Suppression of an antibody to adenosine-deaminase (ADA) in an ADA-deficient patient receiving polyethylene glycol modified adenosine deaminase.

An adenosine deaminase (ADA) deficient patient with severe combined immunodeficiency (SCID) developed resistance to therapeutic injections of bovine ADA conjugated to polyethylene glycol (PEG-ADA). This 18-year-old girl was diagnosed as having partial ADA deficiency at age 7 years, and was started on bovine conjugated PEG-ADA at age 15 years. The weekly dose of 15 U/kg led to clinical improvement with resolution of sinusitis and bronchitis within 2 months and normalization of some T cell functions. After 5 months, however, she developed an inhibitory antibody to ADA, became refractory to treatment with PEG-ADA, and clinically and immunologically deteriorated. This antibody was successfully suppressed over a 4-month period with a combination of prednisone (2 mg/kg/day), intravenous immunoglobulin (2 g/kg/dose), and discontinuing the PEG-ADA injections for 7 weeks. The PEG-ADA injections were then restarted at a higher dose (20 U/kg/dose, twice a week). With the suppression of the inhibitory antibody, her clinical and immunologic status improved to previously achieved level. She has subsequently continued treatment for over 36 months, receiving a single weekly dose of PEG-ADA (20 U/kg/week) with sustained clinical and immunologic improvement, including weakly positive antigen-specific T cell proliferative responses to tetanus and Candida.

Duke Scholars

Author Michael Steven Hershfield Medicine, Rheumatology and Immunology