Immunodeficiency: Severe Combined Immunodeficiency Disease

Abstract

Severe combined immunodeficiency disease (SCID) is defined as (1) absence or very low number of T cells (<300 CD3+ T cells/mm3) and no or very low T‐cell function (<10% of lower limit of normal) as measured by response to phytohaemagglutinin or (2) presence of T cells of maternal origin. It has an incidence of approximately 1 per every 58 000 live births. SCID is caused by defects in at least 16 different genes, each of which results in failure to produce functional host‐derived T cells through various pathogenic mechanisms. Improved understanding of these fundamental processes has led to significant advances in the diagnosis, management and definitive treatment of individuals with this life‐threatening condition.

Key Concepts

  • Severe combined immunodeficiency disease is defined by a congenital lack of functional T cells, resulting in death from infections by 1–2 years of age.
  • Many molecular defects underlying SCID have been identified, yielding valuable insights regarding immune biology.
  • Diagnosis has been enhanced by newborn screening, resulting in successful treatment of affected infants.
  • Definitive therapy options include haematopoietic stem cell transplantation and gene therapy, the latter of which has shown promise and remains actively investigated.
  • Optimal outcomes have been associated with definitive treatment before 3.5 months of age and onset of active infections.

Keywords: T cell; cytokine; thymus; TREC; V(D)J recombination; T cell receptor; haematopoietic stem cell transplantation; gene therapy

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Further Reading

Chan K and Puck JM (2005) Development of population‐based newborn screening for severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 115 (2): 391–398.

Dvorak CC and Cowan MJ (2010) Radiosensitive severe combined immunodeficiency disease. Immunology and Allergy Clinics of North America 30 (1): 125–142.

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Horn B and Cowan MJ (2013) Unresolved issues in hematopoietic stem cell transplantation for severe combined immunodeficiency: need for safer conditioning and reduced late effects. Journal of Allergy and Clinical Immunology 131 (5): 1306–1311.

Meuwissen HJ, Gatti RA, Terasaki PI, Hong R and Good RA (1969) Treatment of lymphopenic hypogammaglobulinemia and bone‐marrow aplasia by transplantation of allogeneic marrow. New England Journal of Medicine 281 (13): 691–697.

Omenn GS (1965) Familial Reticuloendotheliosis with Eosinophilia. New England Journal of Medicine 273 (8): 427–432.

Shearer WT, Fleisher TA, Buckley RH, et al. (2014) Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. Journal of Allergy and Clinical Immunology 133 (4): 961–966.

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Chinn, Ivan K, and Shearer, William T(Nov 2016) Immunodeficiency: Severe Combined Immunodeficiency Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001458.pub2]