A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency.
Adenosine deaminase (ADA) deficiency is an inherited disorder which leads to elevated cellular levels of deoxyadenosine triphosphate (dATP) and systemic accumulation of its precursor, 2-deoxyadenosine. These metabolites impair lymphocyte function, and inactivate S-adenosylhomocysteine hydrolase (SAHH) respectively, leading to severe immunodeficiency. Enzyme replacement therapy with polyethylene glycol-conjugated ADA is available, but its efficacy is reduced by anti-ADA neutralising antibody formation. We report here carrier erythrocyte encapsulated native ADA therapy in an adult-type ADA deficient patient. Encapsulated enzyme is protected from antigenic responses and therapeutic activities are sustained. ADA-loaded autologous carrier erythrocytes were prepared using a hypo-osmotic dialysis procedure. Over a 9-yr period 225 treatment cycles were administered at 2-3 weekly intervals. Therapeutic efficacy was determined by monitoring immunological and metabolic parameters. After 9 yr of therapy, erythrocyte dATP concentration ranged between 24 and 44 micromol/L (diagnosis, 234) and SAHH activity between 1.69 and 2.29 nmol/h/mg haemoglobin (diagnosis, 0.34). Erythrocyte ADA activities were above the reference range of 40-100 nmol/h/mg haemoglobin (0 at diagnosis). Initial increases in absolute lymphocyte counts were not sustained; however, despite subnormal circulating CD20(+) cell numbers, serum immunoglobulin levels were normal. The patient tolerated the treatment well. The frequency of respiratory problems was reduced and the decline in the forced expiratory volume in 1 s and vital capacity reduced compared with the 4 yr preceding carrier erythrocyte therapy. Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective.
Child Health, Division of Clinical Developmental Sciences, St George's, University of London, London, UK. bebax@sgul.ac.uk
Bridget E
BE
Bax
Murray D
MD
Bain
Lynette D
LD
Fairbanks
A David B
AD
Webster
Philip W
PW
Ind
Michael S
MS
Hershfield
Ronald A
RA
Chalmers
D000243:Adenosine Deaminase / Q000008:administration & dosage* / Q000172:deficiency* / Q000276:immunology; D043383:Adenosylhomocysteinase / Q000276:immunology / Q000378:metabolism; D000328:Adult; D018951:Antigens, CD20 / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D003838:Deoxyadenine Nucleotides / Q000276:immunology / Q000378:metabolism; D004800:Enzymes, Immobilized / Q000008:administration & dosage*; D004912:Erythrocytes / Q000201:enzymology / Q000276:immunology; D005260:Female; D005540:Forced Expiratory Flow Rates / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008171:Lung Diseases / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D018655:Lymphocyte Count; D011092:Polyethylene Glycols / Q000008:administration & dosage; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D013997:Time Factors
D018951:Antigens, CD20; D001323:Autoantibodies; D003838:Deoxyadenine Nucleotides; D004800:Enzymes, Immobilized; D007074:Immunoglobulin G; D011092:Polyethylene Glycols; D043383:Adenosylhomocysteinase; D000243:Adenosine Deaminase