Complement receptors and regulatory proteins: immune adherence revisited and abuse by microorganisms.
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Animals↗
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Results for “Complement C3b”
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Autoimmune reactions in patients with M-component and peripheral neuropathy.
A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, Waldenström's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens.
Adult↗
Complement-fixing properties of human IgA antibodies. Alternative pathway complement activation by plastic-bound, but not specific antigen-bound, IgA.
The complement-fixing properties of human IgA antibodies bound to specific antigen, or coated directly on plastic surfaces, were examined in comparison with those of IgG antibodies. Use was made of antigen-binding (anti-staphylococcal alpha-toxin) IgA and IgG monoclonal antibodies and normal polyclonal IgA and IgG, purified greater than 99.9% by avoidance of denaturing processes. Complement-fixation ELISA was used, with a high density of biotin-conjugated staphylococcal alpha-toxin bound to avidin-coated plates for the efficient capture of antibodies, and conditions were adjusted for the assessment of classical and alternative pathways of complement activation. Although IgA coated directly on plastic surfaces activated the alternative complement pathway in a dose-dependent manner, IgA antibodies bound to antigen failed to fix complement by either classical or alternative pathways. In contrast, IgG antibodies, either bound to antigen or coated directly on plastic, activated complement mainly by the classical pathway. It was concluded that the complexation of IgA antibodies with antigen is insufficient to elicit complement activation: rather a degree of denaturation seems to play a part in the expression of alternative complement pathway-activating properties by IgA.
Complement Activation↗
Factors influencing the development of immune-complex diseases.
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Animals↗
The properdin system: composition and function.
This article summarized the physicohemical data on the factors which compose the properdin system in guinea pig and man. The following other topics are discussed: (1) Activation of the properdin system; (2) Formation of the initiating and amplification C3 convertases; (3) Formation of the C5 convertase, and (4) Regulatory control mechanisms of the properdin system.
Animals↗
Influence of staphylococcal lipoteichoic acid on the frustrated phagocytosis of neutrophils against opsonized corneocytes.
Stratum corneum (SC) exerts a proinflammatory effect in the presence of complement. When Staphylococcus aureus (S. aureus) invades the skin through damaged SC, neutrophils accumulate at the subcorneal portion of epidermis to phagocytize the S. aureus as noted in impetigo. Besides the phagocytosis of bacteria, neutrophils interact with opsonized SC in a form of frustrated phagocytosis, increasing a damage of the surrounding tissues. Based on our previous finding that staphylococcal protein A promotes the interaction between SC and neutrophils, we investigated whether lipoteichoic acid (LTA), another cell wall component of S. aureus, also shows similar properties. We found that LTA significantly promoted the binding of neutrophils to opsonized SC, resulting in an increase in SC-induced respiratory burst of neutrophils assessed by chemiluminescence (CL). The binding of neutrophils to the SC was almost completely inhibited by the blocking of CR3 with anti-CD11b antibody, suggesting that the binding between SC and neutrophils is mediated by interaction between C3bi and CR3 (Mac-1). Such enhanced interaction seems to function in the primary host defence mechanism against the invading S. aureus through the skin such as in impetigo.
Antibodies, Monoclonal↗
The covalent binding reaction of C3 and C4.
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Animals↗
Reduced expression of the functionally active complement receptor for iC3b but not for C3d on an avirulent mutant of Candida albicans.
Pseudohyphae of Candida albicans bear surface receptors for iC3b and C3d. In order to determine a possible role for these receptors in the pathogenesis of candidiasis, a spontaneous C. albicans mutant, m-10, which exhibits reduced ability to adhere in vitro to fibrin platelet clots and epithelial cells or to cause endocarditis in a rabbit model, and its parent wild-type (wt) strain were compared for receptor expression in rosetting assays with sheep erythrocytes carrying iC3b (EAC1423bi) or C3d (EAC1423d). An equally high attachment to wt and m-10 was seen with EAC1423d, whereas rosetting with EAC1423bi was reduced by 53% in m-10 compared with wt. In inhibition studies, rosetting of wt with EAC1423bi was markedly inhibited by culture filtrate, hyphal-cell extract, and DEAE-fractionated material prepared from wt (54, 87, and 70% decreases in rosetting, respectively), thus suggesting the presence of the soluble, functionally active iC3b receptor of C. albicans in each of these preparations. Minimal inhibition of iC3b rosetting, however, was seen with the identical materials from m-10 (21, 5, and 12%, respectively). All of the preparations from the two strains were equally effective in their inhibitory activities against rosetting of C3d. A human serum specimen obtained from a patient with chronic mucocutaneous candidiasis blocked iC3b rosetting of the wt strain almost completely. When used in an immunoblot, this serum recognized proteins of 68 to 71, 55, and 50 kilodaltons (kDa) in hyphal-cell extracts of the wt. With the same preparation of the avirulent mutant, only weak reactions with the 68- to 71-kDa and 55-kDa proteins occurred, while the 50-kDa protein was not detectable. Taken together, these results indicate that the expression of the functionally active iC3b receptor on C. albicans may be involved in the virulence of the organism, possibly by mediating adherence to mammalian cells.
