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Results for “Complement C3 Nephritic Factor”

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At least 127 records · Page 7Linked to original sources
PubMed1979

Activation of the classical pathway of complement by the C3NeF-stabilized cell-bound amplification convertase.

C3 nephritic factor (C3NeF) has been shown to be composed of two heavy and two light chains, like IgG; in addition it shares antigenic determinants with IgG. C3NeF, purified from the sera of eight patients by incorporation of C3NeF into the stabilized fluid phase amplification C3 convertase, C3bBb(C3NeF), followed by its release after decay of convertase function, was investigated for its ability to bind 125I-C1q and to activate 125I-C1. It was found that although fluid phase C3b,Bb(C3NeF) is fully capable of binding 125I-C1q, it is not able to activate 125I-C1 even at concentrations of 1.3 x 10(12) C3bBb(C3NeF) complexs/ml. On the other hand, cell-bound C3bBb(C3NeF) is capable of both binding 125I-C1q and activating 125I-C1. This discrepancy between fluid phase and cell-bound, C3bBb(C3NeF) was found for C3NeF preparations from eight different patients and therefore seems to apply to all C3NeF preparations.

Binding Sites↗
PubMed1990

Familial incidence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomerulonephritis.

C3 nephritic factor is an IgG autoantibody that causes complement activation by stabilizing the alternative pathway C3 convertase. It is associated with partial lipodystrophy and membrano-proliferative glomerulonephritis. The occurrence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomerulonephritis, whether singly or in any combination, is usually sporadic. We describe the coexistence of all three of these conditions in members spanning two generations of a single family. This suggests that the pathogenesis of these conditions may be linked and that genetically determined factors may, in some circumstances, contribute to disease susceptibility.

Biopsy↗
PubMed1984

C3 nephritic factor in a patient with recurrent Neisseria meningitidis infections.

A 15-year-old female experienced two systemic infections with N.meningitidis (group C and B) within a two months period. Classical as well as alternative pathway CH50 determinations on the patients serum showed no lysis. All individual complement factor concentrations, except for C3, were found to be within the reference area. Crossed immunoelectrophoretic analysis of C3 revealed no demonstrable native C3. The patient had normal levels of C3c and a markedly elevated C3d concentration. Serum from the patient was found to convert all native C3 in normal sera within 10 minutes at 37 degrees C. The active converting principle, present in the IgG fraction activated C3 in C4-depleted serum, and had a dose dependent stabilizing effect on the EA-C3bBb complex. The isolated factor showing the characteristics of C3 nephritic factor (C3 NeF), was unchanged in the patients serum over a ten months observation period. Circulating immune complexes (IC) could not be demonstrated by a C1q-dependent assay but the patients capacity to solubilize preformed IC in vitro was virtually abolished. The patient had no signs of renal disease or lipodystrophy.

Adolescent↗
PubMed1982

Increased enzymatic activity of the alternative pathway convertase when bound to the erythrocytes of paroxysmal nocturnal hemoglobinuria.

To investigate the greater fixation of C3 to the erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH) upon activation of complement, we have examined the formation and the reaction of the C3 nephritic factor-stabilized alternative pathway convertase made with purified components on normal and PNH erythrocytes. Each convertase complex converts four to five times more fluid-phase C3 to C3b when affixed to a PNH cell than when affixed to a normal cell. The greater activity of the convertase on PNH cells is not due to differences in the intrinsic or extrinsic stability of the convertase complex. The excessive binding of C3 to PNH cell si due to this increased conversion of fluid-phase C3, because the efficiency of binding of nascent C3b was identical for the two cell types. This is the first instance in which the enzyme activity of a complement complex has been shown to be increased by being affixed to an abnormal surface.

Complement Activating Enzymes↗
PubMedDate not supplied

Interaction of C3 nephritic factor (NEF) with erythrocyte membranes complement-independent binding to sheep and patients' erythrocytes.

Complement-independent binding of C3 nephritic factor (NEF) to sheep erythrocytes was observed in heat-inactivated sera from patients having this autoantibody. The binding was observed after neuraminidase treatment of erythrocytes but not following trypsin treatment. Purified IgG from patients' sera was able to bind to ShE membranes. Binding to rat and rabbit erythrocytes was also observed but not to human group O+ erythrocytes. By Western blot NEF ab recognizes a 26 kD protein on the sheep erythrocytes and a 21 kD protein on human erythrocytes. NEF activity decreased at these positions when blotted nitrocellulose was incubated with NEF antibody. This autoantibody binds human erythrocytes membranes from patients but not from 55 normal blood donors. IgG from a pool from 10 different controls did not bind membrane E from the patients. The amino acid analysis of the 21 kD protein of the patients showed differences in basic residues (Arg and Lys) when compared with the 21 kD protein obtained from controls. N-terminal sequence analysis indicated that it is blocked in both proteins.

