title: Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment.
abstract: Severe combined immunodeficiency (SCID) comprises a heterogenous group of disorders that are fatal unless treated by bone marrow transplantation (BMT). The most common form of SCID (T-B+ SCID) is due to mutations of either the common gamma chain (gammac) or of gammac-coupled JAK3 kinase. We report an unusual JAK3 defect in a female who was successfully treated > 20 years ago with a BMT using her HLA-identical father as the donor. Persistence of genetically and biochemically defective autologous B cells, associated with reconstitution of cellular and humoral immunity, suggests that integrity of the gammac-JAK3 signalling pathway is not strictly required for immunoglobulin production.
authors.affiliation: Department of Paediatrics, University of Brescia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bozzi
authors.forename: G
authors.initials: G
authors.lastname: Lefranc
authors.forename: A
authors.initials: A
authors.lastname: Villa
authors.forename: R
authors.initials: R
authors.lastname: Badolato
authors.forename: R F
authors.initials: RF
authors.lastname: Schumacher
authors.forename: G
authors.initials: G
authors.lastname: Khalil
authors.forename: J
authors.initials: J
authors.lastname: Loiselet
authors.forename: S
authors.initials: S
authors.lastname: Bresciani
authors.forename: J J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: P
authors.initials: P
authors.lastname: Vezzoni
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: F
authors.initials: F
authors.lastname: Candotti
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D015153:Blotting, Western; D016026:Bone Marrow Transplantation / Q000379:methods; D005260:Female; D017353:Gene Deletion; D006801:Humans; D053616:Janus Kinase 3; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3