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Clark D West - One of the best experts on this subject based on the ideXlab platform.
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dependence of the Nephritic Factor reaction on properdin Factor b
2017Co-Authors: Edward J Ruley, Judith Forristal, Neil C Davis, Cynthia Andres, Clark D WestAbstract:A B S T R A C T Membranoproliferative nephritis in children is frequently associated with a hypocomplementemia produced at least in part by C3 breakdown mediated by a circulating anticomplementary Factor known as C3 Nephritic Factor (C3NeF). C3 breakdown by this Factor in vitro requires the presence of a pseudoglobulin coFactor and magnesium. The present study provides evidence that properdin Factor B (C3 proactivator) is activated in the Nephritic Factor reaction and is the
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Nephritic Factor and recurrence in the renal transplant of membranoproliferative glomerulonephritis type ii
Pediatric Nephrology, 2008Co-Authors: Clark D West, John J BisslerAbstract:Animal models suggest a role for Nephritic Factor in the pathogenesis of glomerular disease, but evidence for a role in human disease is lacking. To assess its role, we applied a recently developed method that allows measurement of low levels of Nephritic Factor activity to stored serum specimens from three patients who had membranoproliferative glomerulonephritis (MPGN) type II. All three had had renal transplants, and one lost two of three transplants from recurrent disease. Evidence for a role for Nephritic Factor in human disease was a positive correlation between the level of Nephritic Factor activity and both the severity of recurrence and an increase in serum creatinine concentration. However, the hypocomplementemia was never severe; C3 levels of 49–76 mg/dl and Nephritic Factor levels of 89 U/ml were associated with severe recurrences. We have previously seen severe disease with mild hypocomplementemia. In contrast, patients with partial lipodystrophy often have severe hypocomplementemia and, presumably, high levels of Nephritic Factor yet have a mild glomerulonephritis. Disease severity and Nephritic Factor levels thus appear to be inversely related. The disease is progressive when only moderate amounts of Nephritic Factor have been circulating and C3 only mildly depressed.
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a hemolytic method for the measurement of Nephritic Factor
Journal of Immunological Methods, 2008Co-Authors: Clark D WestAbstract:The absence of a simple and widely applicable test for the measurement of NF activity has hampered the accumulation of evidence bearing on its nephritogenicity. The extensive modification of a screening test for this autoantibody, reported here, has increased the range and precision of the test and made it less laborious. C3b deposited on sheep E by the reaction of NF with NHS forms a C5 convertase which, with addition of rat EDTA serum, leads to hemolysis of the cells proportionate under the right conditions to the concentration of NF in the reaction mixture. The calibration line is straight or slightly concave and passes through the origin. The method detects the activity of both the NF of the amplification loop, NFa, found in MPGN type II, and the NF of the terminal pathway, NFt, found in MPGN types I and III. Interday coefficients of variation ranged from 6.6% to 13.5% and intraday from 7.0% to 12.6%. Although serum C3 levels can be markedly depressed when NF levels are high, C3 levels and NF activity generally correlate poorly. The C3 level could be low and NF absent or, occasionally, NF present with the C3 level normal. NF activity was absent from the stored serum of patients with active SLE, AGN or with an IgA nephropathy.
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research paper a hemolytic method for the measurement of Nephritic Factor
2008Co-Authors: Clark D WestAbstract:The absence of a simple and widely applicable test for the measurement of NF activity has hampered the accumulation of evidence bearing on its nephritogenicity. The extensive modification of a screening test for this autoantibody, reported here, has increased the range and precision of the test and made it less laborious. C3b deposited on sheep E by the reaction of NF with NHS forms a C5 convertase which, with addition of rat EDTA serum, leads to hemolysis of the cells proportionate under the right conditions to the concentration of NF in the reaction mixture. The calibration line is straight or slightly concave and passes through the origin. The method detects the activity of both the NF of the amplification loop, NFa, found in MPGN type II, and the NF of the terminal pathway, NFt, found in MPGN types I and III. Interday coefficients of variation ranged from 6.6% to 13.5% and intraday from 7.0% to 12.6%. Although serum C3 levels can be markedly depressed when NF levels are high, C3 levels and NF activity generally correlate poorly. The C3 level could be low and NF absent or, occasionally, NF present with the C3 level normal. NF activity was absent from the stored serum of patients with active SLE, AGN or with an IgA nephropathy. © 2008 Published by Elsevier B.V.
