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Non-infectious Lung Disease in Patients with Adenosine Deaminase Deficient Severe Combined Immunodeficiency

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Abstract

Adenosine deaminase deficiency is a disorder of purine metabolism manifesting severe combined immunodeficiency (ADA-SCID) and systemic abnormalities. Increased levels of the substrate deoxyadenosine triphosphate (dATP) lead to immunodeficiency and are associated in a murine model with pulmonary insufficiency. We compared a cohort of patients with ADA-SCID and X-linked SCID and found that despite similar radiological and respiratory findings, positive microbiology is significantly less frequent in ADA-SCID patients (p < 0.0005), suggesting a metabolic pathogenesis for the lung disease. Clinicians should be aware of this possibility and correct metabolic abnormalities either through enzyme replacement or haematopoietic stem cell transplant, in addition to treating infectious complications.

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Fig. 1

Abbreviations

(ADA-SCID):

Adenosine deaminase deficient severe combined immunodeficiency

(SCID-X1):

X-Linked severe combined immunodeficiency

(dAdo):

Deoxyadenosine

(Ado):

Adenosine

(dATP):

Deoxyadenosine triphosphate

(HSCT):

Haematopoietic stem cell transplant

(ERT):

Enzyme replacement therapy

(RSV):

Respiratory syncytial virus

(NPA):

Nasopharyngeal aspirate

(BAL):

Broncheoalveolar lavage

(MSD):

Matched sibling donor

(MFD):

Matched family donor

(MUD):

Matched unrelated donor

(MMUD):

Mismatched unrelated donor

(CMV):

Cytomegalovirus

(PCP):

Pneumocystis jirovecii

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Authors and Affiliations

  1. Centre of Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    C. Booth & H. B. Gaspar

  2. Department of Clinical Immunology, Great Ormond Street Hospital National Health Service Trust, London, UK

    C. Booth, V. E. Algar, J. Xu-Bayford & H. B. Gaspar

  3. Purine Research Laboratory, Guy’s and St. Thomas’s NHS Trust, London, UK

    L. Fairbanks

  4. Department of Radiology, Great Ormond Street Hospital National Health Service Trust, London, UK

    C. Owens

Authors
  1. C. Booth
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  2. V. E. Algar
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  3. J. Xu-Bayford
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  4. L. Fairbanks
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  5. C. Owens
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  6. H. B. Gaspar
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Corresponding author

Correspondence to H. B. Gaspar.

Additional information

Contributor’s statement: CB collected and analysed data and wrote the manuscript VE collected and analysed data, XBJ, LF and CO contributed data, HBG designed the study and prepared the manuscript.

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Booth, C., Algar, V.E., Xu-Bayford, J. et al. Non-infectious Lung Disease in Patients with Adenosine Deaminase Deficient Severe Combined Immunodeficiency. J Clin Immunol 32, 449–453 (2012). https://doi.org/10.1007/s10875-012-9658-3

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  • DOI: https://doi.org/10.1007/s10875-012-9658-3

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