Janus kinase 3 deficiency

JAK3 (Janus kinase 3) deficiency is a dysfunction in cytokine receptor signalling and their production of cytokines.

JAK3 is a tyrosine protein kinase, an enzyme that is encoded by the JAK3 gene. It is a kinase that is activated only by cytokines whose receptors contain the common gamma chain subunit (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21). JAK3 is involved in iniating signalling for the cytokine receptors because they itself lack enzymatic activity. Once activated, the JAK kinase phosphorylates specific tyrosine residues on the cytokine receptor subunits which then activate STAT transcription factors. JAK3 helps to regulate differentiation and maturation of B cells, T cells and NK cells.

Mutations in the JAK3 gene can cause dysfunction of the kinase leading to autosomal severe combined immunodeficiency (SCID) disease [1] or on the contrary, the activation of mutated JAK3 can lead to development of leukemia. The JAK3 tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases.[2]

Patients with JAK3-deficiency lack the necessary immune cells, meaning that they do not have T cells and NK cells but have normal level but poorly functioning B cells. The necessary immune cells have resistance and ability to fight off certain bacteria, viruses, and fungi. The patients are then prone to repeated and persistent infections that can be very serious or life-threatening.[3]

Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush (candidiasis), pneumonia, and skin rashes. Constant illness also causes slower development of the affected individuals. Without treatment, people with JAK3-deficient SCID usually live only into early childhood.[3]