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composition of Nephritic Factor ndash generated glomerular deposits in membranoproliferative glomerulonephritis type 2
American Journal of Kidney Diseases, 2001Co-Authors: Clark D West, David P Witte, James A McadamsAbstract:Abstract Two observations suggest that Nephritic Factors (NFs) may be nephritogenic. First, glomerulonephritis is present in unusual frequency in three conditions in which the function of Factor H is blocked, a dysfunction also produced by NFs. Second, in membranoproliferative glomerulonephritis (MPGN) type 2, subepithelial deposits on the paramesangial portion of the glomerular basement membrane are found only in renal biopsy specimens obtained during hypocomplementemia when NF is presumably present. In the present study, the composition of these deposits with respect to C3 derivatives was assessed by immunohistological evaluation using anti-C3c and anti-C3d. The assessment used routinely obtained photomicrographs, as well as immunohistologic examination of freshly cut tissue using the double-antibody method. Deposits in patients with typical hypocomplementemic MPGN type 2 reacted only with anti-C3c, whereas those in two patients with rapidly progressive MPGN type 2, six patients with poststreptococcal acute glomerulonephritis, and five patients with juvenile acute nonproliferative glomerulitis reacted with anti-C3d, as well as anti-C3c. Because all products derived from the breakdown of C3 except C3c react with anti-C3d, the deposits in typical MPGN type 2 must be composed only of C3c. With complete breakdown of bound C3b, C3c is released into the fluid phase. Therefore, the C3c in the deposits cannot be a product of a glomerular complement reaction, but instead must be formed in the circulation by the reaction of NF with native C3. Supporting C3c as the only constituent of these deposits is the observation that they are devoid of properdin and C5 is present in only small amounts.
Margarita Lopeztrascasa - One of the best experts on this subject based on the ideXlab platform.
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requirements for the production of high titre c3 Nephritic Factor nef antibody in vitro
Immunology, 1992Co-Authors: M A Marin, G Fontan, Margarita LopeztrascasaAbstract:C3 Nephritic Factor (NEF) is an IgG autoantibody directed against neoantigenic determinants of the alternative C3 convertase (C3b.Bb). Structural and functional studies require important amounts of this antibody, which are difficult to obtain from patients' sera. We have developed a method for increasing NEF production in vitro. Epstein-Barr virus is a herpes virus which transforms B lymphocytes. Some authors were able to induce the production of NEF in vitro after infection with Epstein-Barr virus (EBV). These works were preformed without any previous cellular selection of B cells. We have performed a method of preselecting antigen-binding cells prior to EBV transformation. Non-preselected cells yielded 0.16 U/million cells in culture (U/M) of NEF antibody, whereas enriched cells for NEF antibody in eliminated 8 U/M (sheep erythrocytes coated with anti-IgG, A, M). Specific NEF synthesis can be increased, in peripheral blood mononuclear cells (PBMC) from patients by in vitro stimulation with the antigens recognized by NEF [C3b.Bb, 21,000 MW protein from patients' E membranes and 26,000 MW protein from sheep E membranes (ShE)]. The highest stimulation is induced by the C3b.Bb and by 26,000 MW protein, 21,000 MW protein had lowest stimulatory effect. In this work also we have shown that patients having NEF antibody in sera have an increase of the CD5-CD19 subset, when compared with the controls.
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familial incidence of c3 Nephritic Factor
Nephron, 1991Co-Authors: Margarita Lopeztrascasa, J M Martinvilla, Jose L Vicario, M A Marin, Jorge Martinezara, M C Garciamesseguer, A Arnaizvillena, G FontanAbstract:C3 Nephritic Factor (NEF) has been found in 3 siblings presenting different (or none) degrees of renal disease. Other relatives, including their dead father, suffered from a renal illness. In 2 of the siblings, NEF activity was restricted to IgG1 and IgG3 subclasses. Familial NEF incidence and a shared C3 allotype and a common HLA haplotype including BfS alleles for the 3 NEF-positive siblings suggest that at least in our cases genetical Factors may be involved in NEF generation.
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interaction of c3 Nephritic Factor nef with erythrocyte membranes complement independent binding to sheep and patients erythrocytes
Molecular Immunology, 1991Co-Authors: M A Marin, G Fontan, Margarita LopeztrascasaAbstract: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.
M A Marin - One of the best experts on this subject based on the ideXlab platform.
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requirements for the production of high titre c3 Nephritic Factor nef antibody in vitro
Immunology, 1992Co-Authors: M A Marin, G Fontan, Margarita LopeztrascasaAbstract:C3 Nephritic Factor (NEF) is an IgG autoantibody directed against neoantigenic determinants of the alternative C3 convertase (C3b.Bb). Structural and functional studies require important amounts of this antibody, which are difficult to obtain from patients' sera. We have developed a method for increasing NEF production in vitro. Epstein-Barr virus is a herpes virus which transforms B lymphocytes. Some authors were able to induce the production of NEF in vitro after infection with Epstein-Barr virus (EBV). These works were preformed without any previous cellular selection of B cells. We have performed a method of preselecting antigen-binding cells prior to EBV transformation. Non-preselected cells yielded 0.16 U/million cells in culture (U/M) of NEF antibody, whereas enriched cells for NEF antibody in eliminated 8 U/M (sheep erythrocytes coated with anti-IgG, A, M). Specific NEF synthesis can be increased, in peripheral blood mononuclear cells (PBMC) from patients by in vitro stimulation with the antigens recognized by NEF [C3b.Bb, 21,000 MW protein from patients' E membranes and 26,000 MW protein from sheep E membranes (ShE)]. The highest stimulation is induced by the C3b.Bb and by 26,000 MW protein, 21,000 MW protein had lowest stimulatory effect. In this work also we have shown that patients having NEF antibody in sera have an increase of the CD5-CD19 subset, when compared with the controls.
