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.
Bax
Bridget E
BE
Child Health, Division of Clinical Developmental Sciences, St George's, University of London, London, UK. bebax@sgul.ac.uk
Bain
Murray D
MD
Fairbanks
Lynette D
LD
Webster
A David B
AD
Ind
Philip W
PW
Hershfield
Michael S
MS
Chalmers
Ronald A
RA
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