Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment.
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.
Bozzi
F
F
Department of Paediatrics, University of Brescia, Italy.
Lefranc
G
G
Villa
A
A
Badolato
R
R
Schumacher
R F
RF
Khalil
G
G
Loiselet
J
J
Bresciani
S
S
O'Shea
J J
JJ
Vezzoni
P
P
Notarangelo
L D
LD
Candotti
F
F
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
D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3