ionic strength. The covalent binding of C3 to Sepharose-trypsin can be inhibited by a range of oxygen and nitrogen nucleophiles. Activation of C3 in the presence of radioactive forms of four such nucleophiles, phenylhydrazine, methylamine, glycerol and glucosamine results in apparent covalent incorporation of the nucleophile into the C3d fragment of C3. The quantity of radioactive nucleophile bound can be predicted from the observed potency of the nucleophile as an inhibitor of the binding of C3 to Sepharose-trypsin. The radioactive nucleophiles may be considered as 'active-site' labels for C3.
Binding Sites↗
[Level of the C3-component of complement in the blood serum of sick children].
The levels of the complement C3 component have been measured in children with various diseases (immunodeficiency states, food allergy, rheumatoid arthritis, severe and medium-severe forms of acute respiratory viral infections), and the complement consumption in the course of alternative activation has been examined. The findings evidence a relationship between the complement C3 component consumption and the blood serum IgA level, as well as between the C3 level and the neutrophilic phagocytic and metabolic activities.
Arthritis, Rheumatoid↗
Amino acid sequence analysis of the glycopeptides from human complement component C3.
Human complement component C3 has been cleaved completely by trypsin in the presence of 2-propanol. The hydrolysate was fully solubilized and fractionated by reversed-phase HPLC. Two peptides only contained glucosamine, Unambiguous sequence analyses identified Asn-63 of the beta-chain and Asn-268 of the alpha-chain as the sites of carbohydrate attachment. A third potential Asn-Xaa-Thr/Ser glycosylation site, Asn-946 of the alpha-chain, is not modified. The different states of glycosylation of the sites cannot be explained by differences in exposure or secondary structure. All three are predicted reverse turn.
1-Propanol↗
Serum matrix metalloproteinase-9 is elevated in men with a history of myocardial infarction.
Elevated serum inflammatory markers have been reported in coronary heart disease. Levels of serum matrix metalloproteinase-9 (MMP-9), C-reactive protein (CRP), C3-complement (C3) and autoantibodies against oxidized low-density lipoprotein (oxLDL) in 120 male subjects with a history of myocardial infarction (MI) were compared with those in 250 age-matched controls, both groups from a large cross-sectional population survey, the FINRISK study. The concentrations of serum MMP-9 and autoantibodies against oxLDL were measured by enzyme-linked immunosorbent assay, CRP and C3 by immunonephelometry. MMP-9, CRP and C3 concentrations were higher in the subjects with a history of MI than in the controls (p=0.037, p=0.004, and p=0.006, respectively). There was no difference between the groups in serum levels of autoantibodies against oxLDL. In other background characteristics, men in the MI group had higher body mass index (BMI) and serum triglyceride values and lower serum HDL cholesterol values compared to controls (p=0.009, p=0.001, and p<0.001, respectively). When analyzed by stepwise multiple logistic regression using BMI, HDL cholesterol, triglycerides, CRP, C3 and MMP-9 as independent variables, the significant predictors for MI were HDL cholesterol (p=0.002) and MMP-9 (p=0.015). These results suggest that increased serum MMP-9 may reflect inflammatory pathologic processes that are related to progression of atherosclerosis.
Aged↗
Diagnostic validity of multivariate combinations of biochemical analytes as markers for rejection and infection in the follow-up of patients with heart transplants.
The diagnostic validity of multivariate combinations of alpha 1-antitrypsin, alpha 2-macroglobulin, C-reactive protein, complement C3, complement C4, neopterin in serum, and neopterin in urine as markers for acute cardiac allograft rejection and for differential diagnosis of rejection and infections was investigated in the follow-up of 37 patients with heart transplants. Rejection was diagnosed by endomyocardial biopsy. Infections were classified as 'no infection', 'viral infection', and 'bacterial, fungal or mixed infections'. Although there are significant differences between the mean levels of analytes, multivariate discriminant analysis does not provide an adequate discrimination of rejection and infection states. In separate rejection diagnosis, multivariate combinations of analytes cannot replace endomyocardial biopsy. However, a multivariate combination of alpha 1-antitrypsin, alpha 2-macroglobulin, C-reactive protein, C3, C4 in serum, and neopterin in urine can be used as a screening procedure to reduce the number of endomyocardial biopsies.