Amino Acids↗
PubMed1984

Protection of the classical and alternative complement pathway C3 convertases, stabilized by nephritic factors, from decay by the human C3b receptor.

Formation and function of the classical (C4b,2a) and alternative (C3b,Bb) complement pathway C3 convertases are regulated by the intrinsic lability of the enzymes, extrinsic decay by C4bp and H, cleavage of C4b and C3b by I, and by the inhibitory action of the C3b receptor molecule (CR1). Binding of C4 nephritic factor (C4Nef) to C4b and of C3 nephritic factor (C3Nef) to C3b stabilizes the C3 convertases and bypasses inactivation by C4bp, H and/or I. In the present study, binding of C4Nef to the classical C3 convertase was found to prevent decay of C4b,2a by inputs of CR1 that were at least 15 times the amount of CR1 which inactivated 50% unstabilized classical pathway C3 convertase sites in 2.5 min. CR1 could however inhibit lysis of C4b,2a(C4Nef)-bearing cells in a dose-dependent manner. The latter inhibitory effect was directed at the interaction of C5 with the C5 convertase, most likely at C5 binding to cell-bound C3b. In an analogous manner to C4Nef in the classical pathway, stabilization of alternative pathway C3b,Bb convertase sites by C3Nef resulted in a relative protection of C3 convertase sites from decay by CR1. Thus, C4Nef and C3Nef can bypass all mechanisms susceptible to regulate function of the classical and alternative pathway C3 convertases. Because CR1 is essential for degradation of C3b bound to immune complexes in whole blood, stabilization of C4b,2a and C3b,Bb by C4Nef and C3Nef may alter in vivo processing of immune complexes in patients with nephritic factors.

Complement Activating Enzymes↗
PubMed1990

Evidence that production of autoantibody to the alternative pathway C3 convertase is a normal physiologic event.

The origin of autoantibody production was studied with the use of antibody to the alternative pathway C3 convertase (C3 nephritic factor (C3NeF), as a model. Pokeweed mitogen stimulation of peripheral mononuclear cells from newborn infants, normal adults, and patients with membranoproliferative glomerulonephritis indicated that the ability to make C3NeF is apparently present in everyone from the time of birth. In addition, C3NeF appeared to express a single or very limited idiotope (21/21 isolates). The data also suggest that the elaboration of C3NeF may approximate an antibody response after immunization. Thus the C3NeF fraction of the total IgG or IgM produced in culture by pokeweed mitogen-stimulated mononuclear cells from normal neonates and adults, as well as from patients, was in the range of the production of specific antibody. Further, both IgG and IgM C3NeF produced by cells from these normal individuals, including newborn infants, had an affinity for antigen (10(8) to 10(9) L/mol) that was also in the range of specific antibody. Most of the autoantibody molecules (5/7) from serum were IgG3; two B cell clones producing C3NeF were CD5-negative. These experiments indicate that unmutated germline genes are used in the production of C3NeF and that a limited spectrum of antiidiotypic antibodies regulate its production.

Adult↗
PubMed1984

Factor I deficiency and C3 nephritic factor: immunochemical findings and association with Neisseria meningitidis infection in two patients.

The complement system was examined in two patients with systemic Neisseria meningitidis infections, both of whom had reduced or nondetectable CH50 as analysed by both pathways. C3 measured by conventional technique revealed 19% anti-C3c-reactive protein in the plasma of patient 1 and 3% in patient 2. Patient 1 had circulating C3b but no detectable C3c, C3d, or C4d, whereas patient 2 had normal levels of C3c and C4d and strongly elevated levels of C3d. Factor B analysis revealed no demonstrable native factor B and small amounts of Bb in patient 1 and normal concentration of native factor B plus trace amounts of Bb in patient 2. The depletion of C3 in both patients was due to uncontrolled activation caused by complete factor I deficiency (patient 1) and circulating C3 nephritic factor (patient 2). Both parents of patient 1 had factor I concentrations below (mean-2 SD) that seen in normal healthy individuals (n = 20). Circulating immune complexes (IC) were demonstrated in patient 1 only, whereas serum from both patients had strongly reduced capacity to solubilize preformed IC.

Adolescent↗