Correct!
3. STAT3 signal transduction

In 2007 an autosomal dominant mutation in signal transducer and activator of transcription factor 3 (STAT3) was identified as the link for infections and connective tissue abnormalities. STAT3 is integral to signal transduction for multiple cytokines (some pro-inflammatory, some anti-inflammatory) and mutations in STAT3 are generally regarded as the cause of HIES (1). Abnormalities in STAT3 result in failure of Th17 CD4 cell differentiation and a defect in neutrophil migration (chemotaxis) contributing to the increased risk of infection.

Patients with HIES usually present with skin infections/skin rashes early in life; mucocutaneous candidiasis; recurrent sinopulmonary infections with aberrant healing; bronchiectasis; and pneumatoceles. There is an increased risk of malignancies – most often non-Hodgkin’s lymphoma, but others have been reported. There is also an increased incidence of vascular abnormalities.

Treatment of HIES includes proper skin care; aggressive treatment of infections; and prophylactic antibiotics may be appropriate in some patients (1). Bone marrow transplantation has been performed in a few patients with improvement reported (1).

Reference

  1. Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann NY Acad Sci. 2012;1250:25-32. [CrossRef] [PubMed]

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