Antigens, Differentiation, B-Lymphocyte↗
Isolation and characterization of cell surface mutants of Candida albicans.
Mutant strains of Candida albicans were obtained by selecting for cells that escaped agglutination by a polyclonal antiserum raised against standard C. albicans serotype A isolate B311. Mutants were obtained from strains B311 and B792 and from four strains isolated from patients with acquired immunodeficiency syndrome. All 15 tested mutants retained characteristic sugar assimilation patterns. All but one of the mutants retained the ability to form germ tubes and chlamydospores. Two mutants from an acquired immunodeficiency syndrome-derived isolate were deficient in binding complement ligands iC3b and C3d, whereas another mutant was deficient in binding ligand iC3b but not C3d. The hyphae of these three mutants lacked antigens when examined by Western immunoblotting with monoclonal antibody Ca-A, which detects several glycoproteins, including C3d-binding proteins. One of the complement-binding-deficient mutants was tested for its ability to colonize the gastrointestinal tract of rabbits but did not differ from the wild-type parent in site or degree of colonization. The proton magnetic resonance spectra of bulk mannan carbohydrate extracted from tested mutants showed the loss of a signal characteristic of the mannosyl alpha-PO4 linkage; each mutant also had a distinct pattern of other changes.
Agglutinins↗
Role of fibrinogen in complement inhibition by streptococcal M protein.
M protein, the major virulence factor of group A streptococci, has antiopsonic activity in that it inhibits activation of the alternative complement pathway on the streptococcal surface. Two properties of M protein have been claimed to account for the inhibitory activity, namely, (i) its binding affinity for complement factor H, which is an inhibitor of alternative pathway activation, and (ii) its high binding affinity for fibrinogen. We have recently shown that fibrinogen, like M protein, inhibits alternative pathway activation by possessing binding affinity for factor H. Here we report that fibrinogen effectively competes with factor H for binding to M protein but retains its own binding affinity for factor H. The presence of fibrinogen did not significantly affect alternative pathway inhibition on the streptococcal surface.
Antigens, Bacterial↗
Complement activation in neonatal infection.
To investigate the usefulness of indices of complement activation in the diagnosis of infections in the neonatal period, activation products C4d, Ba, and C3d were measured in 42 babies with a putative diagnosis of infection based on clinical/laboratory criteria, and compared with conventional clinical and haematological criteria of infection and with C reactive protein. The diagnosis of sepsis was confirmed by culture and identification of organisms in 17. Fourteen babies in whom infection was not suspected formed the control group. In babies with proved infection, concentrations of the fragments C4d, Ba, and C3d were higher than in babies with suspected infection in whom microbiological tests were negative, and concentrations of Ba and C3d were higher than in controls. C reactive protein and the platelet count were not significantly different in babies with proved infection and those with negative microbiological tests, but in the latter, C reactive protein concentrations were higher than in controls. Of the indices studied, high concentrations of Ba predicted microbiologically proved infection with the highest sensitivity (47.1%) and specificity (92.0%). Ba thus seems to be useful as an early indicator of infection in the neonatal period.
Analysis of Variance↗
Relation between synovial fluid C3 degradation products and local joint inflammation in rheumatoid arthritis, osteoarthritis, and crystal associated arthropathy.
