Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID).
Adenosine deaminase (ADA)-deficient Severe Combined Immunodeficiency (ADA-deficient SCID) is characterized by impaired lymphocyte development and function resulting from the adenosine metabolism defect. Enzyme replacement therapy with polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) minimizes infectious complications of ADA-deficient patients who have not received bone marrow transplantation. In PEG-ADA therapy, enzymatically active ADA continuously circulates to act as a metabolic sink, detoxifying the adenosine and deoxyadenosine metabolites that accumulate to high levels in the absence of ADA. Studies have shown that upon the initiation of PEG-ADA therapy, the absolute numbers of circulating T and B lymphocytes and NK cells increase and protective immune function develops. However, the long-term efficacy is unknown. This retrospective study was designed to assess the long-term effectiveness of PEG-ADA treatment, based on evaluation of the immune function of nine ADA-deficient SCID patients (age 5-15) treated over the past decade. The results showed that the lymphocyte counts of all of the PEG-ADA treated patients were below the normal range at all times, despite initial improvements. A gradual decline of mitogenic proliferative responses occurred after a few years of treatment and normal antigenic response occurred less than expected. To this date, these low numbers and functions of lymphocytes had been adequate to provide protective immunity. These patients should be followed closely to detect a premature decline in immune function with aging in future decades of PEG-ADA therapy.
Chan
Belinda
B
Division of Research Immunology/B.M.T., Mailstop number 62, Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, 4650 Sunset Blvd, Los Angeles, CA 90027, USA.
Wara
Diane
D
Bastian
John
J
Hershfield
Michael S
MS
Bohnsack
John
J
Azen
Colleen G
CG
Parkman
Robertson
R
Weinberg
Kenneth
K
Kohn
Donald B
DB
D000243:Adenosine Deaminase / Q000172:deficiency* / Q000627:therapeutic use*; D000293:Adolescent; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D007136:Immunoglobulins; D000243:Adenosine Deaminase; C051409:pegademase bovine