A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency

Eur J Haematol. 2007 Oct;79(4):338-48. doi: 10.1111/j.1600-0609.2007.00927.x. Epub 2007 Aug 3.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / administration & dosage*
  • Adenosine Deaminase / deficiency*
  • Adenosine Deaminase / immunology
  • Adenosylhomocysteinase / immunology
  • Adenosylhomocysteinase / metabolism
  • Adult
  • Antigens, CD20 / blood
  • Antigens, CD20 / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Deoxyadenine Nucleotides / immunology
  • Deoxyadenine Nucleotides / metabolism
  • Enzymes, Immobilized / administration & dosage*
  • Erythrocytes / enzymology
  • Erythrocytes / immunology
  • Female
  • Forced Expiratory Flow Rates / drug effects
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Lung Diseases / enzymology
  • Lung Diseases / immunology
  • Lung Diseases / physiopathology
  • Lymphocyte Count
  • Polyethylene Glycols / administration & dosage
  • Severe Combined Immunodeficiency / drug therapy*
  • Severe Combined Immunodeficiency / enzymology*
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / physiopathology
  • Time Factors


  • Antigens, CD20
  • Autoantibodies
  • Deoxyadenine Nucleotides
  • Enzymes, Immobilized
  • Immunoglobulin G
  • Polyethylene Glycols
  • Adenosylhomocysteinase
  • Adenosine Deaminase