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Severe combined immunodeficiency (SCID) with JAK3 deficiency

Authors
Fabio Candotti, MD
Luigi D Notarangelo, MD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

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".)

EPIDEMIOLOGY

SCID due to JAK3 deficiency is rare, accounting for only about 6 percent of all cases of SCID [3,7] and approximately 1 percent of all cases of immunodeficiency of known genetic origin [8].

PATHOGENESIS

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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Literature review current through: Nov 2016. | This topic last updated: Thu Feb 05 00:00:00 GMT+00:00 2015.
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