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עמוד בית
Sat, 07.12.24

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January 2008
S. Fuchs, T. Feferman, R. Meidler, T. Brenner, O. Laub and M.C. Souroujon

Backgraound: Intravenous immunoglobulin administration has been beneficially used for the treatment of a variety of autoimmune diseases including myasthenia gravis, although its mode of action and active components have not yet been fully identified.

Objectives: To isolate from IVIg[1] a disease-specific fraction involved in the therapeutic activity in myasthenia and to identify its properties and function.

Results: IVIg administration in experimental autoimmune MG[2] results in suppression of disease that is accompanied by decreased Th1 cell and B cell proliferation. Chromatography of IVIg on columns of IgG from rats with EAMG[3] or from MG patients resulted in depletion of the suppressive activity that IVIg has on rat EAMG. Moreover, the minute amounts of IgG fractions eluted from the EAMG or MG-specific columns retained the immunosuppressive activity of IVIg.

Conclusions: Our study supports the notion that the therapeutic effect of IVIg is mediated by a minor disease-specific immunoglobulin fraction that is present in IVIg and is essential for its therapeutic activity.





[1] IVIg = inravenous immunoglobulin

[2] MG = myasthenia gravis

[3] EAMG = experimental autoimmune myasthenia gravis 


E. Toubi


Among the several mechanisms that play a role in maintaining peripheral self-tolerance is the existence of a unique CD4+CD25+ population of naturally occurring regulatory T cells, which actively prevent both the activation and the effector function of autoreactive T cells that have escaped different mechanisms of tolerance. Many studies have shown the benefit of targeting this cell population by restoring self-tolerance. Therapies that could possibly increase the suppressive ability of T regulatory cells were proven to improve the course of autoimmune diseases.

April 2002
Tomas Kozak, MD and Ivan Rychlik, MD

Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy, including high dose cytotoxic agents and hematopoietic autologous stem cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that have a rapid course and are resistant to conventional therapy. The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging. The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit of the aggressive approach. A randomized trial involving SSc[1] was recently launched (ASTIS) and a trial involving MS[2] is under preparation. Considerably less experience with immunoablative treatment has been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology. Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies.

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[1] SSc = systemic sclerosis


[2] MS = multiple sclerosis


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