also improved but was variable from time to time in a given patient. Total serum 
immunoglobulin levels also increased in those patients not already on IV gammaglobulin 
replacement therapy. These improved laboratory parameters have persisted with continued 
PEG-ADA injections and have been associated with an apparent decrease in the frequency of 
serious “opportunistic infections”; in addition, accelerated weight gain has been seen in some 
patients. However, evidence of total immune system reconstitution has not been seen. Many 
have not developed positive delayed type hypersensitivity skin reactions and several have been 
unable to produce specific antibodies to tetanus toxoid or other commonly tested antigens. Two 
children on PEG-ADA treatment have developed anti PEG-ADA neutralizing antibody which 
interfered with the treatment. Paradoxically this problem was reversed following 
administration of a course of immunosuppressive therapy to one immunodeficient child (70). 
One of the ironies associated with the use of PEG-ADA in the treatment of ADA(-)SCID is that 
the modest increase jn immune function achieved with this treatment suggests that a bone 
marrow transplantation from a haploidenticai (ie., parental) donor without 
immunosuppression/cytoablation would fail because of graft rejection. Any transplant in this 
setting then would probably require full cytoreductive immunosuppressive conditioning with 
its attendant increased risk of complications or alternatively exposure to a period of withdrawal 
of PEG-ADA treatment to allow the condition of the immune system to deteriorate. 
There are insufficient data to fully evaluate the long term value of PEG-ADA therapy, although 
its use does not provide a cure for this disease. It appears that in many cases, enzyme 
replacement converts severe combined immunodeficiency disease (SCID) to a disorder more 
closely resembling a partial combined immunodeficiency disorder (like the Wiskott-Aldrich 
syndrome). Without restoration of the capacity to develop a full range of normal specific 
immune responses, children with partial combined immunodeficiencies continue to be at 
increased risk of bacterial, fungal and viral infections, the development of autoimmune 
phenomena, and an increased risk of malignancy{49). Therefore, alternatives or additions to 
PEG-ADA therapy need to be developed. 
Several alternatives to transplantation are under study in patients with ADA(+)SCID. In 
patients whose lymphocytes in culture demonstrate response to supplementation with IL-2, a 
trial of daily parenteral injections of IL2 has resulted in some evidence of clinical stabilization 
and enhanced immune function(50-52). Because of the inconvenience and discomfort of daily 
IL-2 injections, a new protocol using a longer acting and possibly less toxic PEG-IL2 
Recombinant DNA Research, Volume 14 
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