STAT3 Mutations are a Newly Recognized Genetic Cause of Hyper-IgE Syndrome

Hyper-IgE syndrome (Job's syndrome), first described in 1961, is a rare immunodeficiency disorder characterized by:

- extremely elevated IgE levels
- pneumonias which lead to pneumatoceles
- recurrent cold staphylococcal abscesses
- dermatitis
- retained primary dentition
- and bone abnormalities

Many patients with autosomal dominant hyper-IgE syndrome (HIES) fail to lose their baby teeth and have two sets of teeth simultaneously. HIES was first described by Davis et al. in 1966 in two girls with chronic dermatitis, recurrent staphylococcal abscesses and pneumonias. They named the disease after the biblical character Job, whose body was covered with boils by Satan.

HIES inheritance is autosomal dominant but sporadic cases also occur.

A recent study published in the NEJM suggest that mutations in STAT3 underlie hyper-IgE immunodeficiency syndrome. STAT3 is an abbreviation for Signal Transducer and Activator of Transcription 3 gene (STAT3).

In conclusion, STAT3 mutations are a newly recognized genetic cause of hyper-IgE syndrome.

The discovery of the genetic cause will hopefully lead to better understanding of organ-specific infections and effective therapy in the future.


Cytokine Signaling. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

References:

STAT3 Mutations in the Hyper-IgE Syndrome. NEJM, 10.1056/NEJMoa073687, 09/2007.
Hyperimmunoglobulinemia E (Job) Syndrome. eMedicine.
Hyper IgE Syndrome: An Update on Clinical Aspects and the Role of Signal Transducer and Activator of Transcription 3.
Michelle L. Paulson; Alexandra F. Freeman; Steven M. Holland. Current Opinion in Allergy and Clinical Immunology, Medscape, 2008.
Job Syndrome. eMedicine.
Cutaneous Manifestations of Hyper IgE Syndrome (full text PDF) and http://goo.gl/uJWMT
Hyper-IgE syndrome, from Wikipedia, the free encyclopedia.