C3 degradation products (C3dg/d) were estimated in 288 synovial fluid (SF) samples (rheumatoid arthritis (RA) 93, osteoarthritis (OA) 68, chronic pyrophosphate arthropathy 80, acute pseudogout 20, others 27) from knees of 138 patients (bilateral 67, serial sampling on two to six occasions 40). At each aspiration knees were defined as 'active' or 'inactive' by single observer global assessment using six clinical parameters of inflammation. Lack of correlation between paired SF and plasma C3dg/d implied local C3 activation within joints. Raised SF C3d levels were found in active compared with inactive RA joints (mean (range) 51 (15-105) and 6 (0-15) units/ml respectively). Low SF C3dg/d levels were found in OA (mean (range) 0.8 (0-7) units/ml) and chronic pyrophosphate arthropathy (mean (range) 4 (0-16) units/ml), irrespective of clinical activity. In contrast, very high levels (mean (range) 61 (16-126) units/ml) were present in all cases of pseudogout. These differences remained after correction for SF C3 or albumin. This study is the first to show a positive correlation between SF C3dg/d and local inflammation in RA joints. It further suggests that C3 activation is a constant feature of pseudogout but not an accompaniment of inflammation associated with chronic crystal associated synovitis or OA.
Adult↗
Complement activation and HLA-B27.
The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopolysaccharide treatment (17.6 (3.7)% v 15.0 (3.8)%). The differences occurred irrespective of previous arthritis, complement C4 or Bf phenotype, or variation in background complement levels. The findings suggest that an increased responsiveness to complement activators may contribute to the pathogenesis of HLA-B27 associated inflammatory diseases.
Adult↗
Complement activation by cellulosic dialysis membranes.
AIMS: To assess the effect of cellulosic dialysis membranes on the production of complement degradation products to determine to the role of the classical pathway. METHOD: Complement activation was studied in 33 patients during a single haemodialysis session using cellulosic membranes. Pre- and post-dialysis plasma EDTA valves of C3, C4, C3dg, C4d and C reactive protein (CRP) were measured. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Post-dialysis C4 (p = 0.0003), C3dg (p < 0.0001), and C4d (p = 0.003) concentrations were increased compared with pre-dialysis values. There was no significant change in C3 (p = 0.095) and CRP (p = 0.13) values. Post-dialysis C3dg and C4d concentrations correlated significantly (p = 0.007). IgG, an undialysed molecule, was quantified and post-dialysis valves were significantly higher than those before dialysis (p = 0.0002), indicating a degree of haemoconcentration. To remove this effect, the C3:IgG, C4:IgG, C3dg:IgG, C4d:IgG and CRP:IgG ratios were calculated. Compared with pre-dialysis values, post-dialysis C3dg:IgG and C4d:IgG ratios were increased and C3:IgG decreased significantly. No change was observed in C4:IgG and CRP:IgG ratios. CONCLUSION: This study confirms that significant complement activation takes place following dialysis with cellulosic membranes. This is denoted by an increase in C3dg. This was paralleled by a rise in C4d, implying a contributory role for the classical pathway. Concomitant post-dialysis increases in IgG and C4 indicate a degree of haemoconcentration; but removal of this effect shows that C3dg and C4d are increased following dialysis--suggesting classical, in addition to alternative, pathway activation.
Adult↗
Complement activation profiles in disease.
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Complement Activation↗
Infections and hypocomplementemia.
The complement system, phagocytic leukocytes, and antibodies constitute the "department of defense" in the battle against infections caused by pyogenic microorganisms. Complement components are capable of directly killing (by lysis) certain susceptible bacteria and are the source of chemotactic peptides and heat-labile opsonin, which facilitate recognition and killing of microbes by phagocytic cells. When these vital functions are compromised, as in individuals with inherited deficiencies of complement components, the result is unusual susceptibility to severe infections.
Complement Activation↗
Effects of complement activation by hemodialysis membranes.
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Animals↗
Complement and glomerular disease - a natural history study.
Over a 5-year period we have performed sequential measurements of a range of complement components in 127 patients. Each had a well-characterised glomerular lesion and there was no evidence of an underlying connective tissue disorder. In 17 patients with varied histopathology, who did not have C3 nephritic factor, there was a persisting complement defect which was present during remission in the patients we were able to study. The finding of such defects is consistent with the thesis that primary complement system abnormalities predispose to the development of glomerular lesions. Interestingly, these abnormalities did not influence the prognosis of our patients. In 12 other cases without C3 nephritic factor, complement levels were below the normal range when the glomerular lesion was active but returned to it in remission; these were secondary changes. We showed by discriminant analysis that some circulating complement component levels, assessed in relation to each other and without reference to a statistically derived 'normal' range, discriminated between histological subgroups and had prognostic significance as well. These patterns could not be distinguished until the data were stored and analysed by computer.
Analysis of Variance↗