Interleukin-2 Treatment for Wiskott-Aldrich Syndrome

The Wiskott-Aldrich syndrome (WAS) is a fatal genetic disease of the immune system that results from a mutation of the WAS protein (WASp) gene. Immune cells that carry this mutation have a decreased ability to reorganize filamentous actin (F-actin) after activation. As a result there are a number of defective immunologic functions, some of which result in deficient host defense. The investigators have identified a pervasive deficit in natural killer (NK) cell cytotoxicity in WAS patients. WAS patients suffer from conditions that are hallmarks of NK cell deficiencies. These include severe herpesvirus infections and B cell malignancies. Our lab and others have also found that exposure of WAS subject NK cells to IL-2 in vitro restores NK cell function and allows for normal F-actin reorganization. Thus, the investigators propose a proof of principal clinical trial to treat WAS subjects with IL-2 to determine safety and efficacy of IL-2 in this population and if NK cell function is restored ex vivo. If IL-2 can circumvent a defective WASp to restore NK cell function, the investigators will propose a larger NIH funded efficacy trial of IL-2 in WAS. The investigators will also use the in vivo treatment of WAS subjects to forward our mechanistic studies of how IL-2 may facilitate F-actin reorganization in the absence of WASp function.

Inclusion criteria

• Age: Subjects age greater than 24 months
• Weight: Subjects greater than 12.5 kilograms
• Disease status: WAS classified as Grade 1-4
• Informed Consent: Written informed consent of the subject (if an adult) or parental permission, and assent of the child subject provided justification is made for the inclusion of children in the study

Exclusion criteria

• Prior or planned hematopoetic transplant
• WAS classified as currently Grade 5 (Malignancy or autoimmune disease including the following: Crohn's disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome and bullous pemphigoid . Not included here are: Hepatitis C virus induced vasculitis, alopecia areata and systemic lupus erythematosus.)
• Known previous reaction to IL-2
• Subjects taking immunosuppressive medications that might alter study results
• Subjects taking nephrotoxic, cytotoxic, cardiotoxic, or hepatotoxic medications (including medications for hypertension)
• Subjects currently taking systemic corticosteroids (not included here: topical and inhaled corticosteroids)
• Subjects taking Interferon alpha
• Use of any other investigational agent in the last 30 days
• Women of childbearing potential not using contraception method(s), as well as women who are breastfeeding
• Subjects with abnormal cardiac, hepatic and CNS function