Immunotherapy of type I diabetes.

A recent NIH panel in which I participated unanimously agreed that wide clinical application of immunotherapy for type I diabetes is at present inappropriate. The risks of premature application of such therapy outweigh potential benefits. In this editorial, I will briefly review the current information upon which I and my colleagues have begun small research trials of immunotherapy which 1 believe are essential for the eventual development of therapy to prevent type I diabetes. An issue in considerations of immunotherapy in man is whether an acute viral-induced diabetes occurs which im-munotherapy may worsen. The existence of acute viral-induced diabetes is a controversial area despite years of research. I suspect that if acute virally induced diabetes occurs, it is extremely rare, and even the best documented case of Dr. Notkins and co-workers appears not to have been acute.' Dr. Gepts, studying sections of the pancreas of the child from which the virus was isolated, reported finding signs of chronic beta-cell damage (the pancreas contained multiple "pseudoatrophic" islets with no inflammation and only non-beta islet cells remaining). 2 Despite little evidence of an acute viral etiology for diabetes, viruses and perhaps other environmental factors may play a major role in initiating an autoimmune process in a genetically susceptible host. A very high percentage of DR3/DR4 positive children with congenital rubella in later life develop diabetes. 3 If type I diabetes is not an acute viral illness, is it an autoimmune disease? [By an autoimmune disease I refer to tissue destruction, which is created by lymphocytes (T-or B-cells) reacting with self antigens.] The autoimmune hypothesis has been reviewed many times and though current data are convincing, it should be emphasized that the hypothesis that type I diabetes of humans is an autoimmune disease is not proven. In contrast, the diabetes of the BB rat is a proven genetically determined autoimmune disease with no defined viral or environmental etiologic factors. 4 More than seven forms of immunotherapy can prevent these animals from developing diabetes and one form (anti-lympho-cyte serum) can "cure" one-third of these animals. 5 ' 6 Though the BB rat is an important animal model of type I diabetes, these animals are fundamentally different from patients with type I diabetes in that they inherit a profound T-cell im-munodeficiency that is necessary but not sufficient for the development of diabetes. 7 These animals are equivalent to a child with severe immunodeficiency (e.g., adenosine …