title: Increased radiosensitivity of granulocyte macrophage colony-forming units and skin fibroblasts in human autosomal recessive severe combined immunodeficiency.
abstract: We studied the radiosensitivity of granulocyte macrophage colony-forming units (GM-CFU) in patients with a severe combined immunodeficiency (SCID). Three patients lacking both mature T and B cells showed a twofold higher GM-CFU radiosensitivity calculated as the DO value (dose required to reduce survival to 37%), and an identical observation was made with fibroblasts from one of these patients. A patient with an SCID with hypereosinophilia, i.e., Omenn's syndrome characterized by extremely restricted T cell heterogeneity and a lack of B cells, also showed abnormal GM-CFU radiosensitivity. In contrast, GM-CFU from a patient lacking only T cells (X-linked form of SCID) showed normal GM-CFU radiosensitivity. These data further support the similarity between human T(-) B(-) SCID and the murine acid mutation characterized by a defect in T cell receptor and immunoglobulin gene rearrangement, and by an abnormal double-strand DNA break repair function. In addition, they strongly suggest that the Omenn's immunodeficiency syndrome may be a leaky T(-)B(-) SCID phenotype as previously indicated by the coexistence of the two phenotypes in siblings.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 132, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: G
authors.initials: G
authors.lastname: De Saint Basile
authors.forename: D
authors.initials: D
authors.lastname: Papadopoulo
authors.forename: J P
authors.initials: JP
authors.lastname: De Villartay
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D005808:Genes, Recessive; D006098:Granulocytes / Q000473:pathology / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D007223:Infant; D008264:Macrophages / Q000473:pathology / Q000528:radiation effects; D008297:Male; D012016:Reference Values; D015183:Restriction Mapping; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D004247:DNA