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Gegenwärtiger Stand und Zukunft der Immuntherapie des Typ I-Diabetes

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Diabetes mellitus

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Summary

Worldwide efforts in research on the pathogenesis of type I diabetes mellitus have shown that this disease is caused by autoimmunological destruction of pancreatic β 3 cells. The essential part of this destructive process occurs during the prediabetic phase. Based on this knowledge, therapeutic trials with immunosuppressive and immunomodulative substances have been performed within recent years. During the past 5 years numerous trials, for example with plasmapheresis, cortisone, levamisole, ciamexon, nicotinamide, antilymphocyte globulin, γ-globulin, azathioprine and cyclosporin A, have been done. Clear positive results have only been found with the two last-mentioned substances. Remission rates of about 30% – 50% in a Canadian pilot study with cyclosporin A were decisive in leading to two placebo-controlled double-blind studies. In the French cyclosporin A study 122 patients were followed up over a period of 9 months. Dependent on the cyclosporin A blood levels, 37% (>300 ng/ml) or 16.7% (<300 ng/ml) total remissions were observed in the treated group in contrast to 5% in the placebo group. The Canadian-European cyclosporin A study has included 188 patients — 42 in the Viennese Center - whose diagnosis was not older than 6 weeks and in whom the beginning of symptoms was not longer than 14 weeks before. In the cyclosporin A group total remissions were observed ten times more often, depending on the period of symptoms and the beginning of the therapy, than in the placebo group. Comparable side effects were found in both studies: hypertrichosis, gingival hyperplasia, a decline of the creatinine clearance of about 20%, and an increase of the serum creatinine of about 21%. At the moment it is impossible to estimate the degree of chronic nephrotoxicity. Recent studies on kidney biopsies of diabetic children in France who were only treated with a low cyclosporin A dose (blood levels below 350 ng/ml) have not shown any histological changes. These encouraging results of immunological intervention with cyclosporin A justify, further use of this substance in controlled studies — possibly in combination with other immunomodulators — as well as the search for cyclosporin A analogs with fewer renal side effects. We must keep in mind that the immunotherapy used until now represents just a nonspecific immunointervention at the end of a long disease process. The future of immunomodulation in type I diabetes must lie in a primary prevention of the disease, or in a specific immunointervention at a very early stage of the disease. Future studies must reveal whether new applications of immunomodulation such as inhibition of autoantigen expression, inhibition of antigen presentation, elimination of autoreactive T-cell clones or tolerance induction will be a solution. The final goal of this research must be long-term total remission reached using a therapy with few side effects.

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  1. G. Schernthaner
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  1. Medizinische Klinik III und Poliklinik, Klinikum der Justus-Liebig-Universität Gießen, Rodthohl 6, 6300, Gießen, Deutschland

    Reinhard G. Bretzel

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Schernthaner, G. (1990). Gegenwärtiger Stand und Zukunft der Immuntherapie des Typ I-Diabetes. In: Bretzel, R.G. (eds) Diabetes mellitus. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74610-9_3

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  • DOI: https://doi.org/10.1007/978-3-642-74610-9_3

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