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 (γc) or of γc 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 γc-JAK3 signalling pathway is not strictly required for immunoglobulin production.