Induction of myasthenia gravis, myositis, and insulin-dependent diabetes mellitus by high-dose interleukin-2 in a patient with renal cell cancer

J Immunother. Jul-Aug 2002;25(4):373-8. doi: 10.1097/00002371-200207000-00009.

Abstract

Interleukin-2 is an effective agent against renal cell carcinoma and melanoma, but it has been associated with autoimmune sequelae such as hypothyroidism and vitiligo. A 64-year-old man with non-insulin-dependent diabetes and metastatic renal cell carcinoma developed insulin-dependent diabetes after his first cycle of therapy with high-dose (HD) interleukin-2. After additional therapy with interleukin-2, the patient developed generalized myasthenia gravis (MG) and polymyositis, both of which responded to treatment with corticosteroids and plasmapheresis. To investigate the role of IL-2 in the development of these autoimmune complications, autoantibody titers were assayed from serum obtained before and after IL-2 treatment and after treatment with corticosteroids plus plasmapheresis. Before IL-2 treatment, the patient had antibodies directed against insulin, islet cell antigens, and striated muscle. Acetylcholine receptor antibody levels were normal before starting IL-2. After treatment with IL-2, the patient developed acetylcholine receptor binding antibodies and exhibited an increase in the striated muscle antibody titer from 1:40 to 1:160. Recovery from the MG and polymyositis was associated with substantial decreases in the acetylcholine receptor and striated muscle antibody titers. These findings suggest that HD IL-2 accelerated the progression of latent autoimmune diabetes and myositis in this patient whose tolerance to islet cell antigens and striated muscle had already been broken and precipitated a break in tolerance to the acetylcholine receptor resulting in the development of MG. This case demonstrates the importance of prompt recognition of IL-2-induced MG and shows how this complication can be successfully managed with aggressive therapy.

Publication types

  • Case Reports
  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Carcinoma, Renal Cell / complications*
  • Carcinoma, Renal Cell / drug therapy
  • Diabetes Mellitus, Type 1 / chemically induced*
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-2 / adverse effects*
  • Interleukin-2 / therapeutic use
  • Kidney Neoplasms / complications*
  • Kidney Neoplasms / drug therapy
  • Lung Neoplasms / complications*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Myasthenia Gravis / chemically induced*
  • Myositis / chemically induced*

Substances

  • Interleukin-2