Severe combined immunodeficiency (SCID) with JAK3 deficiency
- Fabio Candotti, MD
Fabio Candotti, MD
- Associate Professor
- University Hospital of Lausanne (CHUV)
- Luigi D Notarangelo, MD
Luigi D Notarangelo, MD
- Section Editor — Immunology and Immunodeficiency
- Bethesda, MD
Genetic mutations affecting the gamma chain of the interleukin-2 (IL-2) receptor and the associated downstream signaling enzyme Janus kinase 3 (JAK3) result in T cell negative, B cell positive, natural killer (NK) cell negative severe combined immunodeficiency (T-B+NK- SCID) (table 1 and figure 1). Defects of the JAK3 gene result in a type of T-B+NK- SCID that is transmitted via an autosomal recessive mode of inheritance (MIM #600802) [1-3].
Patients with SCID due to JAK3 deficiency typically present at a few months of age with classical clinical features of SCID, including recurrent or severe respiratory infections, intractable diarrhea, thrush, and failure to thrive [1-6]. (See "Severe combined immunodeficiency (SCID): An overview", section on 'Clinical manifestations'.)
The pathogenesis, clinical features, diagnosis, and treatment of T-B+NK- SCID with JAK3 deficiency are presented in this topic review. An overview of the different forms of SCID can be found separately. (See "Severe combined immunodeficiency (SCID): An overview" and "Severe combined immunodeficiency (SCID): Specific defects".)
Signal transduction by the hematopoietic cytokines, interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21, is of critical importance for the development and function of the cells of the immune system [9,10]. Cellular receptors for all these cytokines share the "common" gamma chain (gamma-c) [11-19] that lacks intrinsic catalytic activity, but mediates signal transduction via its physical association with a member of the Janus family of protein kinases (JAK), JAK3 [16,20].
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