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familial incidence of c3 Nephritic Factor
Nephron, 1991Co-Authors: Margarita Lopeztrascasa, J M Martinvilla, Jose L Vicario, M A Marin, Jorge Martinezara, M C Garciamesseguer, A Arnaizvillena, G FontanAbstract:C3 Nephritic Factor (NEF) has been found in 3 siblings presenting different (or none) degrees of renal disease. Other relatives, including their dead father, suffered from a renal illness. In 2 of the siblings, NEF activity was restricted to IgG1 and IgG3 subclasses. Familial NEF incidence and a shared C3 allotype and a common HLA haplotype including BfS alleles for the 3 NEF-positive siblings suggest that at least in our cases genetical Factors may be involved in NEF generation.
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interaction of c3 Nephritic Factor nef with erythrocyte membranes complement independent binding to sheep and patients erythrocytes
Molecular Immunology, 1991Co-Authors: M A Marin, G Fontan, Margarita LopeztrascasaAbstract: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.
Alexandra Dumfarth - One of the best experts on this subject based on the ideXlab platform.
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c4 Nephritic Factor in patients with immune complex mediated membranoproliferative glomerulonephritis and c3 glomerulopathy
Orphanet Journal of Rare Diseases, 2019Co-Authors: Nora Garam, Zoltan Prohaszka, Agnes Szilagyi, Christof Aigner, Alice Schmidt, Martina Gaggl, Gere Sunderplassmann, Dora Bajcsi, Jurgen Brunner, Alexandra DumfarthAbstract:Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4Nephritic Factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic Factors. One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 Nephritic Factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of Nephritic Factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.
G Fontan - One of the best experts on this subject based on the ideXlab platform.
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requirements for the production of high titre c3 Nephritic Factor nef antibody in vitro
Immunology, 1992Co-Authors: M A Marin, G Fontan, Margarita LopeztrascasaAbstract:C3 Nephritic Factor (NEF) is an IgG autoantibody directed against neoantigenic determinants of the alternative C3 convertase (C3b.Bb). Structural and functional studies require important amounts of this antibody, which are difficult to obtain from patients' sera. We have developed a method for increasing NEF production in vitro. Epstein-Barr virus is a herpes virus which transforms B lymphocytes. Some authors were able to induce the production of NEF in vitro after infection with Epstein-Barr virus (EBV). These works were preformed without any previous cellular selection of B cells. We have performed a method of preselecting antigen-binding cells prior to EBV transformation. Non-preselected cells yielded 0.16 U/million cells in culture (U/M) of NEF antibody, whereas enriched cells for NEF antibody in eliminated 8 U/M (sheep erythrocytes coated with anti-IgG, A, M). Specific NEF synthesis can be increased, in peripheral blood mononuclear cells (PBMC) from patients by in vitro stimulation with the antigens recognized by NEF [C3b.Bb, 21,000 MW protein from patients' E membranes and 26,000 MW protein from sheep E membranes (ShE)]. The highest stimulation is induced by the C3b.Bb and by 26,000 MW protein, 21,000 MW protein had lowest stimulatory effect. In this work also we have shown that patients having NEF antibody in sera have an increase of the CD5-CD19 subset, when compared with the controls.
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familial incidence of c3 Nephritic Factor
Nephron, 1991Co-Authors: Margarita Lopeztrascasa, J M Martinvilla, Jose L Vicario, M A Marin, Jorge Martinezara, M C Garciamesseguer, A Arnaizvillena, G FontanAbstract:C3 Nephritic Factor (NEF) has been found in 3 siblings presenting different (or none) degrees of renal disease. Other relatives, including their dead father, suffered from a renal illness. In 2 of the siblings, NEF activity was restricted to IgG1 and IgG3 subclasses. Familial NEF incidence and a shared C3 allotype and a common HLA haplotype including BfS alleles for the 3 NEF-positive siblings suggest that at least in our cases genetical Factors may be involved in NEF generation.
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interaction of c3 Nephritic Factor nef with erythrocyte membranes complement independent binding to sheep and patients erythrocytes
Molecular Immunology, 1991Co-Authors: M A Marin, G Fontan, Margarita LopeztrascasaAbstract: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.