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On the mechanism of high dose intravenous immunoglubulin (IVIG) action in myasthenia gravis (MG)
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IMMUNOGLOBULIN G (IgG) LOCALIZATION DURINGACUTEAUTOIMMUNE DEMYELINATION G.R. WAYNEMOOREand CEDRIC S. RAINE, Albert Einstein College of Medicine, The Bronx, New York I0461, U.S.A. Immunoglobulin G (IgG) is found in high concentration in the lesions o$ multi p l e sclerosis (MS) and i t s experimental analog, experimental a11ergic encepha l o m y e l i t i s (EAE). The role of IgG in these lesions has been studied by means of immuno-electron microscopy. Acute EAE was induced in Strain i3 guinea pigs by inoculation of whole ~hite matter and complete Freund'~ adjuvant. At the time of onset of signs, animals were perfused with 4,% paraformaldehyde and 5% glutaraldehyde, and lymph node and CNS tissue embedded in epoxy. Thin sections were treated with sodium meta-perlodate, goat anti-guinea pig IgG (Fc fragment) and rabbit anti-goat IgG coupled to c o l l o i d a l gold. Staining of the rough endoplasmlc reticulum and Golgi apparatus of plasma c e l l s was observed in lymph node. In EAE lesions, gold l a b e l l i n g was seen over e x t r a c e l l u l a r electron dense material closely assoclated with processes of macrophages engaged in myelin phagocytosis. In addition, the e x t r a c e l l u l a r aspect of clatrin-coated p i t s on the macrophage surfaces was occasionaily stained. Within macrophages, gold l a b e l l i n g of t i p s of whorls of myelin debris was observed. The results suggest that IgG may serve as a ]igand in the clathrin-coated p i t responsible for receptor-mediated phagocytosis of myelin by macrophages during autoimmune demyelination. bupported by NS 07098, NS 08952, NS Ii92U; and the MS Society of Canada.
ON THE MECHANISM OF HIGH DOSE INTRAVENOUS IMMUNOGLOBULIN (IVIG) ACTION IN MYASTHENIA GP~AVIS (MG) Morel E.*, Liblau R*, Gajdos Ph.*** INSERM U25, CNRSUA122, HoRital Necker, Paris, France. ** Clinique de R6animation, Hopital R. Poincar~, Garches, France Previous studies on MG patients have shown that high intravenous immunoglobulin doses could be a method of short-term treatment in the acute form of MGwith increase of clinical score and decrease of anti-acetylcholine receptor (anti-AChR) antibody t i t e r about 70% of the patients. The mechanism of IVIG (veinoglobulineR, Institut M6rieux) (Vg) action was studied by estimating their effect on anti-AChR formation. Kinetic studies were made using different doses of Vg at different stages of the formation of the complex between the MG sera and the AChR solubilized from human muscle. Sera from MGpatients with various clinical status and with positive anti-AChR antibodies were used. No interference was observed between the Vg (125 mg/l) and the formation of the ~bungarotoxin-AChR complex nor in the anti-AChR antibody t i t e r determination. On the contrary, diminution of the anti-AChR antibody t i t e r (lO to 30%) was shown for most of the sera when the Vg were added during incubation of the MG sera with the ~bungarotoxin-AChR-complexes. Dose-dependent and time-dependent curves were established. This partial suppression of anti-AChR antibody formation could be due to dissolution of antibody-AChR complexes by immunoglobulin excess or to the presence of anti-idiotypic a c t i v i t y in the Vg preparation.
IMMUNOGLOBULIN G (IgG) LOCALIZATION DURINGACUTEAUTOIMMUNE DEMYELINATION G.R. WAYNEMOOREand CEDRIC S. RAINE, Albert Einstein College of Medicine, The Bronx, New York I0461, U.S.A. Immunoglobulin G (IgG) is found in high concentration in the lesions o$ multi p l e sclerosis (MS) and i t s experimental analog, experimental a11ergic encepha l o m y e l i t i s (EAE). The role of IgG in these lesions has been studied by means of immuno-electron microscopy. Acute EAE was induced in Strain i3 guinea pigs by inoculation of whole ~hite matter and complete Freund'~ adjuvant. At the time of onset of signs, animals were perfused with 4,% paraformaldehyde and 5% glutaraldehyde, and lymph node and CNS tissue embedded in epoxy. Thin sections were treated with sodium meta-perlodate, goat anti-guinea pig IgG (Fc fragment) and rabbit anti-goat IgG coupled to c o l l o i d a l gold. Staining of the rough endoplasmlc reticulum and Golgi apparatus of plasma c e l l s was observed in lymph node. In EAE lesions, gold l a b e l l i n g was seen over e x t r a c e l l u l a r electron dense material closely assoclated with processes of macrophages engaged in myelin phagocytosis. In addition, the e x t r a c e l l u l a r aspect of clatrin-coated p i t s on the macrophage surfaces was occasionaily stained. Within macrophages, gold l a b e l l i n g of t i p s of whorls of myelin debris was observed. The results suggest that IgG may serve as a ]igand in the clathrin-coated p i t responsible for receptor-mediated phagocytosis of myelin by macrophages during autoimmune demyelination. bupported by NS 07098, NS 08952, NS Ii92U; and the MS Society of Canada.
ON THE MECHANISM OF HIGH DOSE INTRAVENOUS IMMUNOGLOBULIN (IVIG) ACTION IN MYASTHENIA GP~AVIS (MG) Morel E.*, Liblau R*, Gajdos Ph.*** INSERM U25, CNRSUA122, HoRital Necker, Paris, France. ** Clinique de R6animation, Hopital R. Poincar~, Garches, France Previous studies on MG patients have shown that high intravenous immunoglobulin doses could be a method of short-term treatment in the acute form of MGwith increase of clinical score and decrease of anti-acetylcholine receptor (anti-AChR) antibody t i t e r about 70% of the patients. The mechanism of IVIG (veinoglobulineR, Institut M6rieux) (Vg) action was studied by estimating their effect on anti-AChR formation. Kinetic studies were made using different doses of Vg at different stages of the formation of the complex between the MG sera and the AChR solubilized from human muscle. Sera from MGpatients with various clinical status and with positive anti-AChR antibodies were used. No interference was observed between the Vg (125 mg/l) and the formation of the ~bungarotoxin-AChR complex nor in the anti-AChR antibody t i t e r determination. On the contrary, diminution of the anti-AChR antibody t i t e r (lO to 30%) was shown for most of the sera when the Vg were added during incubation of the MG sera with the ~bungarotoxin-AChR-complexes. Dose-dependent and time-dependent curves were established. This partial suppression of anti-AChR antibody formation could be due to dissolution of antibody-AChR complexes by immunoglobulin excess or to the presence of anti-idiotypic a c t i v i t y in the Vg preparation.