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 im munodeficiency (SCID) developed resistance to therapeutic injections o f bovine ADA conjugated to polyethylene glycol (PEG-ADA). This 18-year -old girl was diagnosed as having partial ADA deficiency at age 7 year s, and was started on bovine conjugated PEG-ADA at age 15 years. The w eekly dose of 15 U/kg led to clinical improvement with resolution of s inusitis and bronchitis within 2 months and normalization of some T ce ll functions. After 5 months, however, she developed an inhibitory ant ibody to ADA, became refractory to treatment with PEG-ADA, and clinica lly and immunologically deteriorated. This antibody was successfully s uppressed 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 r estarted at a higher dose (20 U/kg/dose, twice a week). With the suppr ession 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-A DA (20 U/kg/week) with sustained clinical and immunologic improvement, including weakly positive antigen-specific T cell proliferative respo nses to tetanus and Candida.