JAK3-deficient severe combined immunodeficiency

Genetic mutations affecting JAK3 expression or function result in autosomal recessive SCID. Children affected with JAK3-deficient SCID present with vi rtual absence of T lymphocytes and NK cells, whereas B lymphocytes usually are normal or elevated in number but functionally defective. Because of the profound impairment of cellular and humoral immunity, patients with JAK3 d eficiency are exposed to recurrent and life-threatening infections unless i mmune reconstitution is achieved by allogeneic bone marrow transplantation. The identification of JAK3 as a key player in the development of the immun e system in humans has stimulated many studies detailing the biologic chara cteristics of this important molecule, and has opened the way to possible g enetic intervention.