1. Academic Validation
  2. Severe combined immunodeficiency. A model disease for molecular immunology and therapy

Severe combined immunodeficiency. A model disease for molecular immunology and therapy

  • Immunol Rev. 2005 Feb;203:98-109. doi: 10.1111/j.0105-2896.2005.00223.x.
Alain Fischer 1 Françoise Le Deist Salima Hacein-Bey-Abina Isabelle André-Schmutz Geneviève de Saint Basile Jean-Pierre de Villartay Marina Cavazzana-Calvo
Affiliations

Affiliation

  • 1 INSERM U429, Hôpital Necker-Enfants Malades, Paris, France. alain.fischer@nck.ap-hop-paris.fr
Abstract

Severe combined immunodeficiencies (SCIDs) consist of genetically determined arrest of T-cell differentiation. Ten different molecular defects have now been identified, which all lead to early death in the absence of therapy. Transplantation of allogeneic hematopoietic stem cells (HSCT) can restore T-cell development, thus saving the lives of SCID patients. In this review, the different characteristics of HSCT are discussed along with the available data regarding the long-term outcome. Transient thymopoiesis caused by an exhaustion of donor progenitor cells and possibly a progressive loss of thymus function can lead to a progressive decline in T-cell functions. The preliminary results of gene therapy show the correction of two SCID conditions. Based on the assumption that long-lasting pluripotent progenitor cells are transduced, these data suggest that gene therapy could overcome the long-term recurrence of the T-cell immunodeficiency. SCID is thus a disease model for experimental therapy in the hematopoietic system.

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