Adolescent↗
Recombinant rat IL-1beta and IL-6 synergistically enhance C3 mRNA levels and complement component C3 secretion by H-35 rat hepatoma cells.
Hepatic synthesis of complement component C3 is regulated in part by inflammatory cytokines. Rat models are frequently employed to investigate pathogenic roles of complement and cytokines. However, cytokines obtained from species other than the rat were used in previous studies of cytokine regulation of C3 synthesis in rat hepatocytes or hepatoma cells. It is not known whether these prior reports predict hepatocellular responses evoked by rat cytokines. Therefore, H-35 rat hepatoma cells were employed to measure the effect of recombinant rat IL-1beta, IL-6, IFN-gamma, and TNF-alpha on C3 protein secretion and C3 mRNA levels quantified by ELISA and quantitative RT-PCR. Compared to untreated control cells, H-35 cells treated with IL-1beta, IL-6, and IFN-gamma increased C3 secretion approximately 10-, 4-, and 2-fold, respectively. TNF-alpha was toxic, precluding further analysis. IL-1beta and IL-6 demonstrated synergy with respect to the quantity and rate of increase of C3 mRNA measured and the magnitude of C3 protein secretion. Previous reports using non-rat cytokines did not consistently predict H-35 responses to rat cytokines. Consequently, we recommend the use of rat cytokines in rat models that include analysis of cytokine-mediated events.
Animals↗
Determination of reference intervals for 10 serum proteins measured by rate nephelometry, taking into consideration different sample groups and different distribution functions.
Reference intervals were established for 10 serum proteins (IgA, IgG, IgM, transferrin, haptoglobin, complement C3, complement C4, alpha 1-acid-glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin) measured by rate nephelometry. The reference individuals - 200 blood donors - were divided into 5 subgroups: men aged 19-39 and 40-60 years, women aged 19-39 and 40-60 years and women aged 19-48 years using oral contraceptives. Where possible, two or more subgroups were combined to give reference sample groups. Criteria for this procedure are given. The reference limits of the sample groups were estimated by parametric methods. Assuming that for a specified serum protein the type of distribution is the same in each subgroup, the data were standardized with estimated group specific parameter values and combined into one big sample. This permitted an improved determination of the underlying type of distribution. As a possible form of distribution we also considered the normal distribution truncated on the left side at c greater than or equal to 0. In some cases, after determination of an optimal c, this unusual distribution fitted the data significantly better than the generally used normal or log-normal distribution.
Adult↗
A quantitative method for assessing the third complement factor (C3) attached to the surface of opsonized Pseudomonas aeruginosa: interrelationship between C3 fixation, phagocytosis and complement consumption.
A direct enzyme-linked immunoassay is described for the determination of C3 that becomes attached to the surface of bacteria upon incubation in serum. The assay uses horseradish peroxidase-conjugated rabbit antiserum specific for human C3. In this study various Pseudomonas aeruginosa strains, Escherichia coli and Staphylococcus aureus were opsonized under different conditions and the amount of C3 fixed to the bacterial surface was measured directly. The extent of C3 fixation was compared with the percentage of phagocytosis by human polymorphonuclear leukocytes and with the complement consumption in the fluid phase. It was demonstrated that C3 fixation closely correlated with the percentage of phagocytosis but not with complement consumption. The method can be performed with relatively simple equipment and could be used in routine laboratories in order to determine the extent of opsonization of Pseudomonas aeruginosa and other bacteria and to detect opsonic defects in the sera of patients.
Complement Activation↗