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

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.

• Authors: Paula G Fraenkel, Seward B Rutkove, Jean K Matheson, Mary Fowkes, Marie E Cannon, Mary-Elizabeth Patti, Michael B Atkins, Jared A Gollob
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2002 Jul-Aug Vol. 25 Issue 4 Pg. 373-8 ISSN: 1524-9557 [Print] United States
• PMID: 12142560 (Publication Type: Case Reports, Clinical Trial, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Interleukin-2

Topics

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