[Specific measurement of alternate pathway activation of complement in human glomerulonephritides (GN): 125 cases (author's transl)]

International audienceC3 cleaving activity through alternate pathway, appreciated by native C3 antigen reduction in the presence of Mg EGTA, has been measured in sera of 40 controls and of 125 GN patients. The normal percentage of native C3 conversion ranged from 0 to 29 in controls (p less than 0.05). The number of positive samples is 0/30 in lupus GN (0%), 13/29 in acute GN (45%) and 26/66 in membranoproliferative GN (39%) with 7/8 in dense deposits subtype. The presence of alternate pathway activators of complement correlated with serum C3 level: their frequency is respectively 0, 0.32, and 0.48 if serum C3 is normal, low, and very low. Such activity correlated also well with alternate pathway C3 activation (low C3 and normal C4): the frequency of positive samples is respectively 0, 0.07, and 0.51 in the presence of No C3 activation, classical pathway activation (low C3 and low C4), and alternate pathway activation. The nature of such serum activators could be nephritic factor, bacterial polysaccharides, polymeric IgA, activated properdin, peculiar immune complexes, or other factors. Such measurement is an improvement immunopathological step in the investigation of human GN.C3 cleaving activity through alternate pathway, appreciated by native C3 antigen reduction in the presence of Mg EGTA, has been measured in sera of 40 controls and of 125 GN patients. The normal percentage of native C3 conversion ranged from 0 to 29 in controls (p less than 0.05). The number of positive samples is 0/30 in lupus GN (0%), 13/29 in acute GN (45%) and 26/66 in membranoproliferative GN (39%) with 7/8 in dense deposits subtype. The presence of alternate pathway activators of complement correlated with serum C3 level: their frequency is respectively 0, 0.32, and 0.48 if serum C3 is normal, low, and very low. Such activity correlated also well with alternate pathway C3 activation (low C3 and normal C4): the frequency of positive samples is respectively 0, 0.07, and 0.51 in the presence of No C3 activation, classical pathway activation (low C3 and low C4), and alternate pathway activation. The nature of such serum activators could be nephritic factor, bacterial polysaccharides, polymeric IgA, activated properdin, peculiar immune complexes, or other factors. Such measurement is an improvement immunopathological step in the investigation of human GN

[Anticomplement activity of a polyanion: pentosan sulfuric polyester. III. Mechanism of functional inactivation of the different properdin and complement system fractions]

International audienceIn vitro, the drug pentosan-poly-sulfoester (PPS) changes the electrophoretic migration of different proteins from the complement and properdin systems, such as native C3 (beta 1C globulin), C3c (beta-1A globulin), C3d (alpha-2D globulin), C1s inactivator (ClsINA), Clq and properdin factor B (B). Their more anodal migration is the consequence of a molecular alteration and persists after prolonged dialysis. These structural changes, yet undefined, explain the loss of functional activity of these proteins, and the anticomplementary activity of this drug. Moreover, PPS is able to block the alternate pathway activation by its action on properdin factor B (C3 proactivator). In fact, in presence of PPS, the activators of the properdin systems such as C3 nephritic factor are inactive. These altered mobilities are also responsible for the overestimation in the antigenic concentration of B (+ 45%), C4 (+27%) and C3/C3c (+ 14%), found in human serum containing 50 mg/ml of PPS. PPS has an original action upon the complement and properdin systems, which allows its clinical use as a potent inhibitor of the humoral mediators of inflammation.In vitro, the drug pentosan-poly-sulfoester (PPS) changes the electrophoretic migration of different proteins from the complement and properdin systems, such as native C3 (beta 1C globulin), C3c (beta-1A globulin), C3d (alpha-2D globulin), C1s inactivator (ClsINA), Clq and properdin factor B (B). Their more anodal migration is the consequence of a molecular alteration and persists after prolonged dialysis. These structural changes, yet undefined, explain the loss of functional activity of these proteins, and the anticomplementary activity of this drug. Moreover, PPS is able to block the alternate pathway activation by its action on properdin factor B (C3 proactivator). In fact, in presence of PPS, the activators of the properdin systems such as C3 nephritic factor are inactive. These altered mobilities are also responsible for the overestimation in the antigenic concentration of B (+ 45%), C4 (+27%) and C3/C3c (+ 14%), found in human serum containing 50 mg/ml of PPS. PPS has an original action upon the complement and properdin systems, which allows its clinical use as a potent inhibitor of the humoral mediators of inflammation

[Anticomplementary activity of a polyanion: polyanion: pentosan-poly-sulfoester. I. "In vitro" study and "in vivo" trial in human glomerulonephritis (author's transl)]

International audienceThe drug, pentosan-poly-sulfoester (PPS), has an anticomplementary activity (ACA) on human serum both in vitro and in vivo, as judged by a reduction in total hemolytic complement activity (CH 50). In vitro, this ACA is very potent, immediate and temperature independent. In vivo this ACA obtained with a IV dose of 100 mg per 8 hours eg 300 mg/24 h, increases with the duration of treatment (mean time:30 days), suggesting a cumulative effect. Eleven patients with glomerulonephritis (GN) received such a treatment (8 with acute post-streptococcal GN and 3 with mesangio-proliferative GN). In patients with already marked hypocomplementemia, the ACA is difficult to establish, while in patients with normal complement activity or moderate hypocomplementemia, the decrease of CH 50 level in serum is obvious. There was no significant change inthe serum level of C3, C4, properdin factor B as measured by radial immunodiffusion technique. The clinical course of these GN was apparently not affected by this treatment. Neverthless, the in vivo ACA of PPS is firmly established and we can speculate that this functional depletion in complement may prevent or decrease the liberation of humoral mediators of inflammation.The drug, pentosan-poly-sulfoester (PPS), has an anticomplementary activity (ACA) on human serum both in vitro and in vivo, as judged by a reduction in total hemolytic complement activity (CH 50). In vitro, this ACA is very potent, immediate and temperature independent. In vivo this ACA obtained with a IV dose of 100 mg per 8 hours eg 300 mg/24 h, increases with the duration of treatment (mean time:30 days), suggesting a cumulative effect. Eleven patients with glomerulonephritis (GN) received such a treatment (8 with acute post-streptococcal GN and 3 with mesangio-proliferative GN). In patients with already marked hypocomplementemia, the ACA is difficult to establish, while in patients with normal complement activity or moderate hypocomplementemia, the decrease of CH 50 level in serum is obvious. There was no significant change inthe serum level of C3, C4, properdin factor B as measured by radial immunodiffusion technique. The clinical course of these GN was apparently not affected by this treatment. Neverthless, the in vivo ACA of PPS is firmly established and we can speculate that this functional depletion in complement may prevent or decrease the liberation of humoral mediators of inflammation

Human glomerulonephritis and the C3 nephritic factor (C3NeF).

International audiencexx

Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients

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