High-Dose Intravenous Gammaglobulin for Myasthenia Gravis

Gajdos, P; Outin, Hervé; Elkharrat, D.; Brunel, D; Rohan-Chabot, P. de; Raphael, J. C.; Goulon, M; Goulon‐Goeau, Catherine; Morel, E.

doi:10.1016/s0140-6736(84)90469-0

Cited by 160 publications

(63 citation statements)

References 4 publications

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“…1,2,8,[21][22][23][24][25][26][27][28][29] IVIG is inherently a preparation of polyclonal antibodies representing a multitude of specificities. Preparations of human IgG containing high titers of polyclonal anti-D have been used as an alternative for IVIG in D-positive patients with ITP.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG

Song

Crow

Freedman

et al. 2003

Blood

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Intravenous immunoglobulin (IVIG) is used to treat immune thrombocytopenia resulting from a variety of autoimmune and nonautoimmune diseases such as idiopathic thrombocytopenic purpura (ITP), heparin-induced thrombocytopenia, and posttransfusion purpura. IVIG is a limited resource and although considered safe, may nevertheless carry some risk of transferring disease. Its high cost makes monoclonal antibodies, capable of mimicking the clinical effects of IVIG, highly desirable. We show here, using a murine model of ITP, that selected monoclonal antibodies can protect against thrombocytopenia. SCID mice were pretreated with 1 of 21 monoclonal antibodies before induction of thrombocytopenia by antiplatelet antibody. Four antibodies reacted with the CD24 antigen on erythrocytes. Two antibodies were of the IgM class, and although one IgM antibody caused a minimal degree of anemia (P <.05), neither antibody ameliorated immune thrombocytopenia. One of 2 anti-CD24 antibodies of the IgG class ameliorated immune thrombocytopenia and blocked reticuloendothelial system function at the same doses that protected against thrombocytopenia. Some antibodies reactive with other circulating cell types also protected against immune-mediated thrombocytopenia while no antibody without a distinct target antigen in the mice was protective. Protective monoclonal antibodies significantly prevented thrombocytopenia at down to a 1000-fold lower dose (200 microg/kg) as compared with standard IVIG treatment (2 g/kg). It is concluded that monoclonal IgG with specificity for a circulating cellular target antigen may provide an alternative therapeutic approach to treating immune thrombocytopenia.

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Section: Discussionmentioning

confidence: 99%

Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG

Song

Crow

Freedman

et al. 2003

Blood

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“…However, long-term treatment with these drugs may cause many dose-related adverse effects (24). Intravenous Ig (IVIG) has been shown to be effective for the treatment of a variety of immune-mediated inflammatory diseases (25), including autoimmune cytopenias, GuillainBarré syndrome, multiple sclerosis, myasthenia gravis, anti-factor VIII autoimmune disease, dermatomyositis, Kawasaki disease, vasculitis, uveitis, and graft-versus-host disease (26)(27)(28)(29)(30)(31)(32). Recently, IVIG has also been reported to treat a small group of patients with human autoimmune blistering diseases, including pemphigus and pemphigoid (33,34).…”

Section: Introductionmentioning

confidence: 99%

Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases

Zhao²,

Hilario-Vargas³

et al. 2005

Journal of Clinical Investigation

229

189

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Numerous mechanisms of action have been proposed for intravenous Ig (IVIG). In this study, we used IgG passive transfer murine models of bullous pemphigoid (BP), pemphigus foliaceus (PF), and pemphigus vulgaris (PV) to test the hypothesis that the effect of IVIG in autoantibody-mediated cutaneous bullous diseases is to accelerate the degradation of pathogenic IgG by saturation of the MHC-like Fc receptor neonatal Fc receptor (FcRn). BP, PF, and PV are organ-specific antibody-mediated diseases in which autoantibodies target the hemidesmosomal antigen BP180 and desmosomal antigens Dsg1 and Dsg3, respectively. Antibodies against BP180, Dsg1, and Dsg3, when injected into neonatal mice, induce the BP, PF, and PV disease phenotypes, respectively. We found that FcRn-deficient mice were resistant to experimental BP, PF, and PV. Circulating levels of pathogenic IgG in FcRndeficient mice were significantly reduced compared with those in WT mice. Administration of high-dose human IgG (HDIG) to WT mice also drastically reduced circulating pathogenic IgG levels and prevented blistering. In FcRn-deficient mice, no additional protective effect with HDIG was realized. These data demonstrate that the therapeutic efficacy of HDIG treatment in the pemphigus and pemphigoid models is dependent on FcRn. Thus, FcRn is a promising therapeutic target for treating such IgG-mediated autoimmune diseases.

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“…This effect has in many cases been ascribed to the lowering of autoantibody titres. In some autoimmune diseases such as myasthenia gravis, the effective use of IVIG has been favourably compared with plasmapheresis in treating the chronic phase of the disease [41,42]. In patients with PBC, antimitochondrial antibodies persist after liver transplantation, and recurrence of histological PBC in the allografted liver, although a rare occurrence [43], has been reported [44].…”

Section: Discussionmentioning

confidence: 99%

Reduction in serum levels of antimitochondrial (M2) antibodies following immunoglobulin therapy in severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from patients with primary biliary cirrhosis (PBC)

Abedi¹,

Hammarström

Broomé³

et al. 1996

Clinical and Experimental Immunology

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The effect of gammaglobulin treatment on autoantibody production was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC) obtained from patients with PBC. All reconstituted mice displayed the presence of human antimitochondrial antibodies (αM2Ab) of both IgG and IgM types before treatment with human immunoglobulin. Two weeks after i.p. injection of 20 ×106 PBMC into SCID mice, i.p. treatment with various preparations of human immunoglobulin was initiated. In control animals treated with saline, serum levels of human αM2Ab of the IgG type increased with time, peaking around 4 weeks after reconstitution. In contrast, human IgG autoantibodies rapidly decreased in all animals treated with human IgG. Treatment with a human IgM preparation had no effect on serum levels of αM2Ab of the IgG type. The results may suggest that the pronounced reduction of specific IgG autoantibodies was due to an increased catabolism of human IgG, including the autoantibodies, in the gammaglobulin‐treated mice. Although the production of human αM2Ab in reconstituted mice could be easily shown, PBC‐specific liver lesions or bile duct destruction were not observed, irrespective of treatment protocol.

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High-Dose Intravenous Gammaglobulin for Myasthenia Gravis

Cited by 160 publications

References 4 publications

Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG

Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG

Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases

Reduction in serum levels of antimitochondrial (M2) antibodies following immunoglobulin therapy in severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from patients with primary biliary cirrhosis (PBC)

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