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

Bax, BE; Bain, MD; Fairbanks, LD; Webster, AD; Ind, PW; Hershfield, MS; Chalmers, RA (2007) A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency. EUROPEAN JOURNAL OF HAEMATOLOGY, 79 (4). 338 - 348. ISSN 0902-4441 https://doi.org/10.1111/j.1600-0609.2007.00927.x
SGUL Authors: Bax, Bridget Elizabeth

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Abstract

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 lmol ⁄ 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.

Item Type: Article
Additional Information: This is the accepted version of the following article: Bax, B. E., Bain, M. D., Fairbanks, L. D., Webster, A. D. B., Ind, P. W., Hershfield, M. S. and Chalmers, R. A. (2007), A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency. European Journal of Haematology, 79: 338–348. doi: 10.1111/j.1600-0609.2007.00927.x, which has been published in final form at http://dx.doi.org/10.1111/j.1600-0609.2007.00927.x
Keywords: Adenosine Deaminase, Adenosylhomocysteinase, Adult, Antigens, CD20, Autoantibodies, Deoxyadenine Nucleotides, Enzymes, Immobilized, Erythrocytes, Female, Forced Expiratory Flow Rates, Humans, Immunoglobulin G, Lung Diseases, Lymphocyte Count, Polyethylene Glycols, Severe Combined Immunodeficiency, Time Factors, Science & Technology, Life Sciences & Biomedicine, Hematology, adenosine deaminase deficiency, carrier erythrocytes, drug delivery systems, enzyme replacement therapy, severe combined immunodeficiency disease, erythrocytes, SEVERE COMBINED IMMUNODEFICIENCY, BONE-MARROW-TRANSPLANTATION, THYMIC OUTPUT, GENE-THERAPY, IN-VIVO, ABNORMALITIES, AGE
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: EUROPEAN JOURNAL OF HAEMATOLOGY
ISSN: 0902-4441
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Dates:
DateEvent
1 October 2007Published
Web of Science ID: WOS:000249428100011
URI: http://openaccess.sgul.ac.uk/id/eprint/100455
Publisher's version: https://doi.org/10.1111/j.1600-0609.2007.00927.x

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