Severe combined immunodeficiencies

Abstract

Severe combined immunodeficiencies (SCID) represent an heterogeneous group of diseases characterized by a profound defect in either T cell differentiation or function. The molecular nature of the defect has so far been defined for a small number of SCID, i.e. purin metabolism enzyme deficiencies. Progress has however been made in either gene localization (i.e. X-linked SCID--characterized by an isolated blockade of T-cell differentiation) or in determining mechanisms underlying SCID (i.e. abnormal T cell receptor and immunoglobulin gene rearrangements in alymphocytosis, defective signal transduction in some atypical SCID with non functional T cells or membrane abnormalities such as low expression of the T cell receptor/CD3 complex or defective expression of MHC Class II molecules). Significant improvement in the therapy of SCIDs has been made in the last 10 years leading to cure of at least 3/4 patients with SCID by either HLA identical or non identical bone marrow transplantation. Alternative therapy has been proposed for adenosine deaminase (ADA) deficiency enzyme substitution by polyethylene glycol-ADA. The prospect of gene therapy for this disease and potentially for other types SCIDs is forthcoming.